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PubMed2001

Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism.

The anxiolytic effects of aniracetam have not been proven in animals despite its clinical usefulness for post-stroke anxiety. This study, therefore, aimed to characterize the anxiolytic effects of aniracetam in different anxiety models using mice and to examine the mode of action. In a social interaction test in which all classes (serotonergic, cholinergic and dopaminergic) of compounds were effective, aniracetam (10-100 mg/kg) increased total social interaction scores (time and frequency), and the increase in the total social interaction time mainly reflected an increase in trunk sniffing and following. The anxiolytic effects were completely blocked by haloperidol and nearly completely by mecamylamine or ketanserin, suggesting an involvement of nicotinic acetylcholine, 5-HT2A and dopamine D2 receptors in the anxiolytic mechanism. Aniracetam also showed anti-anxiety effects in two other anxiety models (elevated plus-maze and conditioned fear stress tests), whereas diazepam as a positive control was anxiolytic only in the elevated plus-maze and social interaction tests. The anxiolytic effects of aniracetam in each model were mimicked by different metabolites (i.e., p-anisic acid in the elevated plus-maze test) or specific combinations of metabolites. These results indicate that aniracetam possesses a wide range of anxiolytic properties, which may be mediated by an interaction between cholinergic, dopaminergic and serotonergic systems. Thus, our findings suggest the potential usefulness of aniracetam against various types of anxiety-related disorders and social failure/impairments.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2004

Experimental evidence for sympatric ecological diversification due to frequency-dependent competition in Escherichia coli.

We investigate adaptive diversification in experimental Escherichia coli populations grown in serial batch cultures on a mixture of glucose and acetate. All 12 experimental lines were started from the same genetically uniform ancestral strain but became highly polymorphic for colony size after 1000 generations. Five populations were clearly dimorphic and thus serve as a model for an adaptive lineage split. We analyzed the ecological basis for this dimorphism by studying bacterial growth curves. All strains exhibit diauxie, that is, sequential growth on the two resources. Thus, they exhibit phenotypic plasticity, using mostly glucose when glucose is abundant, then switching to acetate when glucose concentration is low. However, the coexisting strains differ in their diauxie pattern, with one cluster in the dimorphic populations growing better in the glucose phase, and the other cluster having a much shorter lag when switching to the acetate phase. Using invasion experiments, we show that the dimorphism of these two ecological types is maintained by frequency-dependent selection. Using a mathematical model for the adaptive dynamics of diauxie behavior, we show that evolutionary branching in diauxie behavior is a plausible theoretical scenario. Our results support the hypothesis that, in our experiments, adaptive diversification from a genetically uniform ancestor occurred due to frequency-dependent ecological interactions. Our results have implications for understanding the evolution of cross-feeding polymorphism in microorganisms, as well as adaptive speciation due to frequency-dependent selection on phenotypic plasticity.

Adaptation, Physiological↗

PubMedDate not supplied

The influence of high-frequency stimulation of the midbrain reticular formation on the interaction of neurons of the neocortex.

The influence of the stimulation of the midbrain reticular formation (NRT) at a frequency of 75-100 Hz, current strength 33-400 microA, on the interaction of neurons of the visual and sensorimotor areas of the neocortex of rabbits was investigated. Cross- and autocorrelation histograms of the impulse sequences were plotted. Stimulation of the NRT led to an increase in the number of pairs of neurons functioning in correlation and an increase in the probability of discharges of neurons one after the other with delays from 100 to 400 msec as compared with resting wakefulness. The mechanisms of the interaction of the cells were not altered in the process. Comparison with previously obtained data made it possible to conclude that activation of the NRT may lead to specific changes in the interaction of neurons which are observable during pseudoconditioning and at the beginning of the development of a conditioned reflex.

Animals↗

PubMed2005

Vibrational characteristics of carbon nanotubes as nanomechanical resonators.

Using eigenvalue analysis of mass and stiffness matrices directly computed from atomistic simulations, natural frequencies and mode shapes of various carbon nanotubes are studied. The stiffness matrix was developed from the Tersoff-Brenner potential for carbon-carbon interactions. The computed frequencies of the radial breathing modes of a variety of armchair (n, n) nanotubes agree well with results obtained by others using different techniques. In addition, the study reveals diverse mode shapes such as accordion-like axial modes, lateral bending modes, torsional modes, axial shear modes, and radial breathing modes for a variety of single-wall, multi-wall, and bamboo-type carbon nanotubes. The effects of different constraints on the carbon nanotube ends on the computed frequencies and mode shapes have been investigated for possible applications in vibration sensors or electromechanical resonators.

