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I J Russell

Publications and source records attributed to I J Russell.

At least 55 records · Page 3Linked to original sources
PubMed1994

Transfer characteristic of the inner hair cell synapse: steady-state analysis.

Inner hair cells (IHC) transduce mechanical to electrical energy in the mammalian cochlea producing a receptor potential which is a rectified, filtered representation of the mechanical input to the hair cell. The IHC synapse transfers the information in the receptor potential to the fibers of the auditory nerve (whose cell bodies form the spiral ganglion) where it is encoded as a pattern of action potentials. That transfer was investigated by comparing the steady-state responses in pre- and post-synaptic cells. A nonlinear transfer characteristic describing the synapse was generated by plotting the spiral ganglion cell firing rate as a function of the IHC receptor potential. For each spiral ganglion unit, the operating range maps onto a different portion of the nonlinear inner hair cell operating range, dependent on the neural unit's threshold. Units whose rate-level functions exhibit similar slopes but different thresholds can have dramatically differing sensitivities to changes in the IHC potential. This threshold-dependent mapping supports the concept that information may be distributed amongst nerve fibers according to their threshold.

Acoustic Stimulation↗
PubMed1992

Nonlinear mechanical responses of mouse cochlear hair bundles.

The stiffness of sensory hair bundles of both inner (IHC) and outer (OHC) hair cells was measured with calibrated silica fibres in mouse cochlear cultures to test the hypothesis that the mechanical properties of the hair bundle reflect processes underlying mechanotransduction. For OHCs, the displacement of the hair bundle relaxed with time constants of 6 ms for displacements which open transducer channels and 4 ms for displacements which close the channels. The corresponding values of the time constants for IHCs were 10 ms and 8 ms, respectively. A displacement-dependent change in the stiffness of the hair bundle was not observed when the bundle was displaced orthogonally to the direction of excitation. The stiffness of the hair bundle as a function of nanometre displacements from the resting position was remarkably nonlinear. The stiffness declined to a minimum from the resting stiffness by about 12% for OHCs and 20% for IHCs when the hair bundle was displaced by about 20 nm in the excitatory direction, and it increased by a similar amount when the bundle was displaced by 20 nm in the inhibitory direction. The displacement at which the stiffness reached a minimum was within the most sensitive region of the hair-cell transducer function (receptor potential as a function of hair-bundle displacement), and the displacement at which the stiffness reached a maximum was at the point of saturation of the transducer function in the inhibitory direction. The nonlinear displacement-dependent compliance change is reversibly abolished, and the time constant of relaxation of the bundle for excitatory displacements is reversibly reduced, when mechanotransduction is blocked by the addition of either neomycin sulphate or cobalt chloride to the solution bathing the hair cells. The displacement-dependent compliance change was not apparently reduced when the receptor potential was attenuated through the substitution of sodium in the bathing solution with a less permeant cation, tetraethylammonium. These findings suggest that the nonlinear mechanical properties of the hair bundle are associated with aspects of the hair-cell mechanotransducer process. The mechanical properties of the hair bundle are discussed in relation to the 'gating-spring' hypothesis of hair-cell transduction.

Animals↗
PubMed1992

Sensory transduction and frequency selectivity in the basal turn of the guinea-pig cochlea.

Receptor potentials recorded from outer hair cells (OHC) and inner hair cells (IHC) in the basal high-frequency turn were compared. The DC component of the IHC receptor potential is maximized to ensure that IHCS can signal a voltage response to high-frequency tones. The OHC DC component is minimized so that OHCS transduce in the most sensitive region of their operating range. The phase and magnitude of OHC receptor potentials were recorded as an indicator of the magnitude and phase of the energy which is fed back to the basilar membrane to provide the basis for the sharp tuning and fine sensitivity of the cochlea to tones. IHC receptor potentials were recorded to assess the net effect of the feedback on the mechanics of the cochlea. It was concluded that OHCS generate feedback which enhances the IHC responses only at the best frequency. At frequencies below CF, IHC DC responses are elicited only when the OHC AC responses begin to saturate.

