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Biomedical subjects

J C Saunders

Publications and source records attributed to J C Saunders.

At least 73 records · Page 4Linked to original sources

Recovery of the basilar papilla following intense sound exposure in the chick.

Newly hatched chicks were exposed to a 900-Hz tone at 120 dB SPL for 48 hours, then sacrificed, along with unexposed controls, at intervals of 0-15 days following exposure. Examination of the basilar papilla by scanning electron microscopy demonstrated a 32% loss of hair cells within the lesion area with substantial shrinkage of the apical surfaces of the survivors. Within days, the papilla returned to a nearly normal appearance, and new hair cells were seen, but the number of new cells was only a fraction--approximately 22%--of the number lost. Expansion of the apical surfaces of the surviving cells to larger than normal size was a major factor in the recovery of the papilla.

Animals↗

Increased stratum corneum turnover induced by subclinical irritant dermatitis.

The chronic effects of the irritant sodium lauryl sulphate (SLS) on stratum corneum (SC) barrier function, determined by transepidermal water loss (TEWL) measurements and on epidermal cell kinetics, estimated by stratum corneum turnover time (SCTT) determination (dansyl chloride staining method), were investigated in 18 healthy female volunteers. SLS (7.5%) was applied without occlusion for 20 min once daily, over a period of 3 weeks (5 days a week) on dansyl chloride-stained skin and on untreated skin. SCTT of untreated skin (19.3 +/- 0.8 days; mean +/- SEM) was not changed by daily treatment with water (control) (19.3 +/- 2.0) but was significantly reduced by SLS (10.9 +/- 0.6; P less than or equal to 0.0001; compared to controls). However, TEWL was increased in SLS-treated sites 1.5-fold after 4 days of treatment (5.3 +/- 0.6 vs. 3.5 +/- 0.3; P less than 0.001). At the end of the second week, TEWL was increased 2.6-fold and after 3 weeks TEWL was 3.3 times higher than in controls 13.0 +/- 1.6 vs. 3.9, P less than or equal to 0.0001). The intensity of SLS-induced irritation as measured by TEWL was significantly correlated with baseline TEWL (r = 0.50; P less than or equal to 0.02) and significantly negatively correlated with SCTT of SLS treated sites (r = -50; P less than or equal to 0.02) but not with SCTT of untreated skin (r = 0.19).

Adolescent↗

Recovery of auditory function following intense sound exposure in the neonatal chick.

We report the changes in auditory function that occurred at selected intervals following exposure to an intense pure-tone stimulus. One day old chicks were exposed to a 0.9 kHz tone for 48 h at 120 dB. At 0, 1, 3, 6, 9, 12 and 15 days after exposure, cochlear nucleus sound-evoked potentials were used to assess threshold sensitivity and frequency selectivity. Immediately after removal from the pure tone a threshold shift of 60 dB relative to age-matched controls was measured. The sharpness of tuning curves, as measured by Q10 dB, decreased by over 50%. By post-exposure day 15, near complete recovery of function was seen, with the greatest recovery occurring within the first three days. We relate these results to recent reports of structural recovery on the basilar papilla of the chick.

Animals↗

Structural changes in hair cells after incubation in tissue culture medium.

A great deal of work is presently being pursued with in vitro preparations of isolated single hair cells or isolated segments of the cochlear sensory surface. In this study we evaluate the appearance of hair cells along the neonatal chick basilar papilla that have been freshly dissected and placed in culture medium for between one and six hours. Quantitative measures of the apical hair cell surface revealed that the number of cytoplasmic protrusions was minimal and that surface area was well preserved in the one and three hour samples. By 6 h, the proportion of hair cells showing cytoplasmic protrusions significantly increased, as did the surface area of the hair cells. In this preparation, it appears that physiologic studies can be conducted on cells with a healthy appearance for at least 3 h after sacrifice.

Adaptation, Physiological↗

The design, calibration, and use of a water microjet for stimulating hair cell sensory hair bundles.

