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At least 1,513 records · Page 84Linked to original sources
PubMed1999

Neurochemical evidence of dopamine release by lateral olivocochlear efferents and its presynaptic modulation in guinea-pig cochlea.

In this study, using an in vitro superfusion technique for the first time, we provide direct neurochemical evidence of the transmitter role of dopamine at the level of lateral olivocochlear efferent fibres of the guinea-pig cochlea. Our results revealed that nerve terminals are able to take up and release dopamine upon axonal stimulation. Since dopamine is thought to protect the afferent nerve fibres from damage due to acoustic trauma or ischaemia, enhancement of the release of dopamine, a potential therapeutic site of these injuries, was investigated. Positive modulation of dopamine release has been shown by a D1 dopamine receptor agonist, an antagonist and piribedil. Furthermore, negative feedback on the stimulation-evoked release of dopamine via D2 dopamine receptors has been excluded. Electrical stimulation of the cochlear tissue produced a significant and reproducible release of [3H]dopamine, which could be blocked by tetrodotoxin (1 microM) and cadmium (100 microM), proving that axonal activity releases dopamine and its dependence on Ca2+ influx verifies its neuronal origin. Nomifensine, a high-affinity dopamine uptake blocker, prevented the tissue from taking up [3H]dopamine from the bathing solution, also indicating the neural origin of dopamine released in response to stimulation. SKF-38393 (a selective D1 agonist) increased both the resting and electrically evoked release of dopamine. Piribedil (a D3/D2/D1 agonist), a drug under investigation, known to prevent acoustic trauma or ischaemia-induced hearing loss, had a similar and concentration-dependent increasing effect on both resting and evoked release of dopamine. The effect of both drugs on stimulation-evoked release could be prevented by SKF-83566 (a selective D1 antagonist). However, SKF-83566 alone enhanced the resting and axonal conduction-associated release of dopamine. D2 agonists and antagonists failed to modulate the release of dopamine, indicating the lack of negative feedback modulation of dopamine release. Our results suggest that the release of dopamine was subjected to modulation by a D1 receptor agonist and an antagonist. In addition, it is concluded that D2 receptors are not involved in the modulation of dopamine release. This observation may have clinical relevance in the prevention or therapy of particular types of hearing loss, because enhanced dopaminergic input into the primary auditory neuron may inhibit the (over)excitation of this neuron by glutamatergic input from inner hair cells.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

A comparison of three stereotactic radiotherapy techniques; ARCS vs. noncoplanar fixed fields vs. intensity modulation.

PURPOSE: Linac arc based stereotactic radiotherapy is being used with increasing frequency to treat brain tumors. This approach can be used for single or fractionated treatments, and is typically carried out with circular collimators which are optimal for small, spherical targets. Treatment planning using fixed noncoplanar beams or intensity-modulated beams may enhance the ability to conform to irregularly shaped and/or large tumors, especially when combined with stereotactic localization. We compare the dose conformity and normal brain dose characteristics of three stereotactic techniques for various nonspherical target shapes. METHODS AND MATERIALS: Three intracranial test targets were constructed using a 3D treatment planning system after a patient underwent CT simulation. The targets included an ellipsoid with major axis dimensions of 4.0, 2.0, and 2.0 cm, a hemisphere with a diameter of 4.0 cm, and an irregularly shaped patient tumor with a maximum dimension of 5.3 cm. The following stereotactic techniques were compared for each target: a) 5 arcs as used in traditional linac radiosurgery/radiotherapy (noncoplanar arcs [ARCS]), b) 6 fixed noncoplanar custom blocked fields (3D), c) intensity modulation using 6 noncoplanar beams and a mini-multileaf collimator (intensity-modulated radiation therapy [IMRTI). Dose volume histograms were performed for each target/technique combination. RESULTS: For the ellipsoid, dose conformity is similar for all three techniques and normal brain isodose distributions are more favorable with the ARCS plan. For the hemisphere and irregular tumor targets, dose conformity and high/low isodose normal brain volumes are more favorable with the IMRT technique. CONCLUSIONS: For the targets described above, the intensity-modulated technique results in improved dose conformity and decreased dose to nontarget brain in high and low isodose regions as compared to the standard noncoplanar arc technique or noncoplanar fixed fields for the hemisphere and tumor targets. Intensity-modulated treatment delivery may allow for an increase in the therapeutic ratio for treating stereotactically defined large and/or irregularly shaped intracranial targets.

