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Biomedical subjects

M Souter

Publications and source records attributed to M Souter.

10 recordsLinked to original sources

A study of the effects of using different cerebral perfusion pressure (CPP) thresholds to quantify CPP "secondary insults" in children.

Little is known about the incidence of secondary insults, particularly cerebral perfusion pressure insults, in children. The objectives of this study were to assess the duration of CPP insults at three different thresholds in children and to relate CPP insults to outcome. Eighteen children (age < 16, median & mean 8 years) admitted to the Neurointensive Care Unit who had ICP, MAP and CPP continuously monitored were studied. Using the Edinburgh secondary insult analysis program, data was scanned for CPP insults at three different thresholds: CPP < 70 mmHg, < 60 mmHg and < 50 mmHg. Outcome was assessed using the Glasgow Outcome Scale. Thirty percent of the time CPP was between 60 and 70 mmHg, 21% of the time CPP was between 50 and 60 mmHg and 8% of the time the CPP was less than 50 mmHg. Compared with adults, there was more than twice the incidence of CPP insults in all threshold groups. BP remained relatively stable above 70 mmHg across all three CPP threshold groups. However, ICP increased slightly on average from about 13-->17 mmHg when CPP decreased from the < 70 to < 60 mmHg group (p < 0.001). There was a marked increase in ICP to greater than 30 mmHg on average in the CPP < 50 mmHg group (p < 0.001). CPP insults less than 70, 60 and 50 mmHg do occur commonly in children, a larger dataset and possibly longer term follow up measures will be needed to identify potentially treatable physiological factors most effecting the outcome of children.

Adolescent↗

Polarity and signalling in plant embryogenesis.

The establishment of the apical-basal axis is a critical event in plant embryogenesis, evident from the earliest stages onwards. Polarity is evident in the embryo sac, egg cell, zygote, and embryo-suspensor complex. In the embryo-proper, two functionally distinct meristems form at each pole, through the localized expression of key genes. A number of mutants, notably of the model genetic organism Arabidopsis thaliana, have revealed new gene functions that are required for patterning of the apical-basal axis. There is now increasing evidence that two particular modes of signalling, via auxin and cell wall components, play important roles in co-ordinating the gene expression programmes that define determinative roles in the establishment of polarity.

Arabidopsis↗

Gap junctions and connexin expression in the inner ear.

Several different recessive mutations in the connexin26 (Cx26; beta 2) gene have been associated with non-syndromic hereditary deafness. This suggests gap junctions are important to cochlear function. Numerous large gap junctions are present between adjacent supporting cells in both the vestibular and auditory sensory epithelia of the mature inner ear. In vestibular organs, Cx26 is highly expressed, but antibodies of Cx32 (beta 1) also label the supporting cells. In the organ of Corti of the cochlea, Cx26 is the predominant connexin isoform; neither Cx32 nor Cx43 (alpha 1) can be detected by immunohistochemistry. One role for gap junctions between supporting cells may be to provide a pathway for the rapid removal of ions away from the region of the sensory cells during transduction in order to maintain sensitivity. In the cochlea gap junctions are also associated with the basal cells of the stria vascularis, an ion-transporting epithelium that maintains a positive electrical potential in the potassium-rich endolymph fluid which bathes the apical surfaces of the sensory 'hair' cells and which is crucial for auditory transduction. Gap junctions are present between fibrocytes in the spiral ligament that underlies the stria vascularis, and between these fibrocytes and strial basal cells. During cochlear development, the initial formation and subsequent increase in size and number of gap junctions in the stria vascularis coincides with the initial generation and rise of the endocochlear potential. This and other evidence suggests that one role of gap junctions in the cochlea is to provide a pathway for passage of ions to maintain endolymph and, thus, auditory acuity. Mutations to Cx26 could, therefore, disrupt this ion circulation, resulting in deafness.

Amino Acid Sequence↗

Intercellular junctional maturation in the stria vascularis: possible association with onset and rise of endocochlear potential.

