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A Dancer

Publications and source records attributed to A Dancer.

17 recordsLinked to original sources

Expression of thymidine kinase driven by an endothelial-specific promoter inhibits tumor growth of Lewis lung carcinoma cells in transgenic mice.

The possibility of inhibiting tumor growth by limiting angiogenesis has raised considerable interest. In this study, we examined the feasibility of inhibiting tumor growth by targeting a suicide gene in the endothelium. Toxicity must be directed solely to angiogenic cells. Therefore, we used the herpes simplex virus-thymidine kinase (TK) gene, in combination with the prodrug ganciclovir (GCV), which affects replicative cells. To test this strategy, we produced transgenic mice carrying the TK gene driven by the vascular endothelial (VE)-cadherin promoter. Lewis lung carcinoma cells were injected subcutaneously to establish tumors and to test the effect of GCV on tumor growth. In two independent transgenic lines, GCV treatment (75 mg/kg/day) resulted in a 66-71% reduction of tumor volume at day 20 postimplantation compared to wild-type mice (650 and 550 versus 1930 mm(3), P<0.02 and 0.01, respectively), whereas no significant difference was observed when vehicle alone was injected. Tumor growth inhibition was accompanied by a marked reduction in tumor vascular density (151 versus 276 vessels/mm(2), P<0.05) and an increase in tumor cell death, suggesting that tumor growth inhibition was caused by a reduction in tumor angiogenesis. Our data support the potential utility of endothelial targeting of suicide genes in cancer therapy.

Animals↗

Treatment of acoustic trauma.

The aim of this study is to determine the actual efficiency of the present medical treatments of acoustic trauma. Untreated and treated groups of guinea pigs are exposed to a traumatic noise exposure, inducing up to 60-dB threshold shift. The recovery is followed for up to 14 days. The first results indicate that in some animals the recovery of the threshold shifts are complete despite the fact that significant areas of hair cells are damaged. The most widely used medical treatments of acoustic trauma (oxygenotherapy, carbogen, hyperbaric oxygen, vasoactive agents, and corticotherapy) have been tested. Preliminary results indicate that pure oxygen and carbogen seem ineffective, hyperbaric oxygen used alone is dangerous, and corticoids and combined corticoid/hyperbaric oxygen seem to improve functional and morphological recovery. This study will be taken as a reference to look for new treatments that will be applied directly to the cochlea by means of an implanted osmotic micropump.

Action Potentials↗

Direct evidence of cubic difference tone propagation by intracochlear acoustic pressure measurements in the guinea-pig.

The fine tuning mechanisms involved in the normal processing of sound in the cochlea are non-linear, hence combination tones are generated inside the cochlea when a pair of low-level pure tones with neighbouring frequencies f1 and f2 is used as a stimulus. Their detection as sounds in the ear canal proves that they undergo backward propagation in the cochlea and through the middle ear, and the non-invasive measurement of the combination tone at 2f1-f2, called the cubic difference tone (CDT), has become a routine method of monitoring cochlear function. In order to gain information on the hypothetical places where CDTs are generated, on their intracochlear levels and propagation velocities, direct measurements of CDT pressure waves were carried out in scala vestibuli and tympani of the first and second turn of the guinea-pig cochlea. Cubic difference tones at 2f1-f2 varied from 0.75 to 9 kHz and were measured with a miniature piezoresistive transducer. Its high sensitivity allowed the detection of CDTs whenever their levels exceeded 5 dB SPL in the ear canal, i.e. 40 dB SPL (re: 20 microPa) inside the cochlea. The levels of CDTs were similar in scala vestibuli of the first and second turn. Phase comparisons between measurements at 2f1-f2 in the first and second turn allowed determination of the place where the CDT phase was minimum. It provided an estimation of the generation site of the CDT, which appeared to be close to the place tuned to f2 for stimulus levels lower than 70 dB SPL. Forward and backward travel times from one turn to the other were assessed at several frequencies, and both values were shorter than 0.2 ms. In contrast, the overall 'round-trip' delay of CDTs, measured in the ear canal, was about five times larger, suggesting that local filtering processes rather than propagation delays account for the overall CDT delay.

Acoustic Stimulation↗

The specific problems of noise in military life.

In military life, noise has unusual characteristics and constitutes a serious hazard for hearing. Hearing impairments due to the exposure to weapon noises represent an important prejudice for the health of many soldiers. A special attention is given to (i) the "critical level", (ii) the frequency localization of the threshold shifts, (iii) the actual influence of the protective reflexes of the ear, (iv) the existence of delayed threshold shifts following impulse noise exposures, and (v) the interest of the medical treatment of the acoustic trauma. Damage risk criteria for weapon noises are compared: criteria using the (A-weighted) isoenergy principle represent the best present solution (LAeq = 85 dB). Specific problems related to the use of hearing protection are also discussed.