Brain Neoplasms↗
PubMed1999

Intensity-modulated tangential beam irradiation of the intact breast.

PURPOSE: To evaluate the potential benefits of intensity modulated tangential beams in the irradiation of the intact breast. METHODS AND MATERIALS: Three-dimensional treatment planning was performed on five left and five right breasts using standard wedged and intensity modulated (IM) tangential beams. Optimal beam parameters were chosen using beams-eye-view display. For the standard plans, the optimal wedge angles were chosen based on dose distributions in the central plane calculated without inhomogeneity corrections, according to our standard protocol. Intensity-modulated plans were generated using an inverse planning algorithm and a standard set of target and critical structure optimization criteria. Plans were compared using multiple dose distributions and dose volume histograms for the planning target volume (PTV), ipsilateral lung, coronary arteries, and contralateral breast. RESULTS: Significant improvements in the doses to critical structures were achieved using intensity modulation. Compared with a standard-wedged plan prescribed to 46 Gy, the dose from the IM plan encompassing 20% of the coronary artery region decreased by 25% (from 36 to 27 Gy) for patients treated to the left breast; the mean dose to the contralateral breast decreased by 42% (from 1.2 to 0.7 Gy); the ipsilateral lung volume receiving more than 46 Gy decreased by 30% (from 10% to 7%); the volume of surrounding soft tissue receiving more than 46 Gy decreased by 31% (from 48% to 33%). Dose homogeneity within the target volume improved greatest in the superior and inferior regions of the breast (approximately 8%), although some decrease in the medial and lateral high-dose regions (approximately 4%) was also observed. CONCLUSION: Intensity modulation with a standard tangential beam arrangement significantly reduces the dose to the coronary arteries, ipsilateral lung, contralateral breast, and surrounding soft tissues. Improvements in dose homogeneity throughout the target volume can also be achieved, particularly in the superior and inferior regions of the breast. It remains to be seen whether the dosimetric improvements achievable with IMRT will lead to significant clinical outcome improvements.

Breast↗
PubMed1999

Centripetal modules and ancient introns.

We have created an algorithm which instantiates the centripetal definition of modules, compact regions of protein structure, as introduced by Go and Nosaka (M. Go and M. Nosaka, 1987. Protein architecture and the origin of introns. Cold Spring Harbor Symp. Quant. Bio. 52, 915-924). That definition seeks the minima of a function that sums the squares of C-alpha carbon distances over a window around each amino acid residue in a three-dimensional protein structure and identifies such minima with module boundaries. We analyze a set of 44 ancient conserved proteins, with known three-dimensional structures, which have intronless homologues in bacteria and intron-containing homologues in the eukaryotes, with a corresponding set of 988 intron positions. We show that the phase zero intron positions are significantly correlated with the module boundaries (p = 0.0002), while the intron positions that lie within codons, in phase one and phase two, are not correlated with these 'centripetal' module boundaries. Furthermore, we analyze the phylogenetic distribution of intron positions and identify a subset of putatively 'ancient' intron positions: phase zero positions in one phylogenetic kingdom which have an associated intron either in an identical position or within three codons in another phylogenetic kingdom (a notion of intron sliding). This subset of 120 'ancient' introns lies closer to the module boundaries than does the full set of phase zero introns with high significance, a p-value of 0.008. We conclude that the behavior of this set of introns supports the prediction of a mixed theory: that some introns are very old and were used for exon shuffling in the progenote, while many introns have been lost and added since.

Algorithms↗
PubMed1997

Flagellin, a major protein present in SDS-PAGE profiles of Sarkosyl-OMP-enriched fractions from Bordetella bronchiseptica Bvg- or modulated Bvg+ strains.