The design, calibration, and use of a noninvasive, noncontact device for stimulating hair cell hair bundles in vitro are described. This device employed a piezoelectric crystal, driven at high frequencies, to generate sinusoidal pressure in a contained fluid volume. The pressure was propagated to the tip of a glass micropipette and the oscillating water jet stimulus produced at the tip was used to stimulate sensory hair bundles. The movements of glass microbeads, caught in the oscillating pressure field of the water jet, provided a means of calibrating this stimulus. The linearity of the jet, its waveform and frequency response, the influence of pipette shape and tip diameter, as well as models to explain the operation of the water jet, are described. The use of this stimulus for measuring hair bundle micromechanics at high frequencies is then demonstrated.

Animals↗

When is a residue not a residue?

Residues of veterinary products in food animals have been the subject of much debate in recent years. This paper attempts to define and classify what is meant by the term 'residue' and to discuss the toxicological significance of various types of residues and how they may be controlled to ensure that no hazard results to consumers.

Adolescent↗

Hair cell loss and regeneration after exposure to intense sound in neonatal chicks.

Neonatal chicks (between 1 and 3 days of age) were exposed to an intense pure tone for 48 hours, then killed immediately after removal from the sound, or 14 days later. Nonexposed age-matched animals served as controls. The inner ear was removed and the auditory receptor organ (the basilar papilla) was prepared for evaluation by scanning electron microscopy. The site of injury on the papilla was described in terms of hair-cell loss and location. The ears with no recovery showed a discrete lesion area, within which there was complete disruption of the hair-cell field and a 35% loss in hair cells. After 14 days' recovery, no hair cell loss could be detected, though the lesion could still be recognized by the disorganization of hair cells in the previously injured area. These data demonstrate hair-cell restoration after severe acoustic injury from intense sound exposure in the neonatal ear.

Animals↗

From animal to molecule: aspects of the biology of insulin-like growth factors.

The synthesis of IGF-II mRNA in sheep foetal tissues is considerably higher than IGF-I. IGF-II probably has a paracrine role in the foetus; however it is likely that IGF-I originates mainly from the foetal liver and has an endocrine function. Although in the adult system IGF-I is tightly bound to serum carrier proteins it is potentially biologically active. Galactopoiesis in the goat mammary gland provides a useful model for demonstrating the importance of circulating IGF-I as a mediator of GH action. Ligand-receptor interactions involved in the stimulation of Swiss 3T3 fibroblasts by IGF-I, II and insulin were examined. It was found that the potency of binding to type I receptors was IGF-I greater than IGF-II much greater than insulin by competitive binding assays and chemical cross-linking studies, and that some cell lines secrete an IGF binding protein which is specific for IGF-I and II and which acts as an inhibitor in cellular binding assays. Maximal stimulation of DNA synthesis induced by IGF-I, II and insulin in the presence of synergising mitogens were similar. While the actions of the IGFs were consistent with type I receptor binding insulin appeared to act through its own receptor. The reduction of EGF receptor affinity following the addition of IGF-I and insulin to 3T3 cells may involve a protein kinase that is not sensitive to phorbol esters. 3T3 cell nuclei contain endogenous inositol phospholipids and their corresponding kinases and monoesterases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Spectral and temporal response patterns of single units in the chinchilla dorsal cochlear nucleus.

Spectral and temporal response patterns to pure-tone stimuli were collected from single units in the dorsal cochlear nucleus of anesthetized chinchillas. The spectral response profiles were divisible into groups based on the balance of excitation and inhibition. Temporal responses were characterized in chloralose-anesthetized animals by collecting PST-histograms. There appeared to be no simple one-to-one relationship between a unit's spectral and its temporal response pattern. Excitatory spectral responses were generally sharply tuned areas resembling those of auditory nerve fibers. However, unlike the latter, the majority of these had chopper or pauser/buildup temporal responses. Inhibitory spectral responses were of two distinct types: one included lateral inhibitory areas flanking the tuned excitatory areas which occasionally invaded the latter creating a nonmonotonic excitatory response at the unit's characteristic frequency. The other included sharply tuned inhibitory areas. The characteristic frequencies of these units were found to be in close correspondence with those of sharply tuned excitatory units from the same penetration suggesting that these inhibitory units were tonotopically mapped in the same register as tuned excitatory units. The spectral response patterns were studied with three types of anesthesia: ketamine/xylazine, dial/urethane, and chloralose. In each of these groups the patterns were similar. However, the proportions of units showing inhibition was strongly dependent on the choice of anesthetic agent with chloralose yielding the highest proportions (59%) and ketamine/xylazine yielding the lowest (29%).

