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Biomedical subjects

V Stone

Publications and source records attributed to V Stone.

At least 37 records · Page 2Linked to original sources
PubMed1999

Recognition of faux pas by normally developing children and children with Asperger syndrome or high-functioning autism.

Most theory of mind (ToM) tests are designed for subjects with a mental age of 4-6 years. There are very few ToM tests for subjects who are older or more able than this. We report a new test of ToM, designed for children 7-11 years old. The task involves recognizing faux pas. Study 1 tested 7-9, and 11-year-old normal children. Results showed that the ability to detect faux pas developed with age and that there was a differential developmental profile between the two sexes (female superiority). Study 2 tested children with Asperger syndrome (AS) or high-functioning autism (HFA), selected for being able to pass traditional 4- to 6-year level (first- and second-order) false belief tests. Results showed that whereas normal 9- to 11-year-old children were skilled at detecting faux pas, children with AS or HFA were impaired on this task. Study 3 reports a refinement in the test, employing control stimuli. This replicated the results from Study 2. Some patients with AS or HFA were able to recognize faux pas but still produced them. Future research should assess faux pas production.

Asperger Syndrome↗
PubMed1998

Vasopressin-induced disruption of actin cytoskeletal organization and canalicular function in isolated rat hepatocyte couplets: possible involvement of protein kinase C.

The effect of vasopressin (VP) on canalicular function and hepatocellular morphology, with particular regard to actin cytoskeletal organization and the concomitant plasma membrane bleb formation, was studied in isolated rat hepatocyte couplets. VP induced the concentration-dependent formation of multiple plasma membrane blebs as well as simultaneous impairment in both canalicular vacuolar accumulation (cVA) and retention (cVR) of the fluorescent bile acid, cholyl-lysyl-fluorescein (CLF), which evaluate couplet secretory function and tight-junction integrity, respectively. These effects were mimicked by the protein kinase C (PKC) activator, phorbol dibutyrate (PDB), but not by the protein kinase A (PKA) activator, dibutyryl-cAMP. VP-induced bleb formation and canalicular dysfunction were fully prevented by the protein kinase inhibitor, H-7, but not by the PKA inhibitor, KT5720, further suggesting a specific role of PKC. VP-induced alterations were also prevented by pretreatment with the Ca2+-buffering agent, BAPTA/AM, but not with the calmodulin-dependent protein kinase II antagonist, calmidazolium. Neither the Ca2+-activated neutral protease inhibitor, leupeptin, nor the antioxidants, alpha-tocopherol or deferoxamine, were able to prevent either VP-induced plasma membrane blebbing or canalicular dysfunction. The Ca2+-ionophore, A23187, mimicked the VP-induced alterations, but its harmful effects were completely prevented by H-7. Bleb formation induced by VP and PDB was accompanied by an extensive redistribution of filamentous actin from the pericanalicular area to the cell body, and this effect was fully prevented by H-7. These results suggest that VP-induced canalicular and cytoskeletal dysfunction is mediated by PKC and that classical (Ca2+-dependent) PKC appear to be involved because intracellular Ca2+ is required for VP to induce its harmful effects.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1998

Absence of linkage between inflammatory bowel disease and selected loci on chromosomes 3, 7, 12, and 16.

BACKGROUND & AIMS: Linkage data derived from genome-wide scans of inflammatory bowel disease (IBD) sibling-pair families have identified 4 loci on chromosomes 3, 7, 12, and 16 as potential sites for IBD susceptibility genes. The aim of this study was to investigate whether linkage analysis of another independently collected set of sibling pairs with IBD would provide further evidence of linkage between these previously reported loci and IBD. METHODS: Using the MAPMAKER/SIBS program, the segregation of 21 microsatellite marker loci spanning the 4 putative IBD gene loci was analyzed in a study population comprising 161 families with 114 Crohn's disease, 36 ulcerative colitis, and 50 mixed IBD sibling pairs from the Greater Toronto area. RESULTS: The results of multipoint linkage analysis showed no evidence for linkage between IBD and each of the 21 marker loci studied; the logarithm of odds scores in all instances were less than 0.8. These linkage data were found, by exclusion mapping analysis, to exclude values of lambdas ranging from 1.5 to 3.0, depending on the locus evaluated. CONCLUSIONS: The loci previously suggested as representing IBD susceptibility loci are not linked to IBD in the Toronto population examined in this analysis.

Chromosome Mapping↗
PubMed1996

Comparison of the effects of redox cycling and arylating quinones on hepatobiliary function and glutathione homeostasis in rat hepatocyte couplets.

Menadione (2-methyl-1,4-naphthoquinone, a redox cycling and arylating quinone; 5-100 microM) inhibited the canalicular vacuolar accumulation (CVA) of a fluorescent bile acid, cholyl-lysyl-fluorescein (CLF), in rat hepatocyte couplets. This was associated with depletion of reduced glutathione and accumulation of oxidized glutathione, the latter indicating that the concentrations of menadione used were able to induce oxidative stress. There was no associated cytotoxicity as indicated by ATP content. Treatment of couplets with the redox cycling quinone 2,3-dimethoxy-1,4-naphthoquinone (up to 100 microM) had relatively little effect on CVA, suggesting that the magnitude of reactive oxygen formation induced by this compound was insufficient to disrupt canalicular integrity. In comparison, the arylation of protein thiol groups by p-benzoquinone (up to 100 microM) proved to be more potent in inhibiting canalicular vacuolar accumulation. The predominant mechanism of menadione-induced inhibition of couplet hepatobiliary function is therefore more likely to involve the arylation of critical thiol groups (such as those in the F-actin cytoskeleton) rather than their oxidation. The oxidative effects of menadione could, however, potentiate the deleterious effects induced by arylation, such as by reduced glutathione depletion.