Auditory Threshold↗

Reverse middle-ear transfer function in the guinea pig measured with cubic difference tones.

Otoacoustic emissions are increasingly useful for determining cochlear function noninvasively. It is widely agreed that these acoustic signals reflect micromechanical processes in the cochlea. However, their quantitative interpretation requires knowledge of the ways in which vibrations travelling back to the ear canal from the cochlea are shaped by the middle ear. An intracochlear source is needed to derive the reverse middle-ear transfer function (rMETF) by comparing pressure in the external ear canal to the corresponding pressure in scala vestibuli. In the present study, the rMETF was obtained in vivo in the guinea pig using as intracochlear sound source the cubic difference tones (CDTs) generated by a pair of external pure tones. With a closed ear canal and open bulla, the rMETF was found to be flat (-35 dB) over a broad frequency range (1.5-8 kHz). The differences between forward and reverse METF could be explained by different loads acting on the middle ear network, which depends on the direction of signal transmission. With knowledge of the rMETF, it becomes possible to quantify CDTs within the cochlea by measuring them noninvasively in the ear canal.

Acoustic Stimulation↗

[Biomechanics of the middle ear].

We describe the main biomechanical characteristics of the middle ear in man and in animals. Physical principles of functionment, tympano-ossicular displacements, acoustic reflex, adaptation of impedance, transfer function of the middle ear, middle ear as an acoustic power transformer... are presented. Practical consequences for the hearing sensitivity, the susceptibility to noise and some clinical applications are discussed.

Acoustics↗

[Effect of noise on the auditory transduction].

The effects of noise on the auditory transduction and the temporary and permanent threshold shifts (TTS and PTS) are reviewed in relation to the physiology, the morphology and the mechanics of the Corti's organ and especially of the outer hair cells. The modification of the mechanical characteristics of the stereocilia: decrease of stiffness, shortening of the rootlets, softening of the interciliary links...reduce the number of ionic channels which are opened during the mechanical excitation of the Corti's organ. This reduction modifies greatly the behavior of the "cochlear amplifier" which is located at the level of the outer hair cells and is responsible for the auditory sensitivity at threshold and the frequency selectivity. Permanent damages to the stereocilia of the hair cells following exposure to noise seem to be the main factor responsible for the apparition and the extent of the hearing losses. The influence cof several parameters: amplitude, duration, frequency..., on TTS and PTS are reviewed and the phenomenon of the half-octave shift is described.

Auditory Pathways↗

Effectiveness of earplugs in high-intensity impulse noise.

The efficiency of different types of earplugs was assessed by means of Békésy audiometry following the exposure of 42 human subjects to weapon impulses. The peak pressure of the impulses ranged from 2.3-27.8 kPa (from 161 to 183-dB peak SPL) and the A-weighted equivalent level (over 8 h) of each exposure ranged from 100-114 dB. All subjects wore earplugs fitted by an experienced individual. The devices tested included one brand of conventional foam earplugs and a number of different models of perforated earplugs, one type of which had been previously shown to provide nonlinear attenuation. Perforated earplugs were tested because they provide better speech communication than conventional passive earplugs, and in the nonlinear case also afford attenuation that increases with the peak pressure of the impulses. The temporary threshold shifts (TTSs) observed in these experiments were very small and indicated no significant hazard for hearing. Well-fitted perforated earplugs seem to be able to protect the ear from infrequent exposures to the high-level impulses produced by small and large weapons while allowing good speech communication, and without impairing the operational capacity of soldiers who must remain aware of their acoustic environment.

Adult↗

Experimental look at cochlear mechanics.

The mechanisms by which the organ of Corti is stimulated by acoustic stimuli are discussed on the basis of experimental observations. This discussion refers to the resonance theory as well as to the traveling wave (TW) theory. The measurement of the basilar membrane displacements, of the cochlear microphonic (CM) responses to pure tones and impulses, and the recording of the intracochlear acoustic pressure seem to indicate that, at least in the basal part of the cochlea and for frequencies up to the characteristic frequency of a given location, the cochlear responses do not exhibit large phase lags and long delays which characterize the one-dimensional long-wave models (in which a TW transports the energy along the cochlear partition). These experimental observations suggest that the cochlear partition is excited simultaneously as a whole, more or less like a bank of resonators, as proposed a long time ago by Helmholtz.

Acoustic Stimulation↗

Delayed temporary threshold shift induced by impulse noises (weapon noises) in men.

