Changing meaning causes coupling changes within higher levels of the cortical hierarchy.

Processing of speech and nonspeech sounds occurs bilaterally within primary auditory cortex and surrounding regions of the superior temporal gyrus; however, the manner in which these regions interact during speech and nonspeech processing is not well understood. Here, we investigate the underlying neuronal architecture of the auditory system with magnetoencephalography and a mismatch paradigm. We used a spoken word as a repeating "standard" and periodically introduced 3 "oddball" stimuli that differed in the frequency spectrum of the word's vowel. The closest deviant was perceived as the same vowel as the standard, whereas the other 2 deviants were perceived as belonging to different vowel categories. The neuronal responses to these vowel stimuli were compared with responses elicited by perceptually matched tone stimuli under the same paradigm. For both speech and tones, deviant stimuli induced coupling changes within the same bilateral temporal lobe system. However, vowel oddball effects increased coupling within the left posterior superior temporal gyrus, whereas perceptually equivalent nonspeech oddball effects increased coupling within the right primary auditory cortex. Thus, we show a dissociation in neuronal interactions, occurring at both different hierarchal levels of the auditory system (superior temporal versus primary auditory cortex) and in different hemispheres (left versus right). This hierarchical specificity depends on whether auditory stimuli are embedded in a perceptual context (i.e., a word). Furthermore, our lateralization results suggest left hemisphere specificity for the processing of phonological stimuli, regardless of their elemental (i.e., spectrotemporal) characteristics.

Are bone scans necessary in men with low prostate specific antigen levels following localized therapy?

PURPOSE: The prostate specific antigen level at which to recommend a bone scan after treatment of early prostate cancer is controversial. We identified the incidence of bone metastases at varying prostate specific antigen levels in asymptomatic men following radical prostatectomy, radiation therapy and watchful waiting. MATERIALS AND METHODS: Data were obtained from the Early Prostate Cancer trial comparing placebo with bicalutamide in addition to standard care for localized prostate cancer. As part of the trial patients were required to have routine bone scans regardless of prostate specific antigen levels. The prostate specific antigen levels were divided into subgroups and the incidence of positive bone scans was calculated for each group. RESULTS: The incidence of positive bone scans in patients treated with watchful waiting and given bicalutamide or placebo was low (0.7% to 3.2%) at prostate specific antigen levels less than 20 ng/ml. At greater than this level the sample sizes were smaller but there was a significant increase in the incidence of positive bone scans. In the groups treated with radiation therapy or radical prostatectomy, regardless of the addition of bicalutamide, the incidence of positive bone scans was low (0.2% to 1.4%) at prostate specific antigen levels less than 5 ng/ml. The sample sizes were smaller at prostate specific antigen levels greater than 5 ng/ml so the results are harder to interpret. CONCLUSIONS: Bone scans can be confidently eliminated in the followup of patients with early prostate cancer after standard care of those with prostate specific antigen levels less than 5 ng/ml. This level can be increased to 20 ng/ml with caution in those patients treated with watchful waiting.

Perceptual magnet and phoneme boundary effects in speech perception: do they arise from a common mechanism?

The question of whether sensitivity peaks at vowel boundaries (i.e., phoneme boundary effects) and sensitivity minima near excellent category exemplars (i.e., perceptual magnet effects) stem from the same stage of perceptual processing was examined in two experiments. In Experiment 1, participants gave phoneme identification and goodness ratings for 13 synthesized English /i/ and /e/ vowels. In Experiment 2, participants discriminated pairs of these vowels. Either the listeners discriminated the entire range of stimuli within each block of trials, or the range within each block was restricted to a single stimulus pair. In addition, listeners discriminated either one-step or two-step intervals along the stimulus series. The results demonstrated that sensitivity peaks at vowel boundaries were more influenced by stimulus range than were perceptual magnet effects; peaks in sensitivity near the /i/-/e/ boundary were reduced with restricted stimulus ranges and one-step intervals, but minima in discrimination near the best exemplars of /i/ were present in all conditions.

Measuring the perceptual magnet effect in the perception of /i/ by German listeners.

In a study of the internal category structure of the vowel /i/, Kuhl found a "perceptual magnet effect": Discrimination sensitivity was poorer for category instances that were acoustically similar to the category prototype than it was for category instances that were not. The typicality of category exemplars was determined by goodness judgments and was found to correlate with the acoustics of average production. Analysis and interpretation of discrimination performance relied on two important assumptions: that listeners perceived all stimuli presented as exemplars of the same vowel category and that, apart from the influence of phonetic coding, discrimination sensitivity was the same across the investigated part of the vowel space. In the present study, it is shown that production and perception estimates of the category prototype may diverge, possibly because listeners seem to prefer hyperarticulated variants of vowel categories. An approach towards measurement of intra-category discrimination minima is put forward and tested that protects against intercategory confounds and avoids the isosensitivity assumption.

Name that tune: identifying popular recordings from brief excerpts.

We tested listeners' ability to identify brief excerpts from popular recordings. Listeners were required to match 200- or 100-msec excerpts with the song titles and artists. Performance was well above chance levels for 200-msec excerpts and poorer but still better than chance for 100-msec excerpts. Performance fell to chance levels when dynamic (time-varying) information was disrupted by playing the 100-msec excerpts backward and when high-frequency information was omitted from the 100-msec excerpts; performance was unaffected by the removal of low-frequency information. In sum, successful identification required the presence of dynamic, high-frequency spectral information.

Prostate cancer in Denmark. Incidence, morbidity and mortality.

