Anomalous calcium secretion in rat ileum: role of paracellular pathway.

The mechanism of apparent calcium secretion by unstripped rat ileum in vitro has been investigated using mannitol and polyethylene glycol (mol wt 900) as markers for extracellular transepithelial flux. In the absence of electrochemical gradients between the mucosal and serosal bathing media in a modified Ussing chamber, net fluxes of both mannitol and polyethylene glycol were observed from serosa to mucosa in the presence of 11 mM D-glucose. Mucosal-to-serosal calcium flux reveals a significant cellular component, but serosal-to-mucosal calcium permeability is a linear function of mannitol permeability, suggesting an exclusively extracellular route. For the mucosal-to-serosal fluxes, inhibition of calcium flux by 1 mM N-ethylmaleimide results in a calcium-to-mannitol permeability ratio indistinguishable from that measured for serosal-to-mucosal flux. This evidence suggests that the apparent calcium secretion observed at 10 mM medium calcium is not the result of a cellular secretory mechanism. It is proposed that a hydrostatic driving force generated internal to the tissue but external to the cells results in net calcium secretion at calcium conentrations that saturate the cellular absorptive mechanism.     

Modulation of amygdalar activity by the conscious regulation of negative emotion

Lesion and neuroimaging studies suggest the amygdala is important in the perception and production of negative emotion; however, the effects of emotion regulation on the amygdalar response to negative stimuli remain unknown. Using event-related fMRI, we tested the hypothesis that voluntary modulation of negative emotion is associated with changes in neural activity within the amygdala. Negative and neutral pictures were presented with instructions to either "maintain" the emotional response or "passively view" the picture without regulating the emotion. Each picture presentation was followed by a delay, after which subjects indicated how they currently felt via a response keypad. Consistent with previous reports, greater signal change was observed in the amygdala during the presentation of negative compared to neutral pictures. No significant effect of instruction was found during the picture presentation component of the trial. However, a prolonged increase in signal change was observed in the amygdala when subjects maintained the negative emotional response during the delay following negative picture offset. This increase in amygdalar signal due to the active maintenance of negative emotion was significantly correlated with subjects' self-reported dispositional levels of negative affect. These results suggest that consciously evoked cognitive mechanisms that alter the emotional response of the subject operate, at least in part, by altering the degree of neural activity within the amygdala.     

Distinctions between manipulation and function knowledge of objects: evidence from functional magnetic resonance imaging

A prominent account of conceptual knowledge proposes that information is distributed over visual, tactile, auditory, motor and verbal-declarative attribute domains to the degree to which these features were activated when the knowledge was acquired [D.A. Allport, Distributed memory, modular subsystems and dysphagia, In: S.K. Newman, R. Epstein (Eds.), Current perspectives in dysphagia, Churchill Livingstone, Edinburgh, 1985, pp. 32-60]. A corollary is that when drawing upon this knowledge (e.g., to answer questions), particular aspects of this distributed information is re-activated as a function of the requirements of the task at hand [L.J. Buxbaum, E.M. Saffran, Knowledge of object manipulation and object function: dissociations in apraxic and non-apraxic subjects. Brain and Language, 82 (2002) 179-199; L.J. Buxbaum, T. Veramonti, M.F. Schwartz, Function and manipulation tool knowledge in apraxia: knowing 'what for' but not 'how', Neurocase, 6 (2000) 83-97; W. Simmons, L. Barsalou, The similarity-in-topography principle: Reconciling theories of conceptual deficits, Cognitive Neuropsychology, 20 (2003) 451-486]. This account predicts that answering questions about object manipulation should activate brain regions previously identified as components of the distributed sensory-motor system involved in object use, whereas answering questions about object function (that is, the purpose that it serves) should activate regions identified as components of the systems supporting verbal-declarative features. These predictions were tested in a functional magnetic resonance imaging (fMRI) study in which 15 participants viewed picture or word pairs denoting manipulable objects and determined whether the objects are manipulated similarly (M condition) or serve the same function (F condition). Significantly greater and more extensive activations in the left inferior parietal lobe bordering the intraparietal sulcus were seen in the M condition with pictures and, to a lesser degree, words. These findings are consistent with the known role of this region in skilled object use [K.M. Heilman, L.J. Gonzalez Rothi, Apraxia, In: K.M. Heilman, E. Valenstein (Eds.), Clinical Neuropsychology, Oxford University Press, New York, 1993, pp. 141-150] as well as previous fMRI results [M. Kellenbach, M. Brett, K. Patterson, Actions speak louder than functions: the importance of manipulability and action in tool representation, Journal of Cognitive Neuroscience, 15 (2003) 30-46] and behavioral findings in brain-lesion patients [L.J. Buxbaum, E.M. Saffran, Knowledge of object manipulation and object function: dissociations in apraxic and non-apraxic subjects, Brain and Language, 82 (2002) 179-199]. No brain regions were significantly more activated in the F than M condition. These data suggest that brain regions specialized for sensory-motor function are a critical component of distributed representations of manipulable objects.     

Power in Voxel-based lesion-symptom mapping

Lesion analysis in brain-injured populations complements what can be learned from functional neuroimaging. Voxel-based approaches to mapping lesion-behavior correlations in brain-injured populations are increasingly popular, and have the potential to leverage image analysis methods drawn from functional magnetic resonance imaging. However, power is a major concern for these studies, and is likely to vary regionally due to the distribution of lesion locations. Here, we outline general considerations for voxel-based methods, characterize the use of a nonparametric permutation test adapted from functional neuroimaging, and present methods for regional power analysis in lesion studies.     

Effect of cortisone treatment on the active transport of calcium by the small intestine

It is generally recognized that glucocorticoid administration may diminish calcium absorption in vivo as well as the active transport of calcium by the intestine in vitro. Recent studies by others have emphasized the possibility of an alteration in the metabolism of vitamin D to 25-hydroxycholecalciferol in accounting for the steroid effects on calcium absorption. The results obtained in the present studies fail to support this hypothesis.The present studies confirm that the administration of cortisone or other glucocorticoids to the rat interferes with the active transport of calcium by duodenal gut sacs in vitro. This abnormality is not due to an alteration in the permeability of the intestine to calcium, and it cannot be corrected by the administration of either massive doses of vitamin D(2) or modest doses of 25-hydroxycholecalciferol. Experiments concerned with the effects of cortisone on the level of the vitamin D-dependent duodenal calcium-binding protein, the amount of bioassayable vitamin D activity in the mucosa, and the distribution and metabolism of (3)H-vitamin D(3), did not provide evidence in favor of a harmone-related defect in either the localization of vitamin D or its metabolism to 25-hydroxycholecalciferol. Alterations in the transport of iron and D-galactose, not dependent on vitamin D, suggest that cortisone treatment may be responsible for more than a simple antagonism to the effects of vitamin D.The results of the present studies indicate that cortisone administration affects the cellular mechanisms mediating calcium transport in a manner that is opposite to the effects of vitamin D, but seems to be independent of any direct interaction with the parent vitamin or its metabolites. If a disorder in vitamin D metabolism is at all involved, it is at a step subsequent to 25-hydroxylation.