Acoustic Stimulation↗
PubMed1992

Voltage responses to tones of outer hair cells in the basal turn of the guinea-pig cochlea: significance for electromotility and desensitization.

Voltage responses were recorded from outer hair cells (OHCS) in the basal coil of the guinea-pig cochlea in response to tones at frequencies above the characteristic frequency (CF) presented together with a 100 Hz tone at 80 dB or 85 dB sound pressure level (SPL). The amplitude and polarity of voltage responses to a 100 Hz, 85 dB SPL tone were altered when presented together with tones at frequencies above CF according to the frequency and level of the high-frequency tone, OHC phasic (ac) (greater than 500 microV) but not tonic (dc) voltage responses were elicited by the high-frequency tone. Thus the responses of OHCS to low-frequency tones can be altered when presented together with a high-frequency tone without an apparent dc change in membrane potential. Recordings were made from an OHC during cochlear desensitization through exposure to an intense tone. The maximum voltage response to high-level low-frequency tones remained unchanged, although the OHC response to high-frequency tones became less sensitive to low-level stimuli and more linear as a function of level. It is suggested that desensitization is associated with a change in the mechanical properties of the cochlea, possibly associated with the OHCS themselves, and not with inactivation of the transducer channels. The amplitude of the OHC ac voltage response was measured at neural threshold, and the consequences of these measurements on hair cell electromotility are considered.

Acoustic Stimulation↗
PubMed1992

Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis.

OBJECTIVE: To compare the levels of biogenic amines in the cerebrospinal fluid (CSF) of primary fibromyalgia syndrome (PFS) patients with those in the CSF of controls. METHODS: Metabolites of serotonin, norepinephrine, and dopamine were identified in CSF, using high performance liquid chromatography with coulometric detection. RESULTS: CSF levels of metabolites from all 3 neurotransmitters were lower in PFS patients than in controls. CONCLUSION: A low rate of turnover of several neurotransmitters supports the proposed hypothesis of a metabolic defect in PFS and suggests that the defect occurs at a neuroregulatory level.

Adult↗
PubMed1992

A cell surface-associated centrosomal layer of microtubule-organizing material in the inner pillar cell of the mouse cochlea.

This investigation provides evidence that pericentriolar material is divorced from the immediate vicinities of centrioles and becomes functionally associated with the plasmalemma during the differentiation of a mammalian cell type. Such events occur prior to the assembly of large transcellular microtubule bundles in columnar epithelial cells called inner pillar cells in the mouse organ of Corti. The microtubules do not radiate from a typical centrosome and its centrioles. They elongate from a microtubule-organizing centre (MTOC), which is deployed as a subapical cell surface-associated layer in each cell. Most of the dense material of this layer, and the tops of most of the microtubules, are initially concentrated around the sides of a cell about 1 microns below its apical surface. In addition, a pair of centrioles is located above the layer, which acts as if it is a pericellular concentration of the pericentriolar material of a modified centrosome. Although microtubule nucleation takes place in a centrosome-like region, 13 protofilament fidelity is not exercised. Most of the microtubules have 15 protofilaments. Microtubule assembly progresses in these cells after the organ of Corti has been isolated for in vitro culture. However, large numbers of microtubules elongate from pericentriolar material juxtaposed against the centrioles. Hence, there is some reversion by the centrosomes of cultured cells to the operational configuration regarded as typical for animal tissue cells in general.

Animals↗
PubMed1992

Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome.

The density of serotonin reuptake receptors on peripheral platelets from 22 patients with primary fibromyalgia syndrome (FS) and the serum serotonin concentrations in 9 patients with FS were compared with those of matched healthy controls. The mean serum serotonin concentration was lower (p = 0.01) in FS than in controls, while the binding of 3H-imipramine was higher (p = 0.035) and normalized with treatment using a combination of ibuprofen and alprazolam. Improvement in selected clinical measures of FS disease activity during treatment correlated with the change in platelet 3H-imipramine binding. These findings support the proposed hypothesis of aberrant pain perception in FS resulting from a deficiency of serotonin.

