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PubMed2002

Word length and orthographic neighborhood size effects in the left and right cerebral hemispheres.

Previous studies have reported an interaction between visual field (VF) and word length such that word recognition is affected more by length in the left VF (LVF) than in the right VF (RVF). A reanalysis showed that the previously reported effects of length were confounded with orthographic neighborhood size (N). In three experiments we manipulated length and N in lateralized lexical decision tasks. Results showed that length and VF interacted even with N controlled (Experiment 1); that N affected responses to words in the LVF but not the RVF (Experiment 2); and that when length and N were combined, length only affected performance in the LVF for words with few neighbors.

Adolescent↗
PubMed2002

Libet's temporal anomalies: a reassessment of the data.

Benjamin Libet compared the perceived time of direct brain stimulation to the perceived time of skin stimulation. His results are among the most controversial experiments at the interface between psychology and philosophy. The new element that I bring to this discussion is a reanalysis of Libet's raw data. Libet's original data were difficult to interpret because of the manner in which they were presented in tables. Plotting the data as psychometric functions shows that the observers have great uncertainty about the relative timing of events, as seen the shallow psychometric slopes. A second indication of uncertainty comes from Libet's use of three response categories, A first; B first; and A and B simultaneous. The large number of "perceptually simultaneous" responses provides a further measure of the difficulty of the judgment. There are thus a very broad range of stimulus delays in which the subject is unable to make an accurate ordering response. These points provide evidence that there is no compelling reason to invent exotic or ad hoc mechanisms to account for Libet's data since the uncertainty window is large enough to allow simple mechanism such as memory shifts. Libet argued that his data provide evidence for a backward referral in time. I argue that even though Libet's own data are weak, there are good arguments for a backward referral mechanism to help the subject make sense out of the tangled chaos of asynchronous information associated with experienced events.

Cerebral Cortex↗
PubMed1997

Evidence for distinct serine protease activities with a potential role in processing the sperm protein fertilin.

The guinea pig sperm protein fertilin (previously termed PH-30) plays an important role in sperm-egg fusion, and was the first recognized membrane-anchored metalloprotease/disintegrin protein. Fertilin is a heterodimeric glycoprotein which undergoes at least two distinct proteolytic processing steps. Fertilin alpha is processed first, in the testis, whereas fertilin beta is processed separately during sperm maturation in the epididymis. The final processing of fertilin beta occurs immediately adjacent to its predicted integrin ligand domain, and exposes an epitope recognized by a fusion blocking monoclonal antibody. Here, we demonstrate that one or more serine protease activities associated with testicular sperm can process fertilin beta in vitro in a fashion that closely mimics the processing pattern observed in vivo during epididymal sperm maturation. In contrast, several proteases that were added to testicular sperm did not mimic the pattern observed in vivo. These findings raise the intriguing possibility that a fertilin beta converting protease(s) active in vivo may originate from sperm, instead of from the epididymal epithelium. Further, we show that fertilin alpha is most likely processed intracellularly in the secretory pathway based on three observations: (i) only processed fertilin alpha, but not the precursor pro-alpha can be cell-surface biotinylated; (ii) some processed fertilin alpha is sensitive to endoglycosidase H, suggesting cleavage occurs prior to the medial Golgi apparatus; (iii) a reanalysis of the N-terminus of processed fertilin alpha showed that the proteolytic cleavage site is next to four arginine residues, a consensus sequence for intracellular subtilysin type pro-protein convertases. The N-terminal sequence analysis further showed that processed fertilin alpha contains an intact membrane anchored disintegrin domain, and not a truncated disintegrin domain as reported previously (Blobel, C. P., Wolfsberg, T. G., Turck, C. W., Myles, D. G., Primakoff, P., and White, J. M., Nature 356, 248-252, 1992). Proteolytic processing is thought to play an important role in regulating the function of fertilin, and the present study represents a first step toward a better understanding of protease activities involved in the maturation of fertilin, and potentially other sperm surface proteins.

ADAM Proteins↗
PubMed1998

On the interpretation of the shortening of the G1-phase by overexpression of cyclins in mammalian cells.