Action Potentials↗

Hair cell damage produced by acoustic trauma in the chick cochlea.

Examination of pure-tone acoustic damage in the chick basilar papilla revealed that the location and extent of hair cell damage was a function of both the stimulus intensity and the age at which the chicks were exposed. Scanning electron microscopic evaluation of noise-exposed cochleae at post-hatching days 1, 10 and 30 permitted the identification of discrete regions of damage, including hair cells with stereocilia injuries as well as those lost from the epithelium. The hair cell damage was tonotopically distributed along the cochlea according to frequency. However, for each exposure frequency two distinct sites of damage were often produced, and their locations were correlated with stimulus intensity. At low intensities, a longitudinal strip of hair cell damage ran along the superior edge of the basilar papilla. As exposure intensity increased, a second damage site developed along the inferior edge of the basilar papilla, distal to the longitudinal strip. This second type of damage initially took the form of a series of laterally-oriented wedges, but at higher intensities, the wedges coalesced to form a large crescent-shaped patch of damage. The location of the damage sites for each frequency did not shift with age. However, there were differences in the extent and position of the damage which could be correlated with stimulus intensity and with changes in middle ear admittance during development [(1983) Development of Auditory and Vestibular Systems, pp. 3-25. Editor: R. Romand. Academic Press, New York]. These results suggest that developmental changes in the location and extent of hair cell damage depend on the effective stimulus intensity reaching the cochlea, rather than on alterations in the frequency coding of the hair cells.

Acoustic Stimulation↗

Immunocytochemical and quantitative studies of Na+,K+-ATPase distribution in the developing chick cochlea.

Immunocytochemical methods were used to examine cryosections of the embryonic and neonatal chicken cochlea in order to study the histological distribution of the Na+,K+-ATPase molecule during maturation. In complementary studies the Na+,K+-ATPase capacity of microdissected freeze-dried substructures of the cochlea was determined fluorometrically. The dark cell of the tegmentum vasculosum exhibited intense immunochemical staining of the convoluted basolateral infoldings. The adjacent light cells demonstrated very little staining. The plasma membrane of the hair cell was also stained as were the first order auditory neurons, including the cell soma. The homogene cells and the supporting cells were unstained. The dark cell was only lightly stained with the antibody at stage 45 but became more intense and selective by the seventh postnatal day. The other cells of the cochlear duct exhibited specific immunofluorescent staining of their plasma membranes from stage 45 onwards and the fluorescent intensity did not change. The tegmentum vasculosum exhibited very high activities of the Na+,K+-ATPase enzyme relative to the other structures of the cochlea. Furthermore, a pronounced gradient of enzymatic activity was detected longitudinally. The proximal tip (or high-frequency end) had a sixteen-fold greater capacity for Na+- and K+-dependent ATP hydrolysis relative to the distal tip (or low-frequency end). The appearance of this enzyme in the tegmentum vasculosum during the development of the cochlea paralleled the known rate of improvement in hearing thresholds.

Animals↗

Antianaphylactic benzophenones and related compounds.

The synthesis and biological properties of 85 benzophenones and related compounds are described. The majority of the compounds inhibit the release of leukotrienes (LT) C4 and D4 in vitro from sensitized guinea pig chopped lung. In addition, some of the compounds inhibited the release of LTs from passively sensitized human chopped lung and protected guinea pigs from the effects of anaphylaxis in a modified Herxheimer test.

Anaphylaxis↗

Threshold sensitivity and frequency selectivity measured with round window whole nerve action potentials in the awake, restrained chinchilla.