Blood Platelets↗
PubMed1992

The fibromyalgia and myofascial pain syndromes: a preliminary study of tender points and trigger points in persons with fibromyalgia, myofascial pain syndrome and no disease.

Four experts on myofascial pain syndrome (MFP) performed trigger point examinations and 4 experts on fibromyalgia performed tender point examinations on 3 groups of subjects (7 patients with fibromyalgia, 8 with MFP, and 8 healthy persons) while blinded as to diagnosis. Local tenderness was common in both disease groups (65-82%), but was elicited in a greater proportion of MFP experts' examinations (82%). Active trigger points were found in about 18% of examinations of patients with fibromyalgia and MFP, but latent trigger points were rare in all groups. A more liberal definition of trigger point, however, resulted in a 38 and 23% positive rate among patients with fibromyalgia and MFP, respectively. Taut muscle bands and muscle twitches were common (50 and 30%, respectively) and noted equally in all 3 diagnostic groups. Problems with reliability were identified for taut bands, muscle twitch, and active trigger points. Our data are exploratory and tentative, but suggest that attention to definition and reliability are required to advance our knowledge of these common syndromes.

Fibromyalgia↗
PubMed1992

The phase and magnitude of hair cell receptor potentials and frequency tuning in the guinea pig cochlea.

Voltage responses to tones were recorded intracellularly from inner (IHC) and outer (OHC) hair cells in the basal turn of the guinea pig cochlea. Tone-evoked voltage responses were also recorded extracellularly from fluid-filled spaces adjacent to the hair cells and from supporting cells. The AC component of the OHC voltage responses to tones at frequencies between 8 and 24 kHz and those recorded extracellularly were remarkably similar with respect to phase as a function of sound level, but the magnitude of the AC response was 2-10 times larger when recorded intracellularly from an OHC. At frequencies more than half an octave below the characteristic frequency (CF), the phase of OHC AC response was independent of level, and the slope of the magnitude/level functions was 1 dB/db. At levels exceeding about 70 dB SPL, the slopes became less steep and depolarizing IHC and OHC DC responses appeared. At frequencies one-half an octave below CF and at frequencies between one-third and one-half an octave above CF, notches were present in the AC/level function between 70-100 dB SPL that were accompanied by a sudden phase lag of -180 degrees. These frequency- and level-dependent characteristics were also present in relatively insensitive preparations and were attributed to a change in the phase of OHC excitation due to level-dependent changes in the relative stiffness of the mechanical components of the cochlear partition. At CF the detection thresholds of the OHC AC response and IHC DC response and slopes of the response/level functions were similar. At sound levels around 60 dB SPL, the AC signal began to phase lead, amounting to approximately 90 degrees at 70 dB SPL. Within the same range of levels, the OHC DC potentials first appeared and the IHC DC response began to saturate. At frequencies just above the CF, the phase of the AC component increased with level to a lead of about 180 degrees. OHC and IHC tuning curves are comparable in the tip region, but they differ in that the low- and high-frequency shoulders of the OHC AC tuning curves are more sensitive by 10-30 dB SPL. On the basis of the frequency- and level-dependent characteristics of the IHC and OHC responses, it is proposed that OHC AC potentials provide a measure of the phase and magnitude of the proposed electromechanical feedback of the cochlear partition that enhance frequency tuning in the cochlea.

Acoustic Stimulation↗
PubMed1992

Modulation of hair cell voltage responses to tones by low-frequency biasing of the basilar membrane in the guinea pig cochlea.