The bvg or vir locus positively regulates the expression of many Bordetella virulence-associated determinants (encoded by vag genes), including cell envelope proteins, in response to environmental stimuli. On the other hand, several genes named vrg genes are negatively controlled by the bvg regulon (Knapp and Mekalanos, 1988). Flagellin is encoded by a vrg gene, which is expressed when the principal virulence factors are eliminated during antigenic modulation or in phase variants (Akerley et al., 1992). We have previously analyzed SDS-PAGE profiles of Sarkosyl-outer membrane protein (OMP)-enriched fractions from B. bronchiseptica Bvg- and modulated Bvg+ strains and reported a major band associated with the avirulent phenotype (Passerini de Rossi et al., 1995). In order to characterize this band we have purified flagellar filaments from Bvg- and modulated Bvg+ strains, and analyzed them by SDS-PAGE. These profiles revealed a single major band of 40 or 45 kDa depending on the strain. The N-terminal amino acid sequence of the putative flagellin expressed by BB7200a was identical over the first 21 residues analyzed to that of the flagellin from the modulated strain BB7865 reported by Akerley et al. (1992). Comparison of the SDS-PAGE profile of flagellar filaments with that of the OMP-enriched fraction of the corresponding strain showed that the flagellum-associated polypeptide had the same electrophoretic mobility as that of the characteristic band of the avirulent phenotype. Furthermore, this band was absent in the OMP-enriched fraction profile from a Bvg- strain subjected to a treatment that removes flagella. Our results indicate that the major protein observed in SDS-PAGE profiles of Sarkosyl-OMP-enriched fractions from B. bronchiseptica Bvg- and modulated Bvg+ strains corresponds to flagellin.

Amino Acid Sequence↗
PubMed1998

Ion channel modulation as the basis for general anesthesia.

(1) Modulation of the function of the GABA(A) and neuronal nicotinic acetylcholine receptor channels caused by general anesthetics and modulation of the GABA(A) receptor-channel by halothane, enflurane, isoflurane, and n-octanol was channel state-dependent. (3) Halothane modulation of the GABA(A) receptor was independent of subunits, but n-octanol modulation was subunit-dependent. (4) Ethanol at 30-100 microM was very potent in accelerating the desensitization of currents induced by acetylcholine. (5) The ethanol modulation was subunit- and state-dependent, occurring in the alpha3beta4 combination but only weakly in the alpha3beta2 combination. (6) In contrast, halothane at 430 microM (approximately 1 MAC) potently suppressed ACh-induced currents in the alpha3beta2 subunit combination.

Anesthesia, General↗
PubMed2001

Responses of young and aged rat inferior colliculus neurons to sinusoidally amplitude modulated stimuli.

The inferior colliculus (IC) is a processing center for monaural and binaural auditory signals. Many units in the central nucleus of the inferior colliculus (CIC) respond to amplitude and frequency modulated tones, features found in communication signals. The present study examined potential effects of age on responses to sinusoidally amplitude modulated (SAM) tones in CIC and external cortex of the inferior colliculus (ECIC) units in young and aged F344 rats. Extracellular recordings from 154 localized single units of aged (24 month) rats were compared to recordings from 135 IC units from young adult (3 month) animals. SAM tones were presented at 30 dB above threshold. Comparisons were made between CIC and ECIC regarding the percentage of units responding to SAM stimuli, the relationship between SAM responsiveness and temporal response patterns, maximum discharge rates and maximum modulation gains, shapes of rate transfer functions and synchronization modulation transfer functions (MTFs) in response to SAM tones. Sixty percent of units in young and aged rat IC were selectively responsive to SAM stimuli. Eighty-one percent of units classified as onset temporal response patterns were not tonically responsive to SAM stimuli. Median maximum discharge rate in response to SAM tones was 17.6/s in young F344 rats; median maximum modulation gain was 3.85 dB. These measurements did not change significantly with age. Thirty-seven percent of young rat units displayed bandpass MTFs and 53% had lowpass MTFs. There was a significant age-related shift in the distribution of MTF shapes in both the CIC and ECIC. Aged animals showed a lower percentage of bandpass functions and a higher percentage of lowpass functions. Age-related changes observed in SAM coding may reflect an altered balance between excitatory/inhibitory neurotransmitter efficacy in the aged rat IC, and/or possibly a change in the functional dynamic range of IC neurons.

