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Developmental changes in spherical cell sizes were measured in the ventral cochlear nucleus (VCN) in normal guinea pigs aged 2 days and 2, 7 and 12 weeks to establish the time course of postnatal neuronal growth, as a baseline for our experimental work. A continued growth of spherical cell size was observed in the VCN up to 7 weeks postnatally. Animals were unilaterally deafened by cochlear perfusion with kanamycin sulphate at ages 1 and 6 weeks. After 6 weeks survival the spherical cells were measured in the VCNs of both sides. Unilateral deafferentation at both ages caused an ipsilateral reduction in spherical cell size, neurons of the younger group being smaller than in the older. On the contralateral side these cells in the older group were larger than age-matched controls while in the younger group there was no difference compared with age-matched controls. These findings suggest that the results of deafferentation are age-dependent, and may indicate an ability of the neural circuitry to adapt to the loss of sensory input on the other side.

An example of a homogeneously staining region (hsr), occurring in an acute myeloid leukaemia (M5) on chromosome 11 in the region of bands q23-q24, has been analysed. In situ hybridisation using yeast artificial chromosome (YAC) DNA demonstrated that the amplification did not include the CD3 gene cluster and did not affect the human trithorax gene known to be disrupted by translocations at 11q23. In contrast, the amplification was shown to include the sequence D11S543 which has been previously mapped to chromosome band 11q24. High resolution analysis using confocal microscopy allowed the individual amplicons to be visualised, and it was shown that the hsr consisted of an 8-fold amplification of the region surrounding the probe D11S543. From previous estimates of human chromosome size it was possible to calculate that the hsr was composed of amplicons approximately 10 megabases in length. It was concluded that the region amplified did not extend as far as the translocation breakpoints occurring at 11q23 in acute leukaemias.

Stimulation with alternating current at the round window causes an accelerated uptake of extracellular HRP by endocytotic vesicles in inner hair cells at the base of the stimulated cochlea, near the site of the electrode, but does not noticeably affect uptake into outer hair cells. After unilateral electrical stimulation, efferent endings on outer hair cells at the cochlear base show increased vesicular and endosomal labelling in both the ipsilateral and contralateral ears. It is concluded that round-window electrical stimulation increases afferent synaptic activity in inner hair cells near the electrode site, and also increases synaptic activity in OHC efferent endings, not only of the ipsilateral cochlea but also of the corresponding region of the contralateral cochlea. Rapid diffuse cytoplasmic labelling of inner and outer hair cells also occurs sporadically in both stimulated and unstimulated cochleae. However, in efferent terminals, diffuse labelling is restricted to stimulated animals, and occurs bilaterally, in corresponding basal regions of the cochlea.

A strategy for the isolation of DNA probes from small numbers of flow-sorted human chromosomes has been developed. A lymphoblastoid cell line carrying the 22q- derivative chromosome product of the constitutional t(11;22) translocation was used as the source of chromosomes. Synthetic oligonucleotide primers, based on the consensus Alu sequence, were used to amplify inter-Alu sequence from 500 flow-sorted 22q- derivative chromosomes. The amplified sequences were cloned into a plasmid vector by blunt-end ligation, yielding clones with inserts in the range of 400 to 1000 bp. Approximately 70% of these clones hybridized to human DNA as single-copy probes. To identify clones derived from chromosome 11, the library was screened with a heterogeneous probe prepared by Alu-PCR amplification from the DNA of a somatic cell hybrid containing one homology of chromosome 11. All the positive clones found were mapped to within the q23-q25 region of chromosome 11 known to be translocated onto the 22q- derivative chromosome. Further mapping studies showed that most of these probes (7/8) lay between the breakpoints for the t(4;11) translocation of acute lymphocytic leukemia and the t(11;22) of Ewing sarcoma. Thus, the use of Alu-PCR on the small derivative chromosome 22q- has provided a greatly enriched source of probes to region 11q23, a part of the genome that is currently of great interest. This approach will be particularly appropriate to small numbers of chromosomes when high specificity rather than total representation is required.

The possible effects of incubator noise on the hearing of premature babies have long been debated. The type of hearing loss found in 12 low-birthweight children was examined; and the variable noise level in regularly used incubators was measured. This noise, applied to guinea pigs continuously during their second week after birth, was shown histologically to destroy a proportion of the sensory cells in the cochlea. Adult guinea pigs, however, were not vulnerable in this way. The conclusion is that there is definite circumstantial evidence of the damaging effect of many incubators on the hearing of premature infants.

We have developed a system for single-channel electrical stimulation of the totally deaf. The patient wears a removeable electrode assembly which stimulates the cochlear promontory and can be inserted and removed like the earmould of a hearing aid. This approach minimises the risk of mechanical or electro-chemical damage to structures within the cochlea. Charge-balanced stimulation is used to present those speech pattern elements that are matched to the patients' lipreading needs and their new sensory abilities. Objective tests show improvements both in patients' perceptive and productive abilities.

Guinea pigs aged one week were exposed to white noise at a maximum of 76 dB SPL for 7 days and were then killed 3, 8 and 16 weeks later for histological examination of the cochlea by the surface preparation method. Appreciable increases in outer hair cell losses were observed in the apical turn 3/3 1/2, chiefly in the outer two rows, between the 3rd and 8th week, but not between the 8th and 16th week. No significant losses were seen in control groups corresponding to 3- and 8-week periods, although in the control group of 16 weeks' survival, small deficits, attributable to natural ageing, were seen in the apical half-turn, 3 1/2.