Adenosine Triphosphate↗
PubMed1996

Relationship of sexual mixing across age and ethnic groups to herpes simplex virus-2 among unmarried heterosexual adults with multiple sexual partners.

Sexual mixing is important to understanding how sexually transmitted diseases (STDs) spread in the general population, and, identifying people who mix across social groups aids HIV-STD prevention. The authors examined (a) the extent to which people have sexual partners from other sexual networks (disassortative mixing) in a probability sample of unmarried heterosexual adults reporting multiple sexual partners (N = 545) and (b) the relationship between mixing and Herpes Simplex Virus-2 (HSV-2). After demographic variables and number of lifetime sexual partners were controlled for, heavy mixers were significantly more likely to be HSV-2 positive. Degree of mixing down produced the most powerful relationship to HSV-2. Age, education, ethnicity, and a history of incarceration or IV drug use were found to distinguish between light and heavy mixers, although differences between ethnic and age mixing were observed. The results have implications for understanding HIV-STD transmission and for directing interventions toward population segments at high risk for transmitting HIV-STDs.

Adult↗
PubMed1995

Hepatobiliary function and toxicity in vitro using isolated hepatocyte couplets.

1. Hepatocyte couplets can be routinely prepared from rat liver to produce a suitable in vitro model for polarized primary cells. 2. Centrifugal elutriation provides a means of producing enriched subpopulations of periportal and perivenous couplets from the same liver, thus providing a means of studying the influence of zonal heterogeneity on hepatobiliary function. 3. The maintenance of structural and secretory polarity demonstrated by hepatocyte couplets provides a convenient in vitro system for mechanistic studies of factors both regulatory and adversely affecting hepatobiliary functions. 4. Couplets are also uniquely appropriate for specific studies of regulation at the biliary pole, on the performance of junctions and on the maintenance and rate of transcytotic movement. 5. The possibility also exists that effects of an in vivo pre-exposure to agents causing hepatobiliary dysfunction can be assessed in couplets ex vivo.

Animals↗
PubMed1994

Effect of oxidative stress and disruption of Ca2+ homeostasis on hepatocyte canalicular function in vitro.

Isolated rat hepatocyte couplets were used to study the effects of menadione and a rise in the intracellular concentration of calcium on biliary canalicular function. Canalicular function was assessed by counting the percentage of couplets which were able to accumulate the fluorescent cholephile, cholyl lysyl fluorescein (CLF) into the canalicular vacuole between the two cells. Menadione induced a concentration-dependent inhibition of the canalicular vacuole accumulation (CVA) of CLF reaching 7.6 +/- 1.8% of control at 100 microM menadione. This disruption was not prevented by blocking receptor-operated calcium channels with Ni2+ (300 microM). The concentration range of menadione used did not deplete cellular ATP content. In contrast glutathione content was reduced to 52% of its control value by 100 microM menadione. A rise in cytosolic calcium induced by the calcium ionophore, A23187 (up to 30 microM) also disrupted CVA in a concentration-dependent manner. Release of endoplasmic reticulum calcium stores by thapsigargin (50 nM) affected the retention of canalicular contents to a much lesser extent, although it was able to stimulate a reduction in canalicular area to 40% of its original value, assumed to be due to canalicular contraction. Menadione (30 and 100 microM) reduced the fluorescence of phalloidin-FITC-labelled F-actin in both the total and pericanalicular cytoskeleton. Canalicular function was therefore disrupted by non-lethal concentrations of menadione via a mechanism which does not appear to involve ATP depletion or the entry of extracellular calcium, but is associated with a depletion of both cellular glutathione and F-actin. An increase in the concentration of intracellular calcium can stimulate canalicular contraction, and at relatively high concentrations calcium can also disrupt canalicular function.

Actins↗
PubMed1992

Extrapolation of linear motion.

We investigated observers' ability to extrapolate a linear trajectory of a moving point, in order to determine how effectively the visual system can combine orientation and position information for moving stimuli. Observers saw a probe dot moving along a straight line toward a stationary target dot. The probe dot extinguished before reaching the target, and the observers' task was to judge whether an extrapolation of the trajectory of the probe would pass to the left or right of the target. Performance was measured as a function of probe velocity, length of the visible trajectory, and location of the target. The empirical results indicated that over a range of conditions, performance on this task is qualitatively similar to, but somewhat less accurate than, that on an analogous task with static stimuli. A four-component model is presented to account for the results. The model specifies an accurate extraction of probe motion parameters, extrapolation of the motion by an ideal observer, and limitations on the input to these processes in the form of visual field spatial inhomogeneity and temporal decay of position information.

Depth Perception↗
PubMed1986

Practice nurses and antismoking education.

A questionnaire on antismoking activities and education was sent to 369 nurses in general practice. The response rate was 80%. Although most of the nurses sometimes advised patients about smoking, routine antismoking education occurred less frequently. Only a few regularly referred smokers to other agencies for help, recommended aids to stop smoking, or used antismoking literature. Although the nurses thought that they had an important role in helping smokers to give up, they expressed little confidence in their effectiveness, believing that advice from the general practitioner and the smoker's personal determination to give up have more impact. The nurses expressed a need for training in antismoking education. Seventy seven per cent were interested in attending seminars and listed information about smoking, techniques for stopping, and counselling skills as priorities. If practice nurses are to use opportunities in primary care to help smokers there is clearly a need to provide further training and to establish the effectiveness of nurses in their role as smoking educators.

Attitude of Health Personnel↗