Computer Simulation↗

PubMed1999

Word frequency, repetition, and lexicality effects in word recognition tasks: beyond measures of central tendency.

Response time (RT) distributions obtained from 3 word recognition experiments were analyzed by fitting an ex-Gaussian function to the empirical data to determine the main effects and interactive influences of word frequency, repetition, and lexicality on the nature of the underlying distributions. The ex-Gaussian analysis allows one to determine if a manipulation simply shifts the response time (RT) distribution, produces a skewing of the RT distribution, or both. In contrast to naming performance, the lexical decision results indicated that the main effects and interactions of word frequency, repetition, and lexicality primarily reflect increased skewing of the RT distributions, as opposed to simple shifts of the RT distributions. The implications of the results were interpreted within a hybrid 2-stage model of lexical decision performance.

Adult↗

PubMed1998

High-Frequency/High-field electron spin echo envelope modulation study of nitrogen hyperfine and quadrupole interactions on a disordered powder sample

High-frequency/high-field (95 GHz/3.4 T) electron spin echo envelope modulation (ESEEM) experiments on single crystals and disordered samples of dianisyl-nitroxide (DANO) radicals are reported. At these high microwave frequencies (W-band), the anisotropic g-matrix of the nitroxide radical is resolved in the EPR spectrum. Additionally ESEEM modulations from other than nitrogen nuclei, such as protons, are highly suppressed at these frequencies, because they are too far from the cancellation condition for effective mixing of the nuclear spin functions. Therefore the nitrogen (14N) hyperfine and quadrupole coupling tensors could be determined without ambiguity from powder measurements. The results obtained were checked by ESEEM measurements on single crystals. Advantages and disadvantages of high-field ESEEM on nitrogen couplings are briefly discussed and compared with electron nuclear double resonance (ENDOR) and X-band ESEEM. Copyright 1998 Academic Press.

Journal Article↗

PubMed1976

Manganese(II) and substrate interaction with unadenylylated glutamine synthetase (Escherichia coli w). I. Temperature and frequency dependent nuclear magnetic resonance studies.

A comprehensive study of solvent interaction with unadenylylated glutamine synthetase (E1.7) has been conducted using the enzyme isolated from Escherichia coli W. The longitudinal, (1/T1p)b, and transverse, (1/T2p)b, proton relaxation rates were measured with various enzyme samples as a function of frequency (6-48 MHZ) and temperature (1-40 degrees C). With Mn(II) bound at the "tight" metal ion site approximately two water molecules are rapidly exchanging with bulk solvent. This number is reduced to approximately one in the presence of glutamine. All data were successfully analyzed according to the Solomon-Bloembergen-Morgan (SBM) scheme for dipolar relaxation of water protons interacting with enzyme-bound Mn(II). The correlation time for this process varies from 1 to 3 X 10(-9) for the complexes described above. Significant contributions to the correlation time arise from both 1/taum, the exchange rate for water molecules bound at the metal site, and from 1/taus, the electron spin relaxation rate for Mn(II) with the latter rate showing a frequency dependence at the magnetic field strengths used in this study. A study of Mn(II) binding to E1.7 at 25 degrees C revealed two classes of metal ion sites, a "tight" set of one per subunit with KD=5.0 X 10(-7) M and a "weak" set of one per subunit with KD=4.5 X10(-5)M. In the presence of glutamine the affinity of the first site for Mn(II) was unchanged but the KD value for the weak site changed to 3 X 10(-6)M. In E1.7 samples with Mn(II) bound at both the tight and weak metal ion sites the data are interpretable with two rapidly exchanging water molecules interacting with each bound Mn(II)ion. With saturating amounts of glutamine or of ADP or of glutamine plus ADP plus arsenate, the proton relaxation rates progressively decreased suggesting that the substrates or inhibitors used were interacting with the bound Mn(II) ions resulting in diminished solvent accessibility to these bound ions. These results are interpretable in terms of ligand substitution into the coordination sphere of the bound Mn(II) ions. Indeed this is probably the case for Mn(II) at the weak metal ion site since Hunt et al. ((1975), Arch. Biochem. Biophys. 166, 102) showed that Mn(II) can bind as the Mn(II)-ADP complex to the second metal ion site. Results of proton relaxation rate data on E1.7 with Mn(II) bound at both the tight and weak metal ion sites led to the conclusion that these metal ion sites are greater than 6 A apart. In comparison with proton relaxation rate data on fully adenylylated glutamine synthetase (E11.8) as studied by Villafranca and Wedler ((1974), Biochemistry 13, 3286), the first "tight" metal ion site in E11.8 has three rapidly exchanging water molecules. Mn(II) has a weaker binding constant to E11.8 (KD approximately 5 X 10(-6)M) at the pH value used in both studies and a suggestion is made that an additional protein ligand is binding to Mn(II) in glutamine synthetase when the subunits are not adenylylated.