Increasing the concentration of cyclins in mammalian cells leads to a shortening of the G1-phase of the division cycle. This observation has been interpreted as indicating that these cyclins act during, and are rate limiting for, passage through the G1-phase. Here it is argued that it is not possible to interpret experiments involving cyclin overexpression-induced changes in the lengths of individual cell cycle phases without considering changes in the overall cellular growth rate. A rigorous reanalysis of these experiments demonstrates that the results are consistent with the proposal that the shortening of the G1-phase is merely due to an increase in the rate of mass synthesis in all phases of the cell cycle. Increased cyclin concentrations leads to a faster rate of mass synthesis and a concomitant shortening of the G1-phase. Cyclins can also affect the length of the S- and G2-phases, which leads to the observed shortening of the G1-phase. Thus, the experiments on cyclin overexpression and their effect on G1-phase length cannot be used to support the proposal that cyclins act specifically during the G1-phase of the division cycle.

Animals↗
PubMed1995

The effect of body weight on tumor incidence and carcinogenicity testing in B6C3F1 mice and F344 rats.

Associations between animal body weights and tumor incidence were examined using individual control animal data from 55 mouse and 53 rat studies conducted by the National Toxicology Program. Several statistically significant associations were found, the strongest of which were positive relationships between body weight and risk of liver tumors in both sexes of mice, pituitary gland tumors in both sexes of rats, and mammary gland tumors in female rats. The most compelling evidence that these relationships were causal in nature was the replication of the correlations across individual experiments. In addition, significant correlations between tumor occurrence and body weights occurred in animals as young as 9 weeks of age. Logistic regression models relating 12-month body weight to tumor risk were developed for the strongest relationships, and utilized in the reanalysis of tumor data from two National Toxicology Program studies with treatment-related decreases in body weight. A simulation study based on the logistic regression models indicated that statistical power to detect a treatment-related increase in tumor incidence can be seriously diminished when mean body weight in treated animals is depressed by as little as 10%. Conversely, when mean body weight in control animals is 10% lower than that of treated animals, false positive rates can increase to 20-30%. The severity of the effects of such commonly observed treatment-related disparities in body weight suggests that alternative data analysis methods or experimental designs should be considered to address this potential problem in carcinogenicity testing.

Animals↗
PubMed1996

Tamoxifen in platinum-refractory ovarian cancer: a Gynecologic Oncology Group Ancillary Report.

There is a critical need to find additional effective therapies in the management of ovarian cancer. A previously reported Gynecologic Oncology Group trial demonstrated that tamoxifen is an active drug when used in the salvage setting in this malignancy. Unfortunately, this original report did not specifically examine the utility of tamoxifen in patients with clinically defined platinum-refractory disease. In this reanalysis of the results of treatment of 102 evaluable patients entered into this multi-institutional trial, an objective response rate of 13% (95% confidence interval, 6.4-22.6%) was observed in patients with cisplatin-refractory ovarian cancer. The median response duration in this patient population was 4.4 months (range 1.2-9.2 months). Although the response rate is modest, this well-tolerated hormonal agent is a reasonable therapeutic option in selected patients with ovarian cancer when salvage therapy is to be considered. A possible role for this hormonal agent in other clinical settings in ovarian cancer will need to be defined through the conduct of carefully designed randomized clinical trials.

Antineoplastic Agents, Hormonal↗
PubMed1994

Clouds, hazes, and the stratospheric methane abundance in Neptune.