Chronic electrodes, placed on the round windows of four adult chinchillas, were used to measure whole-nerve action potential (AP) thresholds and tuning curves. The AP quiet thresholds were within 17 dB of thresholds measured by behavioral methods and within 3 dB of those measured by other evoked response procedures. The AP tuning curves, obtained by a simultaneous masking procedure, were also similar to previously measured tuning curves in the chinchilla. These results indicate that long-term indwelling electrodes can be successfully placed on the chinchilla round window and used to measure threshold sensitivity and frequency selectivity. Recordings from these electrodes could be used in a variety of situations and may be particularly useful in studying the effects of noise on the cochlea.

Animals↗

The developmental appearance of a major basilar papilla-specific protein in the chick.

The sensory epithelium of the chick cochlea, the basilar papilla, contains a major protein of approximately 23,000 daltons. This protein was as abundant as actin in the papilla, yet could not be found in significant quantities in any other cochlear tissue. The protein appeared at a time in development when other studies have shown that the chick embryo develops peripheral auditory competence. These observations suggest a role for this protein in cochlear function.

Age Factors↗

Changes in stereocilia micromechanics following overstimulation in metabolically blocked hair cells.

Previous studies have demonstrated that stereocilia micromechanics change during exposure to intense stimulation, and then recover after the stimulus has ended. These changes were associated with a loss of stiffness in the sensory hair bundle. The patterns of growth and recovery in these data suggest that active cellular processes control and limit these phenomena. The present investigation further supports this suggestion. The effects of intense stereocilia stimulation were examined before and after the hair cells were metabolically blocked by cooling or by poisoning with NaCN. In normal cells threshold shift increases with exposure duration, reaching a plateau within 5 to 6 min. Moreover, a post-exposure recovery of the threshold was also noted in the control cells within 15 min. In contrast threshold shift after the first minute in the metabolically blocked cells increased monotonically during the exposure without any indication of a plateau. Similarly, no post-exposure recovery of threshold shift was seen in the stereocilia bundles. These data support the hypothesis that metabolic processes in the region of the sensory hairs are important for limiting the loss of stiffness during exposure, as well as for restoring stiffness during recovery.

Animals↗

Changes in middle-ear input admittance during postnatal auditory development in chicks.

Admittance at the tympanic membrane was measured in one ear of 73 chicks in 8 age groups between 1 and 150 days post-hatch. Admittance at 7 frequencies (0.66-1.8 kHz) was calculated from measurements of the magnitude and phase angle of sound pressure in front of the tympanic membrane. The results show that admittance magnitude at all frequencies increased exponentially with age during the first 70 days of life. The admittance angle also changed systematically with age. These developmental events may be related to changes in the compliance and resistance of the tympanic membrane.

Acoustic Impedance Tests↗

Recovery of threshold shift in hair-cell stereocilia following exposure to intense stimulation.

The isolated cochlear coil preparation was used to study changes in hair-cell stereocilia stiffness before and after overstimulation. Results were obtained from inner and outer hair cells in the apical and middle turns of the guinea pig cochlea. The stereocilia bundles were stimulated with an oscillating water jet and their movements were identified with stroboscopic illumination in a differential interference contrast microscope. The intensity of the water jet could be varied in decibel steps and the attenuation needed to achieve a 'visual detection level' threshold of movement was the criterion response throughout. Pre-exposure thresholds were sampled, the stereocilia bundle was overstimulated, and thresholds were measured during a recovery interval. Sensory hair bundles on all hair-cell rows showed a loss in stiffness following overstimulation which was proportional to the impedance of the stereocilia bundle. During recovery, stiffness increased and often showed a return to the pre-exposure threshold level. The results demonstrated that the loss of sensory hair stiffness following overstimulation recovered with the passage of time. The magnitude of the initial threshold shift, however, was related to the exposure conditions, cochlear location, and the impedance of the sensory hair bundle. The rate of recovery appeared to be independent of cochlear location, hair-cell row, or exposure conditions.

Acoustic Stimulation↗