Acoustic Stimulation↗
PubMed2002

Addition of noise enhances neural synchrony to amplitude-modulated sounds in the frog's midbrain.

The ability of 109 single units in the midbrain acoustic centre of frogs (Rana ridibunda, Rana temporaria) to reproduce 10%, 20 Hz sinusoidal amplitude modulation of a long-duration characteristic frequency tone was studied. The sinusoidal modulation was presented either in isolation or summed with a low-frequency (0-50 Hz) noise. Recordings were obtained in the adapted state. The magnitude of the 20 Hz periodic response component was estimated by means of the synchronisation coefficient and the amplitude of the sine modulation of the instantaneous spike rate. In many units, addition of noise modulation produced considerable enhancement of both the mean discharge rate and the discharge rate synchronised to the 20 Hz amplitude modulation. This enhancement phenomenon is interpreted in the context of stochastic resonance theory.

Acoustic Stimulation↗
PubMed1998

Processing of sinusoidally frequency modulated signals in the nuclei of the lateral lemniscus of the big brown bat, Eptesicus fuscus.

Neurons in the nuclei of the lateral lemniscus (NLL) of the big brown bat, Eptesicus fuscus, show several distinctive patterns of response to unmodulated tones. Previous work suggests that sustained responders are specialized to transmit information about sound level and duration while onset responders transmit precise timing information. The biosonar signals of E. fuscus consist of multiple, downward frequency modulated sweeps that change in slope and repetition rate as the bat approaches a target. An obvious hypothesis would be that NLL neurons with sustained responses should discharge during the time when the frequency of a signal is within their response area, but that onset responders should discharge each time the frequency enters the excitatory portion of their response area. In this study we examined the responses of NLL neurons to sinusoidally frequency modulated (SFM) signals presented monaurally to awake, restrained bats. Extracellular recordings were obtained from single neurons in the multipolar and columnar divisions of the ventral nucleus (VNLLm and VNLLc), the intermediate nucleus (INLL) and the dorsal nucleus of the lateral lemniscus (DNLL). All NLL neurons responded synchronously to SFM signals under some conditions. The temporal precision of synchronization was quantified using a coefficient of synchronization (CS), where a value of I equals perfect synchrony. Maximum CS values ranged from 0.70 to >0.99, were generally highest at low modulation rates ( <200 Hz), and showed lowpass characteristics for modulation rate. The maximal modulation rates that elicited synchronous discharge ranged from 50 to 500 Hz. The highest maximal rates were found in the VNLLm and VNLLc, the lowest in DNLL. The ability of NLL neurons to synchronize their discharge to the pattern of an SFM signal is intermediate between that of neurons in the cochlear nucleus and in the inferior colliculus. For the majority of neurons in VNLLm, INLL and DNLL, the precision of synchronization was approximately equal for the downward and upward components of the SFM signal; in contrast, 69% of VNLLc neurons responded selectively to the downward component of the SFM signal. All VNLLc neurons and a subset of those in VNLLm, INLL, and DNLL responded synchronously to SFM signals only if the frequency excursions included a border of the excitatory frequency bandwidth, suggesting that the synchronous discharge was due primarily to the repeated passage of the stimulus frequency into and out of the excitatory portion of the response area. In the case of VNLLc neurons, only the high frequency border was effective; Other neurons, especially those in DNLL, responded synchronously to SFM signals with frequency excursions that were confined entirely within the excitatory response area.

Acoustic Stimulation↗
PubMed1999

Some effects of background noise on modulation detection interference.