Analysis of high-spatial-resolution (approximately 0.8 arcsec) methane band and continuum imagery of Neptune's relatively homogeneous Equatorial Region yields significant constraints on (1) the stratospheric gaseous methane mixing ratio (fCH4,s), (2) the column abundances and optical properties of stratospheric and tropospheric hydrocarbon hazes, and (3) the wavelength-dependent single-scattering albedo of the 3-bar opaque cloud. From the center-to-limb behavior of the 7270-angstroms and 8900-angstrom sCH4 bands, the stratospheric methane mixing ratio is limited to fCH4,s < 1.7 x 10(-3), with a nominal value of fCH4,s = 3.5 x 10(-4), one to two orders of magnitude less than pre-Voyager estimates, but in agreement with a number of recent ultraviolet and thermal infrared measurements, and largely in agreement with the tropopause mixing ratio implied by Voyager temperature measurements. Upper limits to the stratospheric haze mass column abundance and 6190-angstroms and 8900-angstroms haze opacities are 0.61 microgram cm-2 and 0.075 and 0.042, respectively, with nominal values of 0.20 microgram cm-2 and 0.025 and 0.014 for the 0.2-micrometer radius particles preferred by the recent Voyager PPS analysis of Pryor et al. (1992, Icarus 99, 302-316). The tropospheric CH4 haze opacities are comparable to that found in the stratosphere, upper limits of 0.104 and 0.065 at 6190 angstroms and 8900 angstroms, respectively, with nominal values of 0.085 and 0.058. This indicates a column abundance less than 11.0 micrograms cm-2, corresponding to the methane gas content within a well-mixed 3% methane tropospheric layer only 0.1 cm thick near the 1.5-bar CH4 condensation level. Constraints on the single-scattering albedos of these hazes include (1) for the stratospheric component, 6190-angstroms and 8900-angstroms imaginary indices of refraction less than 0.047 and 0.099, respectively, with 0.000 (conservative scattering) being the nominal value at both wavelengths, and (2) CH4 haze single-scattering albedos greater than 0.85 and 0.50 at these two wavelengths, with conservative scattering again begin the preferred value. However, conservative scattering is ruled out for the opaque cloud near 3 bars marking the bottom of the visible atmosphere. Specifically, we find cloud single-scattering albedos of 0.915 +/- 0.006 at 6340 angstroms, 0.775 +/- 0.012 at 7490 angstroms, and 0.803 +/- 0.010 at 8260 angstrom. Global models utilizing a complete global spectrum confirm the red-absorbing character of the 3-bar cloud. The global-mean model has approximately 7.7 times greater stratospheric aerosol content then the Equatorial Region. An analysis of stratospheric haze precipitation rates indicates a steady-state haze production rate of 0.185-1.5 x 10(-14) g cm-2 sec-1, in agreement with recent theoretical photochemical estimates. Finally, reanalysis of the Voyager PPS 7500-angstroms phase angle data utilizing the fCH4,s value derived here confirms the Pryor et al. result of a tropospheric CH4 haze opacity of a few tenths in the 22-30 degrees S latitude region, several times that of the Equatorial Region or of the globe. The factor-of-10 reduction in fCH4,s below that assumed by Pryor et al. implies decreased gas absorption and consequently a decrease in the forward-scattering component of tropospheric aerosols.

Aerosols↗
PubMed2000

Synergism of mutations in bacteriophage Qbeta RNA affecting host factor dependence of Qbeta replicase.

We have recently shown that Escherichia coli cells deficient in Hfq protein (i.e. the Qbeta "host factor") support bacteriophage Qbeta replication inefficiently, but that the phage evolves rapidly in the mutant host to become essentially host factor independent. An identical set of four point mutations was identified as being responsible for the adapted phenotype in each of three independent adaptation experiments. Here we report the effects of the single mutations and of some of their combinations on host factor dependence of phage multiplication in vivo and of phage RNA replication by Qbeta replicase in vitro. We find that each single substitution produces only small effects, but that in combination the four mutations synergistically account for most of the observed adaptation of the evolved phages. Surprisingly, a reanalysis of the 3'-terminal sequence of the adapted phages resulted in the discovery of a fifth mutation in all three independently evolved phage populations, namely, a C to U residue transition at nucleotide 4214. This mutation had been missed previously because of its location only three nucleotides from the 3'-end. It appears to contribute little to the Hfq independence but may enhance RNA stability by re-establishing the possibility of forming a long-range base-pairing interaction involving the immediate 3'-terminal sequence.

Allolevivirus↗
PubMed1998

New High-Resolution Analysis of the nu3, nu4, and nu6 Bands of D2CO Measured by Fourier Transform Spectroscopy

A reanalysis of the nu3, nu4, and nu6 interacting bands of D2CO has been carried out in the region 850-1250 cm-1 using high-resolution Fourier transform spectra recorded at Giessen. As compared to the previous study of these bands (1987, K. Nakagawa, R. H. Schwendeman, and J. W. C. Johns, J. Mol. Spectrosc. 122, 462-476) higher J and Ka transitions were assigned for the three bands, leading to a better determination of the upper state constants. The v3 = 1, v4 = 1, and v6 = 1 experimental energy levels were introduced in a least-squares fit calculation together with the microwave measurements available in the literature in order to obtain the upper state parameters (band centers, rotational and coupling constants). In this calculation, which allowed us to reproduce both the infrared and the microwave measurements to within their experimental accuracies, the A-, B-, and C-type Coriolis interactions involving the rotational levels belonging to the v4 = 1 and v6 = 1, v3 = 1 and v4 = 1, and v3 = 1 and v6 = 1 interacting states respectively were explicitly taken into account. Finally, from the intensities, a new determination of the relative values of the q3, q4, and q6 first derivatives of the D2CO dipole moment was performed. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗
PubMed1998

Fourier Transform Emission Spectroscopy of the A2Pi-X2Sigma+ Transition of BeD.