Adenine Nucleotides↗

PubMedDate not supplied

Symbolic play language during sensory integration treatment.

OBJECTIVE: Clinical writings on sensory integration treatment and theory have long professed that play serves as an important means of implementing treatment goals. However, to date, there has been little research that examines this aspect of the intervention. With the use of play language as an indicator for the occurrence of play, this study examined the frequency and characteristics associated with symbolic play language that therapists and children use during sensory integration therapy. This study is part of an ongoing research program designed to examine therapist-child interactions. METHOD: The frequency of symbolic play language observed in 41 videotaped treatment sessions of therapist-child dyads (21 children, 12 therapists) was recorded with the Challenge Coding System. The presence of symbolic play language was recorded if the child or therapist used language that incorporated the child, therapist, equipment, or activity into a symbolic or pretend play theme. The frequency of symbolic play language and percentage of time spent using play language were calculated. Associations among frequency of play language, child age, and behavior during the session (e.g., seeking assistance, cooperation) were also examined. RESULTS: Symbolic play language proved to be a major feature of sensory integration treatment sessions. It also correlated with child age and with some features associated with therapeutic interactions (i.e., child tries hard, child seeks assistance, therapist assists child, therapist modifies activity, therapist structures activity). CONCLUSION: The results suggest that these therapists used play language frequently and that this usage may support children in sensory integrative therapy to successfully accomplish activities.

Child↗

PubMed1991

Local circuit synaptic interactions between CA1 pyramidal cells and interneurons in the kainate-lesioned hyperexcitable hippocampus.

Following kainate (KA)-induced lesions of subfield CA3--a lesion relevant to human temporal lobe epilepsy--remaining pyramidal cells in CA1 display synchronous hyperexcitability associated with a loss of synaptic inhibition. Despite this loss, inhibitory interneurons in CA1 remain viable, and the density and function of GABAergic receptors on the CA1 pyramidal cells are maintained at approximately normal levels. To further evaluate inhibition in this system, the authors examined interactions between pyramidal cells and inhibitory interneurons in paired intracellular recordings. Recordings were carried out in rat hippocampal slices 2-4 weeks following bilateral intraventricular KA injections. The frequency of synaptic interactions between CA1 basket cells and pyramidal cells was lower in hyperexcitable slices than in controls; both synapses in the recurrent inhibitory circuit appeared to be involved. No recurrent excitatory interactions were seen between pyramidal cell pairs in lesioned or normal slices. The weakened interconnections between pyramidal cells and interneurons are consistent with the decreased inhibition previously found in this model. Unexpectedly, strong stimulation, which may directly activate local inhibitory circuitry, was effective in reducing hyperexcitability in KA-lesioned slices. These data suggest that development of recurrent excitatory connections among CA1 hippocampal pyramidal cells contribute little to tissue excitability, and support the hypothesis that a functional uncoupling between inhibitory interneurons and CA1 pyramidal cells is responsible for the seizure-like activity typical of KA-lesioned hippocampus. The data are also consistent with the hypothesis that in the KA model, the structural circuitry needed for inhibition in CA1 is maintained, and can be functionally activated by appropriate stimuli.

Animals↗

PubMed2004

Low spatial frequencies are suppressively masked across spatial scale, orientation, field position, and eye of origin.

Masking is said to occur when a mask stimulus interferes with the visibility of a target (test) stimulus. One widely held view of this process supposes interactions between mask and test mechanisms (cross-channel masking), and explicit models (e.g., J. M. Foley, 1994) have proposed that the interactions are inhibitory. Unlike a within-channel model, where masking involves the combination of mask and test stimulus within a single mechanism, this cross-channel inhibitory model predicts that the mask should attenuate the perceived contrast of a test stimulus. Another possibility is that masking is due to an increase in noise, in which case, perception of contrast should be unaffected once the signal exceeds detection threshold. We use circular patches and annuli of sine-wave grating in contrast detection and contrast matching experiments to test these hypotheses and investigate interactions across spatial frequency, orientation, field position, and eye of origin. In both types of experiments we found substantial effects of masking that can occur over a factor of 3 in spatial frequency, 45 degrees in orientation, across different field positions and between different eyes. We found the effects to be greatest at the lowest test spatial frequency we used (0.46 c/deg), and when the mask and test differed in all four dimensions simultaneously. This is surprising in light of previous work where it was concluded that suppression from the surround was strictly monocular (C. Chubb, G. Sperling, & J. A. Solomon, 1989). The results confirm that above detection threshold, cross-channel masking involves contrast suppression and not (purely) mask-induced noise. We conclude that cross-channel masking can be a powerful phenomenon, particularly at low test spatial frequencies and when mask and test are presented to different eyes.