Modulation thresholds were obtained for a 2000-Hz signal carrier modulated at a rate of 10 Hz. Thresholds were obtained without a masker carrier and in the presence of a masker carrier that was either unmodulated or modulated at a rate of 10 Hz and a depth of 100% (m(m) = 1.0). Of primary interest was whether the amount of interference caused by the masker was influenced by the frequency proximity of the masker to the signal, and whether background noise had an influence on that proximity effect. In general, for masker carriers higher in frequency than the 2000-Hz signal carrier, there was a tendency for the interference to decline as the masker was moved farther away from the signal for masker carriers lower than 2000 Hz, there was little or no proximity effect. Broadband noise eliminated the proximity effect obtained with an unmodulated masker, but not that obtained with a modulated masker. Results with a narrowband noise suggest that the broadband noise has its effect by masking the high-frequency side of the signal's excitation pattern. These results, as well as the results of an excitation pattern analysis, suggest that the proximity effect with all unmodulated masker may be mediated via a peripheral, within-channel interaction, whereas that with a modulated masker may be mediated via a central, across-channel interaction.

Acoustic Stimulation↗
PubMed2000

Human auditory steady-state responses to amplitude-modulated tones: phase and latency measurements.

Human auditory steady-state responses were recorded to four stimuli, with carrier frequencies (f(c)) of 750, 1500, 3000 and 6000 Hz, presented simultaneously at 60 dB SPL. Each carrier frequency was modulated by a specific modulation frequency (f(m)) of 80.6, 85.5, 90.3 or 95.2 Hz. By using four different recording conditions we obtained responses for all permutations of f(m) and f(c). The phase delays (P) of the responses were unwrapped and converted to latency (L) using the equation: L=P/(360xf(m)). The number of cycles of the stimulus that occurred prior to the recorded response was estimated by analyzing the effect of modulation frequency on the responses. These calculations provided latencies of 20.7, 17.7, 16.1 and 16.1 ms for carrier frequencies 750, 1500, 3000 and 6000 Hz. This latency difference of about 4.5 ms between low and high carrier frequencies remained constant over many different manipulations of the stimuli: faster modulation rates (150-190 Hz), binaural rather than monaural presentation, different intensities, stimuli presented alone or in conjunction with other stimuli, and modulation frequencies that were separated by as little as 0.24 Hz. This frequency-related delay is greater than that measured using transient evoked potentials, most likely because of differences in how transient and steady-state responses are generated and how their latencies are determined.

Acoustic Stimulation↗
PubMed1995

The correction of interarch malocclusions using a fixed force module.

This article describes the use of a flexible force module (the Jasper Jumper) that can be incorporated into existing fixed appliances to correct various types of sagittal malocclusion. Essentially the spring mechanism described in this article is a modification of the original bite jumping mechanism of Herbst. The flexible spring module provides greater freedom of mandibular movement than is possible with the more rigid mechanism of the Herbst appliance. The facial musculature applies force through these modules to the anchor points to produce a variety of treatment effects. The treatment effects produced by the module mimic those previously described for the Herbst appliance and include posterior movement of the maxillary buccal segments and anterior movement of the mandible or mandibular dentition or both. Specifics of the clinical management of this modular system are discussed, including anchorage preparation and torque application, as well as the methods of anchoring, activating and reactivating the modules.

Activator Appliances↗
PubMed2002

Attention modulation of neural tuning through peak and base rate in correlated firing.

The present study investigates the influence of attention modulation on neural tuning functions under a Gaussian correlation structure. Recent experiments have shown that attention modulates the tuning curve via its height and base rate. Inspired by this experimental finding, we previously showed the effective size of attention modulation (i.e. the critical length) on the neural population that enhances encoding accuracy. The previous result, however, was obtained under the assumption of uncorrelated firing, i.e. stimulus-conditional independence of neural responses. A question still remains whether the above findings can be applied to correlated firing. It is important to investigate this issue partly because neural firings are usually correlated but even more so because common attentional inputs may cause correlated firings. The present study first provides the general framework of attention modulation in relation to an attended stimulus and an actual stimulus and then shows the existence of a critical length under a Gaussian correlation structure. In order to improve encoding accuracy, measured by the Fisher information, the height and the base rate should be increased when the attended stimulus is in the critical length from the peak of the tuning curve and decreased otherwise. Furthermore, we confirm that a similar nature of the critical length also holds even when the neural decoder uses an uncorrelated unfaithful model. Thus, the existence of the critical length seems to be a ubiquitous phenomenon in attention modulation, and so its implications are discussed.

Attention↗
PubMed1997

Frequency- and phase-modulated heteronuclear decoupling in rotating solids.

