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At least 955 records · Page 53Linked to original sources
PubMed1991

Leakage of various types of luting agents.

Freshly extracted molar teeth were prepared for complete cast gold crowns cemented with either zinc phosphate cement, polycarboxylate cement, glass ionomer cement, a resin luting agent, or a zinc oxide-eugenol temporary cement. The specimens were tested at 1-, 6-, and 12-month intervals with radioactive 45Ca. The specimens were sectioned, autoradiographs were made, and the marginal leakage was evaluated on a scale of 0 to 3. The results showed that zinc phosphate, polycarboxylate, and glass ionomer cements are equally suited for permanent cementation of restorations. The resin luting agent showed high initial leakage, indicating that it is not as desirable for permanent cementation purposes. The zinc oxide-eugenol cement showed increased leakage with time but is well suited for its indicated purpose, temporary cementation.

Crowns↗
PubMed1994

[3H]-(+)-pentazocine binding to sigma recognition sites in human cerebellum.

The binding characteristics of the sigma-1 selective benzomorphan [3H]-(+)-pentazocine were determined in human cerebellar membranes. Saturation binding analysis revealed two affinity sites with a KDH of 1.4 +/- 0.7 nM and a KDL of 33.6 +/- 11.9 nM. Kinetic studies performed at 25 degrees C demonstrated reversible binding with association and dissociation rate constants determined for two classes of sites. In saturation binding studies, the addition of (+)-SKF 10,047 occluded binding of [3H]-(+)-pentazocine to high affinity sigma binding sites. The affinity profile of ligands displacing [3H]-(+)-pentazocine was consistent with the labeling of sigma-1 recognition sites with haloperidol > (+)-pentazocine > (+)-SKF 10,047 > (+)-3-PPP > DTG > (-)-pentazocine > (-)-SKF 10,047. The potency of the putative D3 receptor-selective ligand (+)-7-OH-DPAT was close to that measured for (+)-pentazocine in displacement experiments. These data suggest that [3H]-(+)-pentazocine labels sigma-1 sites in human cerebellum under appropriate assay conditions.

Binding Sites↗
PubMed1995

Differential alterations in muscarinic receptor subtypes in Alzheimer's disease: implications for cholinergic-based therapies.

Molecular subtypes of muscarinic receptors (m1-m5) are novel targets for cholinergic replacement therapies in Alzheimer's disease (AD). However, knowledge concerning the relative distribution, abundance and functional status of these receptors in human brain and AD is incomplete. Recent data from our laboratory have demonstrated a defect in the ability of the M1 receptor subtype to form a high affinity agonist-receptor-G protein complex in AD frontal cortex. This defect is manifested by decreased M1 receptor-stimulated GTPgammaS binding and GTPase activity and by a loss in receptor-stimulated phospholipase C activity. Normal levels of G proteins suggest that the aberrant receptor-G protein interaction may result from an altered form of the m1 receptor in AD. The combined use of radioligand binding and receptor-domain specific antibodies has permitted the re-examination of the status of muscarinic receptor subtypes in the human brain. In AD, normal levels of m1 receptor [3H]-pirenzepine binding contrasted with diminished m1 immunoreactivity, further suggesting that there is an altered form of the m1 receptor in the disease. Reduced m2 immunoreactivity was consistent with decreased numbers of m2 binding sites. Increased levels of m4 receptors were observed in both binding and immunoreactivity measurements. These findings suggest one possible explanation for the relative ineffectiveness of cholinergic replacement therapies used to date and suggest potential new directions for development of effective therapeutic strategies for AD.

Alzheimer Disease↗
PubMed1995

Identification of a primary metabolite of ibogaine that targets serotonin transporters and elevates serotonin.