The A2Pi-X2Sigma+ Deltav = 0 sequence of BeD was observed in the 19 500-20 800 cm-1 spectral region using a Fourier transform spectrometer. The emission spectrum was excited in a Be hollow cathode discharge lamp with a He/D2 gas mixture. The observed lines were assigned to the 0-0 to 6-6 bands. The Deltav = -1 sequence was too weak to be seen in our Fourier transform spectra. We therefore used a previously recorded but unpublished arc emission spectrum to identify the 0-1 to 5-6 Deltav = -1 bands. Consequently, all of the diagonal bands could be linked together and the vibrational intervals determined. The Deltav = 0 and Deltav = -1 data were fitted together in a global fit and effective constants derived. Using the information available from the study of the C2Sigma+-X2Sigma+ system [R. Colin, C. Drèze, and M. Steinhauer, Can. J. Phys. 61, 641 (1983)], the v = 8-12 vibrational levels of the ground state were added in a Dunham fit. A set of Dunham Y constants was determined for the X2Sigma+ state along with traditional equilibrium parameters for the A2Pi excited state. The equilibrium bond lengths were found to be 1.341742(5) Å for the ground state and 1.33309(4) Å for the excited state. A reanalysis of the previously published A2Pi-X2Sigma+ 0-0 to 3-3 Deltav = 0 bands of BeT [D. De Greef and R. Colin, J. Mol. Spectrosc. 53, 455-465 (1974)] was also performed. Copyright 1998 Academic Press.

Journal Article↗
PubMed1999

New Rotational Analysis of the B2Sigma+-X2Sigma+ Bands in 69Ga16O and 71Ga16O.

In the emission spectrum of the Ga16O molecule, the 0-0 and 1-0 bands of the B-X system have been rephotographed by means of conventional high-resolution spectroscopy. Clear resolution on the rotational structure near the band origins made it possible to perform reanalysis of the bands and derive new molecular constants characterizing 69Ga16O and 71Ga16O in the B2Sigma+ and X2Sigma+ states. Copyright 1999 Academic Press.

Journal Article↗
PubMed2001

Rovibrational Study of the CH(2) Wagging Fundamental of Monofluoroacetonitrile.

The vapor-phase infrared spectrum of monofluoroacetonitrile (CH(2)FCN) has been recorded at high resolution in the nu(4) band region (1363-1398 cm(-1)) using a tunable diode laser spectrometer. A detailed assignment of the rotational structure of the expected a-/b-hybrid band has been made for a-type transitions with K(a)</=19, J</=61. The b-type transitions were too weak to be observed. Upper state spectroscopic constants including the sextic terms have been obtained from a set of unperturbed data employing the Watson A-reduced Hamiltonian in the I(r) representation. A number of perturbed transitions have been accounted for, including b- and c-type Coriolis resonances and anharmonic resonances between nu(4) and the nearby levels nu(5)+nu(12) and nu(11)+nu(12). The vibrational energies of these perturbing levels have been obtained from the reanalysis of the low-resolution infrared spectrum. Rotational constants and the band origin of the perturbers along with the interaction parameters with the v(4)=1 state have also been determined. Copyright 2001 Academic Press.

Journal Article↗
PubMed1994

DNA repair and the evolution of longevity: a critical analysis.

Comparative gerontologists argue that variation among species in DNA repair rates may explain differences in maximum lifespan, and support this claim with the observation that DNA repair rates and lifespan correlate positively among mammals. However, these findings may be confounded by both size and phylogeny. Repair rates and lifespan may be positively correlated because both are positively correlated with body size. In addition, previous comparative studies have not controlled for the potentially confounding effects of phylogeny. In this study, I elucidate why we might expect larger species to have higher DNA repair rates, independent of differences in lifespan, and use existing data to test whether the relationship between DNA repair rates and lifespan holds up after controlling for the potentially confounding effects of size and phylogeny. Reanalysis of the existing data suggests that there is little comparative evidence in favour of the hypothesis relating DNA repair rates and lifespan.

Animals↗
PubMed2000

Apparent galactose appearance rate in human galactosemia based on plasma [(13)C]galactose isotopic enrichment.

