Neural basis for verb processing in Alzheimer's disease: an fMRI study

Patients with probable Alzheimer's disease (AD) have difficulty understanding verbs. To investigate the neural basis for this deficit, the authors used functional magnetic resonance imaging to examine patterns of neural activation during verb processing in 11 AD patients compared with 16 healthy seniors. Subjects judged the pleasantness of verbs, including MOTION verbs and COGNITION verbs. Healthy seniors and AD patients both activated posterolateral temporal and inferior frontal regions during judgments of verbs. These activations were relatively reduced and somewhat changed in their anatomic distribution in AD patients compared with healthy seniors, particularly for the subcategory of MOTION verbs, but AD patients showed minimal activation in association with COGNITION verbs. These findings imply that poor performance with verbs in AD is due in part to altered activation of the large-scale neural network that supports verb processing.     

The output of the hippocampus is inhibited during social behavior in the male rat

We tested the role of C5 segment inspiratory interneurons in transcribing central respiratory drive to phrenic motoneurons and mediating intersegmental reflexes by cross-correlating the spontaneous activity of 26 interneurons with that of the ipsi -and contralateral C5 phrenic nerves in decerebrate cats. There were 10 interneurons that discharged only during inspiration (phrenic burst) and 16 that discharged tonically with increased firing during inspiration. Of the cross-correlograms for 26 of the interneurons with the ipsilateral phrenic, 20 were flat and 2 had peaks centred about time zero, interpreted as a common activation of the interneurons and motoneurons. The cross-correlograms for 4 other interneurons had troughs centred about time zero, interpreted as a synchronous excitation of the interneurons and inhibition of the motoneurons. Of the cross-correlograms for 23 interneurons with the contralateral phrenic, 22 were flat and 1 had a peak centred about time zero, interpreted as a common activation of the interneuron and motoneurons. Nine of ten cross-correlograms between pairs of interneurons were flat; one had a peak centred about time zero. We conclude that, despite their inspiratory modulated discharge patterns, there is no evidence from this study that the C5 segment inspiratory interneurons convey central respiratory drive to C5 phrenic motoneurons.     

Lack of complete correlation between emetic and T-cell-stimulatory activities of staphylococcal enterotoxins.

This study examined the emetic activity of several staphylococcal enterotoxin type A and B (SEA and SEB, respectively) mutants that had either one or two amino acid residue substitutions. New sea gene mutations were constructed by site-directed mutagenesis; gene products were obtained with glycine residues at position 25, 47, 48, 81, 85, or 86 of mature SEA. Culture supernatants from Staphylococcus aureus RN4220, or derivatives containing either sea or a sea mutation, were analyzed for the ability to stimulate proliferation of murine splenocytes, as determined by incorporation of [3H]thymidine. Culture supernatants containing SEA-N25G (a SEA mutant with a substitution of glycine for the asparagine residue at position 25), SEA-F47G, or SEA-L48G did not stimulate T-cell proliferation, unlike supernatants containing the other substitution mutants. Purified preparations of SEA-N25G had weak activity and those of SEA-F47G and SEA-L48G had essentially no activity in the T-cell proliferation assay. All mutants except SEA-V85G, which was degraded by monkey stomach lavage fluid in vitro, were tested for emetic activity. SEA-C106A and two SEB mutants, SEB-D9N/N23D and SEB-F44S (previously referred to as BR-257 and BR-358, respectively), whose construction and altered immunological properties have been reported previously, were also tested in the emetic assay. Each mutant was initially administered intragastrically at doses of 75 to 100 micrograms per animal; if none of the animals responded, the dose was increased four-to fivefold. SEA-F47G, SEA-C106A, and SEB-D9N/N23D were the only mutants that did not induce vomiting at either dose tested; these three mutants had reduced immunological activity. However, there was not a perfect correlation between immunological and emetic activities; SEA-L48G and SEB-F44S retained emetic activity, although they had essentially no T-cell-stimulatory activity. These studies suggest that these two activities can be dissociated.     

Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea

We measured pharyngeal cross-sectional area and its change with alterations in lung volume in 10 subjects who snored and had obstructive sleep apnea, 6 subjects who snored and did not have obstructive sleep apnea, and 9 subjects who did not snore. Pharyngeal area was measured with use of an acoustic-reflection technique. We found that snorers with and without sleep apnea had a significantly smaller mean (+/- SE) pharyngeal cross-sectional area (4.1 +/- 0.2 and 3.7 +/- 0.9 cm2, respectively) at functional residual capacity than nonsnorers (5.4 +/- 0.5 cm2, P less than 0.025). When lung volume decreased from functional residual capacity to residual volume, both nonsnorers and snorers with sleep apnea had a decrease in pharyngeal area (from 5.4 +/- 0.5 to 4.5 +/- 0.4 cm2 and 4.1 +/- 0.2 to 3.4 +/- 0.2 cm2, respectively), whereas snorers without sleep apnea had no such decrease, suggesting that their pharynxes were less collapsible at low lung volumes. We conclude that snorers with and without sleep apnea have smaller pharyngeal cross-sectional areas than nonsnorers and that snorers with sleep apnea have a further decrease as lung volume falls.     

Studies on the cytosolic estrogen receptor from rat thymus

The estrogen receptor present in rat thymus cytosol was characterized by its association constant, KA, the number of binding sites present, Bmax, and by the effect of added estradiol on the binding parameters. The binding parameters were determined by fitting the raw binding data directly to the hyperbolic binding function, and the Lineweaver-Burk, Scatchard, and Woolf linear transforms of the hyperbolic function. The binding parameters were also determined using the direct linear plot method of Eisenthal and Cornish-Bowden. The Woolf plot and the direct linear plot gave results that indicated that added estradiol caused both competitive and noncompetitive inhibition of the receptor. The Scatchard and Lineweaver-Burk methods were not capable of showing a systematic trend. The parameters derived from the hyperbolic binding equation were in agreement with the Woolf and direct linear plot methods. The results of this study show that the cytosolic estrogen receptor from rat thymus is both competitively and noncompetitive inhibited by estradiol.     

Volume and surface area estimates of astrocytes in the sensorimotor cortex of the cat

Electron micrographs of random sections through 133 astrocytes taken from the anterior and posterior sigmoid gyri of adult cats were used to estimate average astrocyte cell volume. Average soma volume was derived by two methods: (1) assuming that each approximated the shape of a prolate spheroid, a value of 2.2 ± 0.1 × 10^?13l. was calculated by substituting measurements of major (mean 10.4 ± 0.2 μm) and minor (mean 6.2 ± 0.1 μm) cell axes into the formula for volume; (2) applying Weibel's point-counting method of morphometry, a value of 1.9 ± 0.09 × 10^?13l. was obtained based on ratios of volume density and nuclear volume, calculated from measurements of nuclear axes. Because of the use of random sections through the cells sampled, the axial measurements on which both methods depend represent possible underestimations by as much as 21%; the resulting average value for soma volume might be as much as 3.2 × 10^?13l. Astrocyte somata from the deepest layer of the cortex had a significantly larger average volume than those from more superficial layers (P < 0.05). Average total cell volume (soma plus processes), estimated by calculating the volume of the tissue sample that was occupied by astrocytes and dividing that value by the number of astrocytes in the sample, amounted to 5.7 × 10^?13l. Point-counting morphometry revealed that 15.5% of the cortex consists of astrocytic cytoplasm. Average total cell surface area, estimated from intercepts of grid lines with cell membrane profiles of astrocytes within the sample, was 1.9 × 10^?5 cm²; average surface area of astrocyte somata, based on axial measurements, amounted to 2.5 × 10^?6 cm² or 13% of the surface area of the whole cell.Only 18 gap junctions were identified in the random sections through 133 astrocytes; these and other considerations bearing on the possible relationship of the data presented to electrical measurements in living astrocytes are discussed.     

Effect of atropine and vagotomy on response of transplanted pancreas.

It is well established that atropine and vagotomy inhibit pancreatic enzyme secretion in response to intestinal stimulants such as fat or amino acids. These effects are usually attributed to interference with hypothetical vagal cholinergic mechanisms that facilitate release of cholecystokinin. To determine whether atropine or vagotomy interferes with release of humoral stimulants of pancreatic enzyme secretion, we studied their effect on protein secretion from an autotransplanted portion of pancreas in response to intestinal stimulants in dogs. The transplanted pancreas was as sensitive as the intact pancreas to stimulation by exogenous caerulein, a cholecystokinin-like peptide, and this response was not altered by atropine or vagotomy. Therefore, if vagotomy or atropine interferes with release of humoral pancreatic stimulants, they would be expected to reduce the response of the transplanted pancreas just as they do of the intact pancreas. Truncal vagotomy caused no significant change in protein secretion from the transplant in response to intestinal perfusion with sodium oleate or tryptophan. Atropine was tested only against sodium oleate and caused no change in response. We conclude that release of humoral pancreatic excitants of protein secretion in response to intestinal stimulants is not significantly changed by atropine or vagotomy.