Contrast Sensitivity↗

PubMed1998

Effects of video-based staff training with manager-led exercises in residential support.

The effectiveness of video-based staff training with manager-led exercises in improving staff performance in residential support for persons with disabilities was examined. Research staff assisted two residential program managers to implement staff training in health and safety, basic support, and residential support values. Results showed improvement in (a) staff members' washing hands when appropriate, (b) wearing gloves when appropriate, and (c) frequency of positive interactions with residents. These changes in staff behavior maintained over a 6-month follow-up. Following the values training, in one house, brief increases were observed in frequency of residents' community activities. These changes did not maintain. No improvements in these measures were noted in the other house. Implications of these findings for assurance of competent staff performance with residents were discussed.

Adult↗

PubMed1999

Transmitter quantal size in Torpedo electrocytes is determined by frequency of release.

Miniature end-plate potentials (MEPPs) were focally recorded from the cytoplasmic surface of electrocytes in isolated columns of the Torpedo electric organ. Double electrode studies showed that the junctional area was restricted to 12 micron2. MEPP frequencies ranging from 1/min to 400/s were controlled with electrode advancement against the cytoplasmic surface. Stable membrane potentials and noise levels indicated constant intracellular, focal recording conditions. Focal MEPPs are only 1-3 mV and MEPP amplitudes smoothly decreased with an increase in MEPP frequency which demonstrates a process that meters quantal size at moment of release. Thus, release if not from a prepackaged store. MEPP interval analyses showed that events are weakly interactive at low frequencies and periodic at higher frequencies. The interdependency of MEPP amplitudes and intervals indicates that the mechanism of release controls both rate and quantal size. We propose that the amplitude and frequency dependencies of MEPPs at the Torpedo nerve-electrocyte junction are best described by a membrane channel (e.g., mediatophore, Israël and Dunant, Neurochem. Int. 28 (1996) 1-9) that meters transmitter from a presynaptic store.

Animals↗

PubMed2003

Sources and mechanisms of DPOAE generation: implications for the prediction of auditory sensitivity.

Otoacoustic emissions (OAEs) have become a commonly used clinical tool for assessing cochlear health status, in particular, the integrity of the cochlear amplifier or motor component of cochlear function. Predicting hearing thresholds from OAEs, however, remains a research challenge. Models and experimental data suggest that there are two mechanisms involved in the generation of OAEs. For distortion product, transient, and high-level stimulus frequency emissions, the interaction of multiple sources of emissions in the cochlea leads to amplitude variation in the composite ear canal signal. Multiple sources of emissions complicate simple correlations between audiometric test frequencies and otoacoustic emission frequencies. Current research offers new methods for estimating the individual components of OAE generation. Input-output functions and DP-grams of the nonlinear component of the 2f2-f2 DPOAE may ultimately show better correlations with hearing thresholds. This paper reviews models of OAE generation and methods for estimating the contribution of source components to the composite emission that is recorded in the ear canal. The clinical implications of multiple source components are discussed.

Acoustic Stimulation↗

PubMed2006

Imatinib activity in vitro in tumor cells from patients with chronic myeloid leukemia in chronic phase and blast crisis.

The aims of this study were to evaluate the feasibility of using the non-clonogenic fluorometric microculture cytotoxicity assay in drug sensitivity testing of tumor cells from patients with chronic myeloid leukemia. In nine samples (six chronic phase, three blast crisis), the drug sensitivities in tumor cells from blood versus from bone marrow and fresh tumor cells versus cryopreserved were compared. In 26 samples obtained in chronic phase (pretreatment), in six samples from patients in blast crisis and in the K 562 cell line, the activity of imatinib alone and in combination with cytarabine, vincristine, daunorubicin, interferon, arsenic trioxide and homoharringtonine was evaluated. All chronic myeloid leukemia chronic phase samples were sensitive to imatinib, with a mean IC50 at 10.3 mumol/l. The chronic myeloid leukemia samples from blast crisis (n=6) were significantly more sensitive to imatinib than the samples from chronic phase (n=26) (P<0.05), with an IC50 mean at 0.4 mumol/l. In blast crisis samples, significant positive interaction effects were observed between imatinib and all other tested drugs except for interferon. In chronic phase samples, interferon, daunorubicin and arsenic trioxide were the drugs with the highest frequency of positive interactions with imatinib (P<0.05). We conclude that the fluorometric microculture cytotoxicity assay may be a useful method for drug sensitivity testing in chronic myeloid leukemia patient samples from both chronic phase and blast crisis, and that testing primary tumor cells may have advantages over cell line studies. Imatinib shows a higher in vitro activity and more positive drug interactions in cells from blast crisis than chronic phase chronic myeloid leukemia patients. Combinations between imatinib and interferon, daunorubicin and arsenic trioxide may be interesting for future clinical trials in patients with chronic myeloid leukemia chronic phase.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Beyond bereavement support group meetings: exploring outside social contacts among the members.