The postnatal maturation of intercellular junctions of marginal and basal cells of the stria vascularis was examined in the gerbil using thin sections and freeze fracture techniques. Immunohistochemical methods were used to determine the presence of Na,K-ATPase postnatally. The onset and growth of endocochlear potential (EP) was also measured. In marginal cells, the apical surface and junctional region around the apical pole of the cell was found to have adult-like characteristics by the time of onset of EP, whilst the increase in staining for Na.K-ATPase temporally coincided with an increasing density of intra-membrane protein particles on the infoldings of marginal cell lateral membranes. Maturation of the junctional specialisations of the basal cells was found to correspond temporally with the period of onset and rise of EP. Tight junctions between basal cells first appeared as small, broken strands composed of widely spaced particles at 6 days after birth (DAB). These junctional strands increased in number and in particle density until adult-like at 16 DAB when they covered large areas of the basal cell lateral membrane. Gap junctions on the apical membrane of basal cells first appeared as small patches of loosely packed junctional elements at 6 DAB. Between 8 and 16 DAB the area of membrane occupied by the gap junctions increased, reaching a mature conformation by 18 DAB. The results suggest that EP maturation is dependent upon the development of sealing between the basal cells by tight junctions and also the establishment and development of gap junctions in the apical plasma membrane of basal cells, associated with intermediate cells.

Age Factors↗

Postnatal maturation of the organ of Corti in gerbils: morphology and physiological responses.

The organ of Corti, the sensory epithelium of hearing in mammals, matures postnatally in the gerbil. Quantitative analyses of the postnatal development of the organ of Corti, including supporting cells and the basilar membrane, were carried out. The morphological study confirmed that maturation of the sensory cells proceeds with a base-to-apex gradient, with the outer hair cells appearing to mature before the inner hair cells. Maturation of the supporting cells and the basilar membrane commenced first in the middle turn. Expansion of the second row of Deiters' cells began at 6 days after birth in the middle turn, before enlargement of the pillar cell heads at 8 days postnatally. Pillar cell head enlargement continued until 20 days postnatally in the middle turn. The tunnel of Corti and spaces of Nuel appeared first in the middle turn between 8 and 10 days postnatally. The maturation of the basilar membrane involved the thickening of the central hyaline layer and a reduction in the epithelial cells on the tympanic aspect. This process continued until about 20 days after birth. The cochlear microphonic potential, whole nerve action potential, and stimulus frequency otoacoustic emissions were recorded from 12 days after birth onward and related to changes in organ of Corti morphology. The results show that changes in the accessory structures continue throughout the period of onset and development of cochlear responses between 12 and 20 days after birth, and may therefore influence the micromechanical responses of the organ of Corti to acoustic stimuli during this period.

Animals↗

Structural development of sensory cells in the ear.

The hair cells of the auditory and balance systems of the inner ear have precise structures and orientations related to function. Hair cells differentiate from a homogenous cell population with the initiation of afferent synaptogenesis and appearance of the apical hair bundle being the first definitive structural sign of hair cell development. The cytoskeletal network then develops and the intercellular membrane junctions become more complex. As auditory function is established in mammalian cochlear hair cells, the lateral membrane acquires certain specializations. Accompanying this there is a change from afferent to efferent innervation of outer hair cells.

Journal Article↗

Stimulus frequency otoacoustic emissions from guinea pig and human subjects.

Stimulus frequency otoacoustic emissions (SFOAEs) have previously been recorded from human subjects by the suppression of a continuous stimulus tone generated OAE by a second tone (Kemp et al., 1990). This study presents comparative data from guinea pig and human subjects using a similar method. Differences between human and guinea pig responses to suppressor tones of higher frequency than the stimulus tone are reported. The most effective suppressors of the SFOAE in human subjects was found to be a tone of the same or slightly higher frequency than the continuous stimulus tone. In guinea pigs, this stimulus condition was found to be less effective than higher-frequency suppressors. Large phase changes were found in the SFOAE from guinea pigs when higher-frequency suppressors were employed. These were not seen in the human data. Changes in the SFOAE latency from guinea pig ears were also found as the suppressing tone frequency moved above that of the stimulus tone. These level and phase effects, when taken together with latency changes, may be indicative of the differing contributions of stimulus-place generated OAEs and those from more basal elements to the total emission recorded in the meatus in guinea pig. The results are discussed in view of the known species differences in the tuning characteristics at the frequency region studied.