Determination of endogenous galactose formation in galactosemic subjects provides important information in understanding the etiology of the long-term complications. To accomplish this task a sensitive method for measurement of isotopic enrichment of plasma galactose was developed. The aldononitrile pentaacetate derivative of galactose was utilized for gas chromatography/mass spectrometry analysis. Using a phenyl-methylsilicone capillary column, adequate separation of galactose from glucose was obtained by temperature programming of the chromatography. The specific fragmentation pattern of m/z 212, 225, 314 from d-[(12)C]galactose and m/z 213, 226, 315 from l-[(13)C]galactose was used for the galactose enrichment measurement by atom percent excess (APE). There was good correlation between expected enrichment and determined APEs at galactose concentrations of 1, 2, and 5 micromol/L with a coefficient of variation ranging from 0.22 to 7.17%. The method provides an accurate estimation of plasma [(13)C]galactose enrichment from which the galactose production rate can be calculated. The steady-state plasma l-[(13)C]galactose isotopic enrichment of three individuals with galactosemia, two males ages 33 and 13, and one female age 9, during constant infusion of l-[(13)C]galactose was 55, 41, and 55%, allowing the estimation of the apparent galactose appearance rate of 0.62, 1.09, and 0.82 mg/kg/h, respectively. The reanalysis of three previous studies by the present method found that APE values determined by the method then employed, butylboronate acetate derivatization, were systemically lower than those determined with aldononitrile pentaacetate derivatization, making for an overestimation of the apparent galactose appearance rate. The small plasma sample volumes needed make it feasible to perform these studies in infants and young children with galactosemia.

Carbon Isotopes↗
PubMed2000

5'-UTR structural organization, transcript expression, and mutational analysis of the human Rab geranylgeranyl transferase alpha-subunit (RABGGTA) gene.

Hermansky-Pudlak syndrome (HPS) is a recessively inherited disease with dysfunction of several related subcellular organelles including platelet-dense granules, melanosomes, and lysosomes. Our recent identification of the mutation in murine Rab geranylgeranyl transferase alpha-subunit gene (Rabggta) in one mouse model of HPS, the gunmetal mouse, suggested that human patients with similar phenotypes might have mutations in the human orthologous RABGGTA gene. This prompted reanalysis of the 5'-untranslated structure of the human RABGGTA gene in normal individuals and in patients with deficiencies of platelet-dense granules (alphadelta-SPD), alpha granules (alpha-SPD or gray platelet syndrome, GPS) or alpha plus dense granules (alphadelta-SPD). We report the complete sequence of intron alpha of RABGGTA and demonstrate that exon alpha is immediately upstream of intron alpha. The exon/intron structural organization of the 5'-untranslated region (UTR) of human RABGGTA was found to be similar to that of the mouse Rabggta gene. However, exons alpha and introns alpha are not homologous between mouse and human. Features of the 5'-UTR of RABGGTA suggest it is a housekeeping gene. While obvious disease-causing mutations of human RABGGTA were not found in our existing SPD patients by sequencing its entire coding region, several polymorphisms of RABGGTA including a putative cryptic splicing mutation in intron 4 were identified. Knowledge of the 5'-UTR structure of RABGGTA and its common polymorphisms will be useful for mutation screening or linkage analysis in patients with albinism, thrombocytopenia, or platelet SPD.

5' Untranslated Regions↗
PubMed1994

Multiple origins of colonial green flagellates from unicells: evidence from molecular and organismal characters.

Phylogenetic hypotheses generated from cladistic analysis of organismal and molecular data are shown to be generally congruent and/or complementary for comparisons of unicellular and colonial green algae in the Chlorophyceae. Cladistic analysis of organismal character data corroborates the alliance of colonial Stephanosphaera with unicellular Haematococcus (Haematococcaceae sensu Smith), inferred from previous studies of nuclear-encoded rRNA sequence data. The organismal data also support monophyly of the colonial Volvocaceae (sensu Smith). Alliances of other unicellular taxa, including those ascribed to the "Euchlamydomonas" Hauptgruppe (sensu Ettl), are not resolved by organismal characters principally because the structure of the data is skewed to shared ancestral characters (symplesiomorphies) and unique characters (autapomorphies) which define individual taxa only. Reanalysis of rRNA sequence data, with additional sequence data for critical taxa, does not support monophyly of the colonial Volvocaceae (sensu Smith). However, these data are weak in the support of the alternate hypothesis of nonmonophyly. In contrast, relationships among most unicellular flagellates are unambiguously resolved by the molecular data. Although the failure of the sequence data to resolve relationships among colonial flagellates appears to be due to a sampling of conservative sequences, an ancient, rapid radiation event or taxon sampling bias may also be contributing to the ambiguity problem. Results from analysis of a combined data set (organismal and molecular) are generally consistent with the inferences of the organismal character data regarding the colonial flagellates and are also consistent with the inferences of the sequence data regarding the unicellular taxa.