Ibogaine is a hallucinogenic indole with putative efficacy for the treatment of cocaine, stimulant and opiate abuse. The purported efficacy of ibogaine following single dose administrations has led to the suggestion that a long-acting metabolite of ibogaine may explain in part how the drug reduces craving for psychostimulants and opiates. We report here that 12-hydroxyibogamine, a primary metabolite of ibogaine, displays high affinity for the 5-HT transporter and elevates extracellular 5-HT. In radioligand binding assays, 12-hydroxyibogamine was 50-fold more potent at displacing radioligand binding at the 5-HT transporter than at the DA transporter. Ibogaine and 12-hydroxyibogamine were equipotent at the dopamine transporter. In vivo microdialysis was used to evaluate the acute actions of ibogaine and 12-hydroxyibogamine on the levels of DA and 5-HT. Administration of 12-hydroxyibogamine produced a marked dose-related elevation of extracellular 5-HT. Ibogaine and 12-hydroxyibogamine failed to elevate DA levels in the nucleus accumbens over the dose range tested. The elevation in synaptic levels of 5-HT by 12-hydroxyibogamine may heighten mood and attenuate drug craving. The effects of the active metabolite on 5-HT transmission may account in part for the potential of ibogaine to interrupt drug-seeking behavior in humans.

Adult↗
PubMed1995

Interobserver agreement for measurement of grating acuity and interocular acuity differences with the teller acuity card procedure.

Interobserver reliability of the Teller acuity card (TAC) procedure for estimating acuity and interocular acuity differences (IADs) was assessed with 342 infants and children who had been treated in a neonatal intensive care unit for preterm birth and/or perinatal complications. Subjects were tested binocularly at term and monocularly at 4, 8, 11, 17, 24, 30, 36, and 48 months corrected age with TACs. Testers were masked to the location and spatial frequency of the grating on each card. Of the interobserver test-retest scores, 67% differed by no more than 0.5 octave, and 87% of the test pairs differed by no more than 1 octave. Of the test-retest comparisons of a subject's IAD, 54% showed agreement of 0.5 octave or better, and 76% differed by no more than 1 octave. Interobserver agreement for binocular and monocular tests was similar to that reported previously for visually and neurologically at-risk infants and children tested with the forced-choice preferential-looking procedure or with prototype acuity cards. Interobserver agreement for IAD estimates was somewhat less than that reported for a sample of infants with ocular disorders. There were no systematic differences in interobserver agreement between eyes tested first and eyes tested second, nor was interobserver agreement related to subject's medical diagnosis. Interobserver agreement was influenced, however, by the spatial frequencies of the particular gratings used during testing and, to a limited extent, by the age of the child. The duration of individual tests and observers' ratings of confidence in their acuity estimate were not reliable indicators of test-retest pairs that were not in agreement. The results demonstrate the reliability of the TAC procedure, but suggest that acuity estimates critical to a patient's diagnosis or treatment should be confirmed by repeat testing.

Age Factors↗
PubMed1991

Cocaethylene is more potent than cocaine in mediating lethality.

Cocaethylene is a pharmacologically active cocaine metabolite that is formed in the presence of ethanol by the activity of liver enzymes. The pharmacology of cocaethylene has not been extensively investigated and its acute toxicity is unknown. The acute toxicity of cocaethylene was compared to cocaine in Swiss-Webster mice. The LD50 of cocaethylene was 60.7 mg/kg and 63.8 mg/kg in female and male mice, respectively. In comparison, the LD50 of cocaine was 93.0 mg/kg in both female and male mice. These studies demonstrate that the cocaine-alcohol metabolite, cocathylene, is more potent in mediating lethality than the parent drug.

Animals↗
PubMed1992

Comparison of the concentration of messenger RNA encoding four muscarinic receptor subtypes in control and Alzheimer brains.

We determined the concentration of the messenger RNA species which encode four (m1-m4) of the five cloned muscarinic receptors in brains of Alzheimer's disease patients as compared to age-matched controls. Assays were performed using the quantitative method of DNA-excess solution hybridization in the cerebral cortex (frontal, temporal and occipital), hippocampus, nucleus basalis of Meynert and brainstem. The results suggest a statistically significant decrease in the m1 muscarinic receptor message in the temporal and occipital cortex, with no change in other regions. There was no change in the level of mRNA encoding the m2, m3 or m4 receptors in any of the brain regions studied.

Aged↗
PubMed1993

Handling characteristics of gallium alloy for dental restoration.