Acoustic Stimulation↗

Postnatal development of membrane specialisations of gerbil outer hair cells.

Using a combination of freeze-fracture and thin sections, this study examines the maturation of the membrane specialisations of the gerbil outer hair cells (OHC) between 2 and 16 days after birth (DAB). The apical membrane, the junctional region around the neck of the cell, and the lateral and basal membranes are described. The results suggest a sequential development of the different components of the lateral wall. Intramembrane protein particles (IMP), the putative OHC motor elements, were found to be present at low density at 2 DAB and increased in density from 2200 IMP/microns 2 at 2 DAB to 4131/ microns 2 at 8 DAB. OHCs have been reported as showing electromotility from 8 DAB onward. IMPs continue to increase in density until mature values are attained at 16 DAB. Sub-surface cisternae did not appear until 8 DAB, with a single layer being complete by 10 DAB. Pillar structures, proposed to be related to the cytoskeletal lattice, first appear at 10 DAB. The apical membrane of the immature hair cell is characterised by the presence of pits related to the endocytosis of vesicles, and tip-links between stereocilia, thought to be associated with sites of ion channel opening, are present at 2 DAB. The junctional region comprises two areas which mature at differing rates: an apical-most region which attains an adult-like appearance by 8 DAB and a basal-ward region which continues to increase in complexity until mature at 16 DAB. The functional significance of the results are discussed in relation to the possible roles of the junctional regions and the proposed sites of the OHC motor elements.

Aging↗

Suppression of stimulus frequency otoacoustic emissions by contralateral noise.

The effect of different bands of contralaterally presented noise at low and moderate intensities on stimulus frequency otoacoustic emissions (SFOAE) from human ears is examined. A SFOAE evoked by a continuous stimulus tone and suppressed by a second tone to produce an SFOAE residual was chosen as the probe to determine the effect of the efferent input. At low levels of contralateral noise, a band centred on the ipsilateral stimulus frequency was the most effective suppressor of the SFOAE residual. For higher levels of the contralateral stimulus, noise bands containing higher frequency components produced most reductions in the SFOAE residual. Small changes in the phase of the SFOAE residual during the contralateral noise were also recorded. Increases in the SFOAE residual onset latency were also found to be small, being around 1 ms. In some cases increases in the level of the SFOAE residual produced by low-frequency suppressors were recorded during the contralateral noise presentation. The results are discussed in the context of current knowledge of the functioning of the auditory efferent innervation, and it is suggested that the method of evoking SFOAEs presents a viable method for determining the effect of efferent stimulation on cochlear mechanics which also allows possible artifact contamination to be readily identified.

Acoustic Stimulation↗

A new rapid component in the cochlear response to brief electrical efferent stimulation: CM and otoacoustic observations.

The onset and time course of cochlear response changes induced by brief electrical stimulation of medial fibres of the OCB have been studied in detail in guinea pig. Changes in both cochlear microphonic and otoacoustic responses begin within 10 ms of electrical excitation. The sensitive differential technique employed has allowed the use of very short and weak electrical stimulations. The effects of induced levels of activity close to those normally present are reported. After transient electrical excitation (a single 100 microseconds, 20 mu amp shock), changes in the cochlear microphonic response reached a maximum around 20 ms. Thereafter the perturbation decayed initially with a time constant between 30 and 45 ms, then more slowly with a time constant greater than 100 ms. For more intense but still brief excitation the initial response decay was even more rapid often resulting in a bimodal decay pattern - a discrete 'burst' and a 'slow tail'. Otoacoustic data was similar. Only the slow tail component corresponds to previously reported effects and we suggest that it may be associated with overstimulation of the efferent system.

Acoustic Stimulation↗