Mammalian cells become more susceptible to radiation-induced death and mutagenesis when restricted in their production of the natural polyamines putrescine, spermidine and spermine. The effects of polyamine deprivation are reversed by N-(2-mercaptoethyl)-1, 3-diaminopropane (WR1065), a simple aminothiol that has been extensively studied for its radioprotectant properties. Because this compound and its oxidized derivative WR33278 bear some resemblance to the polyamines, it was hypothesized that radioprotection by WR1065 or its metabolites is derived, at least in part, from their ability to supplement the natural polyamines. To evaluate the ability of these aminothiol compounds to emulate polyamine function in intact cells, rat liver hepatoma (HTC) cells were treated with radioprotective doses of WR1065; the ability of this compound to affect various aspects of normal polyamine metabolism was monitored. Although cellular WR1065 was maintained at levels exceeding those of the polyamines, this aminothiol did not have any polyamine-like effect on the initial polyamine biosynthetic enzyme, ornithine decarboxylase, or on polyamine degradative reactions. On the contrary, treatment with relatively low levels of WR1065 resulted in an unexpected increase in putrescine and spermidine synthesis. WR1065 treatment enhanced the stability, and consequently the activity, of ornithine decarboxylase. This stabilization seems to result from a WR1065-induced delay in the synthesis of antizyme, a critical regulatory protein required in the feedback modulation of polyamine synthesis and transport. The increase in cellular spermidine induced by WR1065 might explain its antimutagenic properties, but is probably not a factor in protection against cell killing by radiation. This is the first evidence that compounds can be designed to control polyamine levels by targeting the activity of the regulatory protein antizyme.

The purpose of this experiment was to determine whether age-related differences would be observed for discrimination of synthesized, 5-formant consonant-vowel syllables that differed in voicing onset time (VOT) of the initial consonant. Just noticeable differences (JNDs) were measured relative to the end points of the stimulus continuum, using a "same"-"different," adaptive procedure with trial-by-trial feedback/reinforcement and "catch" trials, in which members of the stimulus pair were identical syllables. 6-8-year-old children required significantly longer VOTs for syllabic discrimination than did adults. Adults' JNDs relative to [pa] at the end of the stimulus continuum with longer VOTs were significantly larger than their JNDs relative to [ba], as would be expected on the basis of psychoacoustic considerations, but neither 6-8-nor 8-11-year-old children showed this trend. Performance on "catch" trials for both groups of children was significantly poorer than for adults. Outcomes corresponded to results of other investigations that have reported that children require more acoustic information than adults to achieve the same performance criterion.

The purpose of this experiment was to determine whether age-related differences would be observed for discrimination of synthesized, 5-formant consonant-vowel syllables that differed in voicing onset time (VOT) of the initial consonant. Just noticeable differences (JNDs) were measured relative to the end points of the stimulus continuum, using a "same"-"different," adaptive procedure with trial-by-trial feedback/reinforcement and "catch" trials, in which members of the stimulus pair were identical syllables. 6-8-year-old children required significantly longer VOTs for syllabic discrimination than did adults. Adults' JNDs relative to [pa] at the end of the stimulus continuum with longer VOTs were significantly larger than their JNDs relative to [ba], as would be expected on the basis of psychoacoustic considerations, but neither 6-8-nor 8-11-year-old children showed this trend. Performance on "catch" trials for both groups of children was significantly poorer than for adults. Outcomes corresponded to results of other investigations that have reported that children require more acoustic information than adults to achieve the same performance criterion.

Adaptive test procedures were employed in a field study to determine just-noticeable differences relative to each endpoint of an eight-item, /ba/pa/ continuum of five-formant, synthesized syllables that differed in 5-ms VOT steps. Difference limens for young adults were smaller than for 8–10 year-old children, for whom jnds, in turn, were smaller than for 6–7 year-old children. Difference limens at the /pa/ end of the continuum were larger than those for /ba/, for each age level. These age-related differences in VOT discrimination, in the presence of essentially 100% correct performance for all Ss on a clinical test of word discrimination, resemble previously reported age-related differences in discrimination of the place of articulation feature [L. L. Elliott et al., J. Acoust. Soc. Am. 70, 669–667 (1981)]. Performance of normally hearing, learning-disabled children will also be discussed. [Work supported, in part, by NINCDS.]

We have previously described age-related differences in VOT discrimination [L. L. Elliott et al., J. Acoust. Soc. Am. Suppl. 1 77, S96 (1985)] and discrimination of the place of articulation feature [L. L. Elliott et al., J. Acoust. Soc. Am. 70, 669–677 (1981)] when just-noticeable differences among five-formant synthesized CV syllables are measured using adaptive test procedures. This is the first report of a larger study which also measured vocabulary level, receptive language skill, speech articulation, etc. As previously reported, older children demonstrated smaller just-noticeable differences for syllable discrimination than younger children. Of great interest, however, was the finding that, among normals, there were higher correlations between syllable discrimination and speech production for 6–8 year olds than for 8–11 year-old children. Preliminary factor analyses revealed different factor structures for learning-disabled 8–11 year olds, as compared to their normal age mates. For example, for these learning-disabled Ss, the two measures of VOT discrimination defined one factor while the two measures of the place features, plus the measure of receptive vocabulary, defined another factor. In contrast, the measures of syllable discrimination were distributed across four factors for the older, normal Ss. [Work supported, in part, by NINCDS, NIH.]