The handling characteristics of a gallium alloy (Gallium Alloy GF) were compared to those of a spherical high-copper amalgam (Tytin). Ten dentists each restored four identical MO preparations in acrylic typodont teeth (no. 30), two with amalgam and two with gallium alloy. Each restoration was evaluated immediately following completion by the operator for six clinically relevant criteria. Each criterion was scored between 1 and 5, where 1 = very poor, 2 = poor, 3 = fair, 4 = good, and 5 = very good. Three two-sided Mann-Whitney tests were used to compare the median scores for significant differences (P < 0.05). The first test indicated no significant difference between scores for the first- and second-placed restorations, within criteria and within alloy type (n = 10). The second test indicated a significant difference between amalgam and gallium alloy, within criteria and within restoration sequence (n = 10), for each criterion except resistance to fracture during removal of the matrix band. The third test indicated a significant difference between amalgam and gallium alloy, within each criteria, combining scores for first- and second-placed restorations (n = 20). During simulated clinical placement, amalgam was rated significantly higher than gallium alloy in each handling characteristic evaluated.

Dental Alloys↗
PubMed1986

Localization of nerve growth factor receptors in cholinergic neurons of the human basal forebrain.

Nerve growth factor (NGF) receptors were visualized in the basal human forebrain using an immunohistochemical procedure with a monoclonal antibody previously shown to recognize human melanoma cell NGF receptors. The receptors were found to be exclusively located in the medical septal nucleus, the diagonal band of Broca, and the nucleus basalis. This location coincided with that of cell bodies of ascending cholinergic neurons of the basal forebrain. In addition, NGF receptor-positive cells were costained for acetylcholinesterase. These findings indicate that cholinergic neurons of the basal forebrain but none of the other neurons located in this area express receptors for NGF. Results suggest that NGF acts as a trophic factor for cholinergic neurons in the human brain in a similar way as has been established in recent years for the rat brain.

Acetylcholinesterase↗
PubMed1995

Properties of ibogaine and its principal metabolite (12-hydroxyibogamine) at the MK-801 binding site of the NMDA receptor complex.

The putative anti-addiction alkaloid ibogaine and its principal metabolite 12-hydroxyibogamine appear to act at the (+)-5 methyl-10,11,dihydro-5H- dibenzo[a,d]cycloheten-5-10-imine maleate (MK-801) binding site in the N-methyl-D-aspartate (NMDA)-receptor cation channel. This conclusion is based on findings that both compounds competitively displaced specific [3H]MK-801 binding to membranes from postmortem human caudate and cerebellum and from frog spinal cord. Ibogaine was 4-6-fold more potent than its metabolite and both compounds were less potent (50-1000-fold) than MK-801 binding to the NMDA receptor. In addition, ibogaine (100 microM) and 12-hydroxyibogamine (1 mM) blocked (85-90% of control) the ability of NMDA (100 microM, 5 s) to depolarize frog motoneurons in the isolated frog spinal cord. The prevention of NMDA-depolarizations in frog motoneurons showed use-dependency and was very similar to the block produced by MK-801. In view of the abilities of MK-801 to affect the responses to addictive substances in pre-clinical investigations, our results are compatible with the idea that the ability of ibogaine and 12-hydroxyibogamine to interrupt drug-seeking behavior may, in part, result from their actions at the MK-801 binding site.

Adult↗
PubMed1986

Autoradiographic localization of M1 and M2 muscarine receptors in the rat brain.

The distribution of M1 and M2 muscarine receptors in the rat brain was investigated by in vitro autoradiography. Muscarine receptors were visualized after complete receptor uncoupling in ethylenediaminetetraacetic acid buffer containing 1 mM N-ethyl maleimide and saturation with the ligand [3H]quinuclidinyl benzilate. Pirenzepine, an M1-selective antagonist, was used in our assays as a counter ligand to occlude M1 sites, allowing the primary ligand, [3H]quinuclidinyl benzilate, to label the remaining M2 muscarine receptors. In adjacent section, M1 muscarine receptors were labelled with [3H]quinuclidinyl benzilate in the presence of sufficient carbachol, and M2-selective agonist, to inhibit the binding to M2 sites. Our results reveal a heterogeneous distribution of M1 and M2 receptors. Increased densities of carbachol-resistant and pirenzepine-sensitive sites (M1 receptor subtype) were apparent over many forebrain structures including the olfactory tubercle, caudate-putamen, nucleus accumbens, hippocampus, amygdala and cerebral cortex. In contrast, pirenzepine-resistant and carbachol-sensitive sites (M2 receptor subtype) were distributed throughout the brain with increased densities apparent over regions known to contain large numbers of cholinergic cell bodies. M2 receptor localization patterns were largely coincident with the regional distribution and intensity of acetylcholinesterase positive sites. Since the M2 receptor pattern appears to parallel regional innervation densities, we conclude that the M2 receptor may serve as a marker for cholinergic pathways. The findings also suggest that M1 muscarine receptors are involved in the presumptive postsynaptic actions of acetylcholine in many forebrain structures.