Inner (IHC) and outer (OHC) hair cell receptor potentials were recorded during stimulation with combinations of high-frequency (HF) tones and a 100 Hz tone burst of constant level (80 dB SPL). For frequencies at and below characteristic frequency (CF), OHC AC receptor potentials were suppressed by the 100 Hz tone at levels of the HF tone below about 70 dB SPL (the initial steep part of the AC/level function) and at levels that were frequency specific for frequencies above CF. Suppression was associated with a phase lead for frequencies at and close to the CF. For frequencies above CF, the OHC AC response was either suppressed or augmented at levels of the HF tone both below and above 70 dB SPL, depending on the frequency. The action of the 100 Hz tone on the AC response/level functions was to change nonmonotonic functions into monotonic functions or vice versa. IHC DC receptor potentials were suppressed maximally at the CF and at levels and frequencies where suppression of the OHC AC response and the appearance of the IHC DC response overlapped. For levels of the HF tone above 70 dB SPL, the amplitude of the responses of both IHCs and OHCs to the 100 Hz tone are suppressed and become more symmetrical through selective attenuation of the depolarizing phase of the IHC response and the hyperpolarizing phase of the OHC response. In IHCs from insensitive preparations, the response to the 100 Hz tone is augmented in the presence of the HF tone, which may indicate a shift in the operating point of transduction. At frequencies about one-half an octave below the CF, the phase of the 100 Hz voltage response of OHCs but not IHCs is inverted for levels of the HF tone above about 90 dB SPL. It is proposed that amplitude and phase changes in the response to the HF tone due to the presence of the 100 Hz tone are the result of changes in OHC feedback processes and in the mode of movement of the interface between OHC stereocilia and tectorial membrane. The interaction between the responses to HF and 100 Hz tones indicates that feedback contributes significantly to the voltage responses of OHCs throughout the frequency response range.

Acoustic Stimulation↗
PubMed1991

Treatment of primary fibrositis/fibromyalgia syndrome with ibuprofen and alprazolam. A double-blind, placebo-controlled study.

A multidimensional evaluation of 78 patients with primary fibrositis/fibromyalgia syndrome (PFS) revealed no significant relationship between clinical measures of physical discomfort and psychological measures. This observation provided evidence against the notion that the pain of PFS has a psychological etiology. The same patients were randomized into 4 groups for treatment with ibuprofen and/or alprazolam in a randomized, double-blind, double-dummy, placebo-controlled pilot trial. Clinical improvement in patient rating of disease severity and in the severity of tenderness upon palpation was most apparent in the subgroup of patients who were receiving both ibuprofen and alprazolam. An 8-week, open-label study in which 52 patients received both drugs further documented improvement in outcome measures. These data indicate that treatment with a combination of ibuprofen and alprazolam can be beneficial for some patients with PFS.

Adolescent↗
PubMed1991

Cochlear cultures as a model system for studying aminoglycoside induced ototoxicity.

Light and electron microscopy have been used to evaluate the effects of treating mouse cochlear cultures with the ototoxic aminoglycoside antibiotic neomycin sulphate at concentrations of 0.2 mM and greater for periods of up to 1 hour. Neomycin rapidly induces the formation of numerous, membrane filled blisters on the apical surfaces of the sensory hair cells. Such morphological damage is restricted to the hair cells, and is not observed on the surfaces of supporting cells within the organ of Corti. Hair cells in apical-coil cultures are less sensitive than those in basal-coil cultures, and, at any given point along the cochlea, outer hair cells appear to be more extensively damaged by neomycin than inner hair cells. These morphological effects of neomycin are considerably more severe when the drug is applied in calcium/magnesium free saline, and can be blocked by elevating the saline concentration of either calcium or magnesium. The effects can also be blocked by lowering the temperature to 4 degrees C, but not by either K+ depolarization or the lectin Concanavalin A. The potential value of this culture system as a model for studying aminoglycoside induced ototoxicity is discussed.

Aminoglycosides↗
PubMed1991

The voltage responses of hair cells in the basal turn of the guinea-pig cochlea.