Most of the available information on the effects of impulse noise on hearing is derived from temporary threshold shift (TTS2) measurements performed 2 min after a single exposure to small-weapon noises. TTS is known to recover as a linear function of the logarithm of time when it is induced by a continuous noise of moderate intensity. Following the exposure to impulse noise, several investigators have reported individual exceptions to the log-time relation, e.g. increases in TTS during the first hour of recovery. These authors observed a 'rebound recovery function' for most of the exposed men, and they conclude that this phenomenon '... has implications for the use of TTS in the construction of damage risk criteria for hazardous noise exposure ..., a single measure, such as the widely used TTS2 may not be an adequate index of the magnitude of the TTS'. In order to thoroughly investigate in man the existence of 'delayed' TTS following the exposure to actual weapon noises, the 'French Committee on Weapon Noises' carried out the following study. Three groups of soldiers (28 subjects) wearing no hearing protection were exposed in the free field over 2 days to impulse noises produced by a rifle. Békésy audiograms were obtained from each subject just before the exposure, and at 5 min, 1 h and 4 h after exposure. All audiometric tests were carried out even when no TTS was observable in the first postexposure audiogram. A significant number of subjects showed a 'delayed TTS' and/or 'rebound recovery'. The maximum TTS was observed at 1 h after exposure, but the observation of a delayed recovery and a rebound recovery indicate that audiometric tests should be performed in all cases at least up to 4 h after the exposure. More detailed work is necessary to establish what changes may be necessary in the present damage risk criteria for impulse noises of a very high level.

Adult↗

Effect of the temporal pattern of a given noise dose on TTS in guinea pigs.

To show the effect of the temporal pattern of acoustic stimulation on TTS 15 min, guinea pigs were subjected to isoenergetic noises with the same spectrum. The exposures in a first experimental series were continuous noises and noise bursts. The continuous noise was presented with different durations and levels but always with the same energy. The noise burst stimulation consisted of a constant number of bursts with different interstimulus intervals. Both duration and repetition rate were shown to affect the TTS 15 min measured for these isoenergetic stimuli. A duration of 225 to 1800 s and a repetition rate of one per second produced the greatest TTS 15 min. In a second experimental series continuous noise and acoustic impulses with the same spectrum and 100-Hz repetition rate were presented at different levels. In this case the waveform of the stimulus (phase spectrum) was shown to have an effect on TTS 15 min.

Acoustic Stimulation↗

Cochlear mechanisms at low frequencies in the guinea pig.

The study of the cochlear microphonic and of the intracochlear sound pressure in guinea pigs shows that the behavior of the cochlea at very low frequencies is controlled by three discrete elements: (a) the compliance of the whole basilar membrane; (b) the acoustic resistance of the helicotrema; (c) the compliance of the round window. The part of each of these elements has been established. The compliance of the whole basilar membrane produces constant amplitudes at frequencies lower than the minimum frequency at which a travelling wave is present (130 Hz). In fact, this constant amplitude range is limited by connection of the two cochlear scalae through the helicotrema resistance. This protecting mechanism produces an attenuation slope for frequencies lower than 80 Hz. The compliance of the round window does not modify the slope of the cochlear microphonic, but it induces a constant sound pressure in scala tympani up to 200 Hz. Decreasing of the sound pressure in the scala vestibuli is, therefore, limited for frequencies less than 30 Hz by this constant value of the sound pressure in scala tympani.

Acoustic Stimulation↗

Intracochlear sound pressure measurements in guinea pigs.

The intracochlear sound pressure in guinea pigs was measured in the scala vestibuli of the first, second and third turns as well as in the scala tympani of the first and second turns. The acoustic stimuli were pure tones delivered over the frequency range 30--20 000 Hz at sound levels ranging from 60 to 100 dB. The results achieved show the sound pressure in scala vestibuli to be practically in phase in the first three turns. In scala tympani the pressure varies within wide limits when passing from the first to the second turn, but it is equal to the pressure in scala vestibuli at frequencies in excess of the best frequency of the point considered. The difference in instantaneous pressure acting on the basilar membrane exhibits the characteristics of a traveling wave. This pressure difference corresponds to the displacement of the basilar membrane evaluated from recordings of the microphonic potential.

Basilar Membrane↗

Intracochlear acoustic pressure measurements: transfer functions of the middle ear and cochlear mechanics.

Direct intracochlear acoustic pressure recordings (from 20 to 20,000 Hz) are used to measure the middle-ear transfer functions (forward and reverse) and to better understand the cochlear mechanics in the guinea pig. In the forward direction, the middle-ear transfer function is strongly dependent on the frequency and presents a maximum of +30 dB at 1,000 Hz (bulla open). In the reverse direction, the middle-ear transfer function looks like an ideal reverse middle-ear pressure transformer with -35 dB gain and 0 degrees phase lag from 20 to 8,000 Hz (bulla open, closed ear canal). Passive cochlear mechanics is studied with the help of intracochlear pressure measurements and differential cochlear microphonic potential recordings in the different turns.

Acoustic Stimulation↗