Acetylcholine↗
PubMed2026

Acyloxyacyl Hydrolase-Mediated Lipopolysaccharide Inactivation Limits Macrophage Endotoxin Tolerance and Promotes Inflammation and Fibrosis in Metabolic Dysfunction-Associated Steatohepatitis.

BACKGROUND & AIMS: Metabolic dysfunction-associated steatohepatitis, a chronic liver disease, is characterized by persistent low-grade inflammation, partially driven by gut-derived lipopolysaccharide. Although repeated lipopolysaccharide exposure can induce endotoxin tolerance in innate immune cells, its role in chronic liver diseases remains unclear. Acyloxyacyl hydrolase is an endogenous enzyme that inactivates lipopolysaccharide, potentially modulating this process. We aimed to investigate how acyloxyacyl hydrolase regulates endotoxin tolerance in Kupffer cells and how this affects hepatic inflammation and fibrosis during metabolic dysfunction-associated steatohepatitis progression. METHODS: Acyloxyacyl hydrolase-deficient mice and wild-type controls were subjected to multiple dietary metabolic dysfunction-associated steatohepatitis models. Inflammatory responses, fibrosis, and transcriptomic changes in liver tissues and isolated Kupffer cells were analyzed. Endotoxin tolerance was modulated through &#x3b2;-glucan administration or lipopolysaccharide preconditioning. Lipopolysaccharide bioactivity was assessed using Toll-like receptor 4-reporter cell assays. RESULTS: Lipopolysaccharide-preconditioned Kupffer cells exhibited reduced proinflammatory cytokine production and transcriptional suppression of inflammatory pathways, indicating tolerance. Despite slight elevation of plasma lipopolysaccharide levels in metabolic dysfunction-associated steatohepatitis, upregulation of hepatic acyloxyacyl hydrolase positively correlated with disease severity, suggesting enhanced lipopolysaccharide inactivation but impaired establishment of tolerance. In contrast, acyloxyacyl hydrolase-deficient Kupffer cells displayed reinforced endotoxin tolerance, leading to diminished hepatic inflammation and fibrosis. Reversal of tolerance using &#x3b2;-glucan reactivated inflammatory and fibrogenic responses in acyloxyacyl hydrolase-deficient mice, whereas tolerance induction by low-dose lipopolysaccharide preconditioning mitigated metabolic dysfunction-associated steatohepatitis pathology, supporting the protective role of macrophage tolerance in chronic liver injury. CONCLUSIONS: Endotoxin tolerance in Kupffer cells represents a protective mechanism against chronic liver inflammation and fibrosis. Acyloxyacyl hydrolase regulates this state by limiting bioactive lipopolysaccharide, thereby modulating the establishment of endotoxin tolerance and downstream inflammatory and fibrotic responses. Enhancing macrophage tolerance by utilizing lipopolysaccharide may offer a novel therapeutic avenue to control the progression of metabolic dysfunction-associated steatohepatitis.

AOAH↗
PubMed2006

Multidimensional shape similarity in the development of visual object classification.

The current work examined age differences in the classification of novel object images that vary in continuous dimensions of structural shape. The structural dimensions employed are two that share a privileged status in the visual analysis and representation of objects: the shape of discrete prominent parts and the attachment positions of those parts. Experiment 1 involved a triad classification task in which participants at each of three different ages (5 years, 8 years, and adult) classified object images from two distinct stimulus sets. Across both sets, the youngest children demonstrated a systematic bias toward the shape of discrete parts during their judgments. With increasing age, participants increasingly came to select both the shape and the position of parts when classifying the images. The findings from Experiment 2 indicate that the local shape bias observed in young children's classifications is not merely a consequence of a discrimination advantage for that dimension. Results are discussed in relation to corresponding age-related changes in other functional contexts of visual processing.

Adult↗
PubMed2005

Norepinephrine transporter immunoblotting and radioligand binding in cocaine abusers.