1. Intracellularly recorded voltage responses to tones and to current injection were measured from inner (IHC) and outer (OHC) hair cells in the basal turn of the guinea-pig cochlea. 2. The voltage responses of IHCs to tones are increased by negative current and decreased by positive current. For any given current strength, the decrease in the receptor potential amplitude caused by positive current is less than the increase caused by negative current. This was attributed to the voltage-dependent rectification of the membrane conductance. 3. Estimates of the reversal potential of the receptor current were based on extrapolation of the slopes of the current-voltage relations for potentials more negative than -60 mV. The estimated reversal potentials were close to the measured endolymphatic potential. 4. Negative current increased the IHC membrane time constant and increased the transducer driving voltage. When receptor potentials to low-frequency tones were adjusted for constant driving voltage and for the membrane time constant, the positive DC component of the receptor potential was decreased relative to the AC component by current injection but the DC component in response to high-frequency tones near the best frequency of the IHC (16 kHz) was unchanged by negative current. 5. When compensated for constant driving voltage and low-pass filtering due to the basolateral membrane conductance, the proportion of the transducer conductance open in IHCs at rest is increased by negative current. 6. Negative current injection reduced the positive DC components of OHC voltage responses to low-frequency tones and may make them negative. In some cases negative current injection decreased the amplitude of the OHC receptor potential while positive current injection enhanced it. From these observations it is proposed that negative current injection shifts the operating point of the OHC transducer functions towards a positive, saturating region of the relationship and positive current decreases the proportion of the transducer conductance which is open at rest.

Acoustic Stimulation↗
PubMed1990

Multicenter study of recombinant human erythropoietin in correction of anemia in rheumatoid arthritis.

PURPOSE: To administer recombinant erythropoietin to patients with rheumatoid arthritis who had significant anemia, while monitoring hematologic and rheumatologic clinical responses as well as potential toxicity. PATIENTS AND METHODS: Seventeen patients with rheumatoid arthritis from five rheumatology care settings were studied. The patients had initial hematocrits of 34% or less and stable clinical status, and were not being treated with second-line drugs or corticosteroids. An 8-week randomized double-blind study involving various dosages of recombinant erythropoietin, as well as placebo, was followed by a 24-week open-label study in which dosage could be titrated to achieve a normal hematocrit. RESULTS: In the 8-week randomized study, four of 13 patients who received injections of recombinant erythropoietin showed a hematologic response, arbitrarily defined as at least a 6-unit increase in hematocrit. None of four placebo-treated patients showed a meaningful hematologic response. All 11 patients who completed the subsequent 24-week open-label study reached a normal hematocrit level at some time during the study, and 10 of 11 showed an increase of hematocrit 6 units or greater. At least one adjustment, i.e., an increase, decrease, or omission of the erythropoietin dosage, was required in all patients to maintain the hematocrit at a target range of 35% for women or 40% for men. Meaningful changes were not seen in patients' capacity to perform activities of daily living or pain levels during either the 8-week randomized study or the 24-week open-label study. No adverse effects were associated with recombinant erythropoietin therapy. CONCLUSION: Patients with rheumatoid arthritis showed excellent hematologic responses to recombinant erythropoietin, without toxicity, during careful monitoring for appropriate dosage adjustment, although a meaningful change in rheumatologic clinical status was not seen.

Activities of Daily Living↗
PubMed1990

Stereocilia bundle stiffness: effects of neomycin sulphate, A23187 and concanavalin A.