Animals↗
PubMed1999

Molecular phylogenetics, tRNA evolution, and historical biogeography in anguid lizards and related taxonomic families.

Phylogenetic relationships among lizards of the families Anguidae, Anniellidae, Xenosauridae, and Shinisauridae are investigated using 2001 aligned bases of mitochondrial DNA sequence from the genes encoding ND1 (subunit one of NADH dehydrogenase), tRNA(Ile), tRNA(Gln), tRNA(Met), ND2, tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), tRNA(Tyr), and COI (subunit I of cytochrome c oxidase), plus the origin for light-strand replication (O(L)) between the tRNA(Asn) and the tRNA(Cys) genes. The aligned sequences contain 1013 phylogenetically informative characters. A well-resolved phylogenetic hypothesis is obtained. Because monophyly of the family Xenosauridae (Shinisaurus and Xenosaurus) is statistically rejected, we recommend placing Shinisaurus in a separate family, the Shinisauridae. The family Anniellidae and the anguid subfamilies Gerrhonotinae and Anguinae each form monophyletic groups receiving statistical support. The Diploglossinae*, which appears monophyletic, is retained as a metataxon (denoted with an asterisk) because its monophyly is statistically neither supported nor rejected. The family Anguidae appears monophyletic in analyses of the DNA sequence data, and statistical support for its monophyly is provided by reanalysis of previously published allozymic data. Anguid lizards appear to have had a northern origin in Laurasia. Taxa currently located on Gondwanan plates arrived there by dispersal from the north in two separate events, one from the West Indies to South America and another from a Laurasian plate to Morocco. Because basal anguine lineages are located in western Eurasia and Morocco, formation of the Atlantic Ocean (late Eocene) is implicated in the separation of the Anguinae from its North American sister taxon, the Gerrhonotinae. Subsequent dispersal of anguine lizards to East Asia and North America appears to have followed the Oligocene drying of the Turgai Sea. The alternative hypothesis, that anguine lizards originated in North America and dispersed to Asia via the Bering land bridge with subsequent colonization of Europe and Morocco, requires a phylogenetic tree seven steps longer than the most parsimonious hypothesis. North African, European, and West Asian anguines were isolated from others by the rapid uplift of Tibet in the late Oligocene to Miocene. Phylogenetic analysis of evolutionary changes in the gene encoding tRNA(Cys) suggests gradual reduction of dihydrouridine (D) stems by successive deletion of bases in some lineages. This evolutionary pattern contrasts with the one observed for parallel elimination of the D-stem in mitochondrial tRNAs of eight other reptile groups, in which replication slippage produces direct repeats. An unusual, enlarged TpsiC (T) stem is inferred for tRNA(Cys) in most species.

Animals↗
PubMed2002

Aging and cholinergic modulation of the transient magnetic 40-Hz auditory response.

Cholinergic blockade by scopolamine, a central muscarinic receptor antagonist, may produce transient memory impairment in healthy subjects, and it has been used as a neurochemical model of cognitive degeneration in aged individuals. To observe the muscarinic modulation of memory and cortical auditory processing, nine cognitively intact elderly subjects (59-80 years) were studied using neuropsychological tests and 122-channel magnetoencephalography (MEG) after an administration of scopolamine hydrobromide (0.3 mg, i.v.) or glycopyrrolate (0.2 mg, i.v.), a peripheral muscarinic antagonist. A double-blind randomized crossover design was used in two sessions separated by at least 1 week. Scopolamine, but not glycopyrrolate, produced a transient impairment of verbal memory performance in the elderly subjects. MEG indicated that the auditory-evoked 40-Hz magnetic response was significantly larger after scopolamine than after glycopyrrolate administration. Furthermore, reanalysis of our earlier results in younger subjects (20-31 years), basically supporting the present MEG findings, tentatively suggests that the scopolamine effects on the 40-Hz response may be slightly pronounced with aging. In sum, the transient magnetic 40-Hz auditory response may be useful in studies on brain cholinergic deficits in elderly subjects.

Aged↗