The norepinephrine transporter (NET) is a membrane protein responsible for transporting extracellular norepinephrine. The cocaine and tricyclic antidepressant-sensitive NET belongs to a family of sodium and chloride coupled transporters that include the monoamines dopamine and serotonin and the amino acids GABA and glycine. The regional distribution of the NET has been defined by synaptosomal uptake of norepinephrine and by autoradiographic approaches in rodent and primate brain. However, the NET has not been well characterized in the human brain due to the overall low abundance of protein expressed in axon terminals. Recently, immunolocalization studies have been used to identify the regional distribution of the cytoplasmic NET epitope in rodent brain. We report here on the characteristics of drug interactions with the native NET protein in human postmortem brain. Antisera raised against a 17-amino acid peptide from the N-terminus of the hNET recognized an 80 kDa species in human cerebral cortex. Chronic exposure to cocaine upregulated NET protein expression and [3H]nisoxetine binding sites in the insular cortex from brains of cocaine addicts. These results demonstrate that immunologic and radioligand binding approaches afford specific labeling of the native transport protein in postmortem human brain.

Antibodies↗
PubMed2007

Phenotypic associations of tau and ApoE in Parkinson's disease.

Overlaps in clinical, pathological and molecular features of Parkinson's disease (PD), dementing and motor tauopathies have prompted association studies in search of common genetic risk factors that may predispose or modify this spectrum of disorders. To explore possible phenotypic implications, we studied common tau and ApoE gene polymorphisms, associated with Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and PD, in a clinically and pathologically characterized cohort of PD patients and aged control subjects. Our results reveal a novel association between PD-related hallucinations and H1H1 genotype. We also report an association between PDD and the presence of the ApoE epsilon4 allele. Better determination of subsets of PD patients based upon the presence of specific phenotypic features may improve the accuracy of association studies.

Aged↗
PubMed2005

Spatial memory in aged rats is related to PKCgamma-dependent G-protein coupling of the M1 receptor.

In the present study, individual differences in spatial memory in aged Fischer 344 (F344) rats were associated with the extent of G-protein coupling of the M1 muscarinic receptor and the dendritic-to-somal ratio of hippocampal PKCgamma (d/sPKCgamma) immunogenicity. Following testing in the eight-arm radial maze task, 7 young and 13 aged rat brains were sectioned through the dorsal hippocampal formation (HF). G-protein coupling of the M1 receptor was assessed autoradiographically using competition binding studies in the presence and absence of a G-protein uncoupler to determine high (K(H)) and low (K(L)) affinity states for agonist in the HF, neocortex, and amygdala. In aged animals, a relationship between choice accuracy in the maze and K(H), a measure of M1 receptor-G-protein coupling was seen in the dentate gyrus, CA3, CA1, and neocortex. Furthermore, choice accuracy and d/sPKCgamma immunogenicity showed a significant relationship in CA1. Lastly, a correlation was seen in the CA1 of aged animals between K(H) and d/sPKCgamma. These relationships did not hold for the amygdala. Thus, individual differences in a naturally occurring age-dependent disruption of cholinergic-PKCgamma signal transduction is associated with spatial memory dysfunction.

Age Factors↗
PubMed2006

Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease.

Neurofibrillary degeneration in the nucleus basalis and a loss of its cortical cholinergic projections are prominent components of the neuropathology in Alzheimer's disease (AD). The AD brain is also associated with a degeneration of the noradrenergic projections arising from the nucleus locus coeruleus (LC), but the time course of this lesion is poorly understood. To determine whether the LC displays neurofibrillary abnormalities early in the course of events leading to AD, we examined tissue specimens from seven cognitively normal controls and five subjects at the stages of mild cognitively impairment (MCI) or early AD. Tyrosine hydroxylase immunochemistry was used as a marker of LC neurons while AT8 immunolabeling visualized abnormal tau associated with neurofibrillary tangles and their precursors. Thioflavine-S was used as a marker for fully developed tangles. We found that AT8-positive labeling and thioflavine-S positive tangles were present in both groups of specimens. However, the percentage of neurons containing each of these markers was significantly higher in the cognitively impaired group. The MMSE scores displayed a negative correlation with both markers of cytopathology. These results indicate that cytopathology in the LC is an early event in the age-MCI-AD continuum and that it may be listed among the numerous factors that mediate the emergence of the cognitive changes leading to dementia.

Acetylcholinesterase↗