The effects that the aminoglycoside antibiotic neomycin sulphate, the ionophore A23187 and the lectin Concanavalin A (Con A) have on the steady state stiffness of the hair-cell stereocilia bundle have been studied using organotypic cultures of the early postnatal mouse cochlea. In normal saline, stereocilia bundle stiffness is increased 1.5-2.0 fold by neomycin sulphate, 1.3-1.7 fold by the ionophore A23187 and 3.0-5.0 fold by Con A. In low-calcium saline neither neomycin sulphate nor A23187 cause increases in stiffness, and the stiffness increases elicited by these two agents in normal saline are reversed on washout with low-calcium saline. In normal saline neomycin sulphate has two independent effects on hair cells; one effect is a reversible inhibition of transduction and the other effect is to cause an irreversible increase in bundle stiffness. Neither Con A nor the ionophore A23187 block transduction. No obvious changes in stereocilia bundle morphology are associated with the increases in stiffness caused by neomycin sulphate, A23187 and Con A. Succinylated Con A binds to stereocilia bundles but does not cause an increase in stiffness, suggesting that the stiffness increase caused by native Con A results from receptor cross-linking. The effects of Con A and neomycin are non-additive, saturating concentrations of neomycin sulphate block the effects of low doses of Con A, and pretreatment of cells with succinylated Con A prevents subsequent neomycin sulphate treatment from causing an increase in stiffness suggesting that neomycin sulphate and Con A are acting via a similar mechanism at the cell surface. Ionophore treatment prevents the subsequent application of neomycin sulphate from causing a further increase in stiffness, but when cells are treated with neomycin sulphate followed by ionophore the effects of the two drugs are additive indicating that they are operating via different mechanisms. The possible nature of these mechanisms and their role in the control of steady state stereocilia bundle stiffness are discussed.

Animals↗
PubMed1990

Transient expression of neurofilament protein during hair cell development in the mouse cochlea.

A polyclonal antiserum raised against the 145 kDa neurofilament protein (NFM) has been used to study the distribution of neurofilaments both in organotypic cultures of the early postnatal mouse cochlea and during development of the mouse cochlea in vivo. In the cultures, both the inner hair cells and the outer hair cells are stained by the antibodies, as well as the innervating afferent fibres from the spiral ganglion. In cultures denervated at the time of preparation, neurofilament positive hair cells can still be detected after 7 days in vitro. NFM can also be detected by immunoblotting in such denervated cultures. Characteristic 10 nm diameter, cytoplasmic filaments can also be observed in cultured hair cells using transmission electron microscopy. Immunostaining of cryosections prepared from cochleas at embryonic days 17 and 19, and days 1, 2, 5, 10 and 21 post-partum reveals that hair cells transiently express NFM during their development in vivo. Expression of NFM in hair cells is first detected at embryonic day 19 in the basal region of the cochlea and, by 2 days post-partum, neurofilament positive hair cells are found throughout the entire length of the cochlea. By 10 days post-partum, staining of hair cells begins to diminish and, by 21 days post-partum, NFM can no longer be detected in hair cells.

Animals↗
PubMed1990

Identification of a 275-kD protein associated with the apical surfaces of sensory hair cells in the avian inner ear.

Immunological techniques have been used to generate both polyclonal and monoclonal antibodies specific for the apical ends of sensory hair cells in the avian inner ear. The hair cell antigen recognized by these antibodies is soluble in nonionic detergent, behaves on sucrose gradients primarily as a 16S particle, and, after immunoprecipitation, migrates as a polypeptide with a relative molecular mass of 275 kD on 5% SDS gels under reducing conditions. The antigen can be detected with scanning immunoelectron microscopy on the apical surface of the cell and on the stereocilia bundle but not on the kinocilium. Double label studies indicate that the entire stereocilia bundle is stained in the lagena macula (a vestibular organ), whereas in the basilar papilla (an auditory organ) only the proximal region of the stereocilia bundle nearest to the apical surface is stained. The monoclonal anti-hair cell antibodies do not stain brain, tongue, lung, liver, heart, crop, gizzard, small intestine, skeletal muscle, feather, skin, or eye tissues but do specifically stain renal corpuscles in the kidney. Experiments using organotypic cultures of the embryonic lagena macula indicate that the antibodies cause a significant increase in the steady-state stiffness of the stereocilia bundle but do not inhibit mechanotransduction. The antibodies should provide a suitable marker and/or tool for the purification of the apical sensory membrane of the hair cell.

Animals↗