The mechanism of heteronuclear dipolar decoupling by the TPPM sequences, proposed by Bennett et al. (J. Chem. Phys. 103 (1995) 6951) is investigated by comparison with a modified pulse sequence, called TPFM, that uses frequency instead of phase modulation. By combining frequency and phase modulations, circularly modulated sequences are designed. The fact that only the left-handed modulation sequence FMPML leads to improved proton decoupling, while the right-handed modulation sequence FMPMR is ineffective, proves that the efficient decoupling is caused by a secondary resonance effect.

Chemical Phenomena↗
PubMed1993

Type A modules: interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins.

A 200-amino acid long motif first recognized in von Willebrand Factor (type A module) has been found in components of the extracellular matrix, hemostasis, cellular adhesion, and immune defense mechanisms. At present the extracellular matrix is the predominant site of expression of type A modules since at least four non-fibrillar collagens and two non-collagenous proteins contain a variable number of modules ranging from one to twelve. The modules conform to a consensus motif made of short conserved subregions separated by stretches of variable length. The proteins that incorporate type A modules participate in numerous biological events such as cell adhesion, migration, homing, pattern formation, and signal transduction after interaction with a large array of ligands.

Amino Acid Sequence↗
PubMed1999

The effect of arginine-428 mutation on modulation of activity of human liver flavin monooxygenase 3 (FMO3) by imipramine and chlorpromazine.

This study was carried out to investigate the molecular basis for modulation of recombinant FMO3-catalyzed activity by the tricyclic antidepressants, imipramine and chlorpromazine. A mutant of human liver FMO3 (T428R) was formed by site-directed mutagenesis and characterized along with the native enzyme in order to elucidate a possible structure-function relationship. Functional properties of native and T428R human FMO3s were studied with methimazole as substrate. Both enzymes catalyzed the S-oxidation of methimazole with the same Km value. Imipramine modulated the activities of the native and T428R human FMO3s differently; the activity of the native FMO3 was increased at all concentrations, whereas the activity of the mutant enzyme was inhibited at concentrations above 300 microM. Chlorpromazine activated the native enzyme at all concentrations of methimazole but activated the mutant enzyme only at high substrate concentrations. The direction (activation or inhibition) and extend of modulation of FMO3 activity is not only dependent on the concentration of the modulator, it is also dependent on the substrate concentration. This study confirms our previous findings with FMO1 that position 428 is important in the interaction of the FMO with modulators.

Arginine↗
PubMed2000

Structure and function of laminin LG modules.

Laminin G domain-like (LG) modules of approximately 180-200 residues are found in a number of extracellular and receptor proteins and often are present in tandem arrays. LG modules are implicated in interactions with cellular receptors (integrins, alpha-dystroglycan), sulfated carbohydrates and other extracellular ligands. The recently determined crystal structures of LG modules of the laminin alpha2 chain reveal a compact beta sandwich fold and identify a novel calcium binding site. Binding epitopes for heparin, sulfatides and alpha-dystroglycan have been mapped by site-directed mutagenesis and show considerable overlap. The epitopes are located in surface loops around the calcium site, which in other proteins (agrin, neurexins) are modified by alternative splicing. Efficient ligand binding often requires LG modules to be present in tandem. The close proximity of the N- and C-termini in the LG module, as well as a unique link region between laminin LG3 and LG4, impose certain constraints on the arrangement of LG tandems. Further modifications may be introduced by proteolytic processing of laminin G domains, which is known to occur in the alpha2, alpha3 and alpha4 chains.

Amino Acid Sequence↗
PubMed1996

Structure and function of fibronectin modules.

Fibronectin is an important component of the extracellular matrix and is involved in a diverse range of physiological processes. It is a mosaic protein composed almost entirely of three types of module, F1, F2 and F3. Although the structures of single F1, F2 and F3 modules have been available for a number of years, in many cases the key to understanding the structure-function relationships in fibronectin and other proteins containing these modules lies in studies of module pairs and larger domains. This review focuses on recent advances in the understanding of the structure and function of fibronectin modules.

Amino Acid Sequence↗