This article examines the extent to which bereavement support group participants engage in social interaction with fellow group members outside of the meetings, demographic influences on outside contact, and the relationship between this social interaction and bereavement outcomes. Data are presented from a longitudinal study that included 144 recently bereaved spouses between the ages of 51 and 89 who participated in a support group intervention. During the course of the study the majority of the participants had contact with other group members in addition to the scheduled meetings even though the group leaders did not encourage outside contact. Although the frequency of the interaction was only moderate, the support group participants reported feeling relatively close to their fellow group members. Men were as likely as women to have outside contact but they delayed in doing so. Those who engaged in outside contact were slightly more depressed, experienced more stress, and were more lonely at the time of the contact relative to others. Those who maintained some kind of interaction by Time 3 (1 year bereaved), however, reported less loneliness by the end of the study (Time 4). Findings are discussed in terms of the frequency and duration of support group interventions, the gender composition of the groups, and the need to incorporate into future studies a more systematic examination of outside interaction among support group participants.

Aged↗

PubMed1975

[Responses of inferior colliculus neurons to frequency modulated signals and the temporal characteristics of inhibitory interaction].

Comparison of neuronal responses (118 units) in the inferior colliculus of anesthetized rats to frequency-modulated (FM) sounds and time characteristics of two-tone inhibition were carried out. High sensitivity to certain direction of FM in 2/3 of neurons coincide with spatial characteristics of excitatory and nihibitory areas: their shape, width and arrangement. In 1/3 of neurons directional response specificity is shown to be determined by different time course of inhibitory process evoked by high-frequency and low-frequency tones.

Acoustic Stimulation↗

PubMed1984

Cardiac glycosides with different effects in the heart.

Remarkable differences exist between the effects of different cardiac glycosides (native and semi-synthetic) with respect to the affinity and to the magnitude of inotropic responses and their time courses. At glycoside concentrations which lead to identical Na-K-ATPase inhibitions, the inotropic responses vary widely. This finding contradicts the hypothesis that the increase of contractile force is the consequence of an ATPase inhibition and causally related to it. We propose the hypothesis that the inhibition of ATPase and the inotropic stimulation provoked by cardiac glycosides are two parallel events, not causally related but both mediated by the same receptor. The inhibition of the Na-K-ATPase is the consequence of the occupation and thus proportional to the concentration of the glycoside-ATPase complexes. In contrast, the inotropic response is determined by the frequency of glycoside-ATPase-interactions. Glycosides which possess high association and dissociation rate constants will interact with the ATPase with high frequencies and thus will evoke larger inotropic responses at a given ATPase inhibition than glycosides with low turnover rates.

Animals↗

PubMed1990

A combined sensitivity for frequency and interaural intensity difference in neurons in the auditory midbrain of the grassfrog.

The relation between spectral tuning and sensitivity for interaural intensity difference (IID) was studied for single units in the auditory midbrain of the grassfrog. The stimuli consisted of sequences of pure tones of different frequency and interaural intensity differences presented by means of a closed sound system. At best excitatory frequency, three types of binaural interaction were observed: E0 (one ear excitatory 23%), EE (both ears excitatory 9%) and EI (one ear excitatory, the other inhibitory 67%). For a considerable number of units different types of binaural interaction were observed for different stimulus frequencies. More than 30% of the binaural units had multiple excitatory and inhibitory regions in their spectrotemporal selectivity. E0 and EI units had uniformly distributed best frequencies, EE units generally had best frequencies near 1.0 kHz. The E0 and EE categories had response latencies less than about 70 ms whereas EI units could have longer latencies. Most EE and all EI category units had sigmoidally shaped IID-rate curves. About 40% of the units had a combined sensitivity for sound spectrum and IID which was invariant to overall stimulus intensity. For nearly all EI units the inhibitory influence of the ipsilateral ear was confined to frequencies in the 0.4-1.6 kHz range and was not correlated with a unit's best frequency. By means of a simple additive model we demonstrated that determination of sound source laterality can be achieved by ensemble coding in the auditory midbrain.

Action Potentials↗