Prostate cancer incidence and mortality rates in Denmark are reviewed for a 50-year period from 1943 to 1992. The prostate cancer incidence rate nearly tripled and prostate cancer mortality rate increased during this period. Until recently in Denmark the routine management of prostate cancer has been by deferred hormonal therapy. Morbidity and mortality associated with prostate cancer are analysed in a group of 1459 patients aged 55-74 years, who were diagnosed as having clinically localized prostate cancer in the 5-year period 1983 to 1987. In this group of patients prostate cancer is demonstrated to cause significant morbidity. Furthermore, the patients suffered significant excess mortality and loss of life expectancy.

[Use of prostate specific antigen. A review]. / Anvendelse af prostataspecifikt antigen. En oversigt.

Since it was first introduced, measurement of prostate specific antigen has gained increasing interest, and prostate specific antigen is regarded as being the best tumour marker available. The antigen lacks cancer specificity, limiting the usefulness in early diagnosis, The use of prostate specific antigen in early diagnosis, staging, and in monitoring patients with prostate cancer is reviewed.

Influences of phonetic identification and category goodness on American listeners' perception of /r/ and /l/.

Recent experiments have demonstrated that category goodness influences the perception of vowels [Iverson and Kuhl, J. Acoust. Soc. Am. 97, 553-562 (1995)]; listeners show a perceptual magnet effect characterized by shrunken perceptual distances near excellent exemplars of vowel categories and stretched distances near poor exemplars. The present study extends this investigation by examining the relative influence of phonetic identification and category goodness on the perception of American English /r/ and /l/. Eighteen /ra/ and /la/ tokens were synthesized by varying F2 and F3 frequencies. Adult listeners identified and rated the goodness of individual stimuli, and rated the similarity of stimulus pairs. Multidimensional scaling analyses revealed that the perceptual space was shrunk near the best exemplars of each category and stretched near the category boundary. In addition, individual differences in /r/ identification corresponded to the degree of shrinking near the best exemplars of the /r/ category. The results demonstrate that category goodness and phonetic identification both contribute to the perception of /r/ and /l/.

Auditory stream segregation by musical timbre: effects of static and dynamic acoustic attributes.

Two experiments examined the influence of timbre on auditory stream segregation. In experiment 1, listeners heard sequences of orchestral tones equated for pitch and loudness, and they rated how strongly the instruments segregated. Multidimensional scaling analyses of these ratings revealed that segregation was based on the static and dynamic acoustic attributes that influenced similarity judgements in a previous experiment (P Iverson & CL Krumhansl, 1993). In Experiment 2, listeners heard interleaved melodies and tried to recognize the melodies played by a target timbre. The results extended the findings of Experiment 1 to tones varying pitch. Auditory stream segregation appears to be influenced by gross differences in static spectra and by dynamic attributes, including attack duration and spectral flux. These findings support a gestalt explanation of stream segregation and provide evidence against peripheral channel model.

Mapping the perceptual magnet effect for speech using signal detection theory and multidimensional scaling.

Recent experiments have demonstrated that the category goodness of speech sounds strongly influences perception in both adult and infants [Kuhl, Percept. Psychophys. 50, 93-107 (1991); Kuhl et al., Science 255, 606-608 (1992)]. Stimuli judged as exceptionally good instances of phonetic categories (prototypes) make neighboring tokens in the vowel space seem more similar, exhibiting a perceptual magnet effect. Three experiments further examined the perceptual magnet effect in adults. Experiment 1 collected goodness and identification judgments for 13 variants of the vowel /i/. Experiment 2 used signal detection theory to assess the discrimination of these tokens using a bias-free measure (d'). Experiment 3 employed multidimensional scaling (MDS) to geometrically model the distortion of the perceptual space due to the magnet effect. The results demonstrated a strong relationship between category goodness and discrimination. Vowel tokens receiving high goodness ratings in experiment 1 were more difficult to discriminate in experiment 2 and were more tightly clustered in the MDS solutions of experiment 3. These findings support the existence of a perceptual magnet effect, and may help explain some aspects of first language learning in infants and second language learning in adults.

Isolating the dynamic attributes of musical timbre.

Three experiments examined the dynamic attributes of timbre by evaluating the role of onsets in similarity judgments. In separate experiments, subjects heard complete orchestral instrument tones, the onsets of those tones, and tones with the onsets removed ("remainders"). Ratings for complete tones corresponded to those for onsets, indicating that the salient acoustic attributes for complete tones are present at the onset. Ratings for complete tones also corresponded to those for remainders, indicating that the salient attributes for complete tones are present also in the absence of onsets. Subsequent acoustic analyses demonstrated that this pattern of similarity was due to the centroid frequencies and amplitude envelopes of the tones. The results indicate that the dynamic attributes of timbre are not only present at the onset, but also throughout, and that multiple acoustic attributes may contribute to the same perceptual dimensions.

Bilateral coronoid hyperplasia: an important cause of restricted mandibular motion.

The diagnosis of coronoid hyperplasia relies on clinical history as well as physical findings. A history of slowly progressive limitation of motion should heighten one's index of suspicion that the limitation may not necessarily be due to a simple muscular disorder or a disorder involving the temporomandibular joint per se. Absence of a history of internal derangement is an important consideration. Simple screening films should be employed prior to subjecting the patient to more detailed studies. A panogram and Waters' projection of the mid-face are quite diagnostic. Utilization of tomography, arthrography, and magnetic resonance imaging should be considered only after appropriate screening films have been reviewed.

Perceptual interactions between musical pitch and timbre.

These experiments examined perceptual interactions between musical pitch and timbre. Experiment 1, through the use of the Garner classification tasks, found that pitch and timbre of isolated tones interact. Classification times showed interference from uncorrelated variation in the irrelevant attribute and facilitation from correlated variation; the effects were symmetrical. Experiments 2 and 3 examined how musical pitch and timbre function in longer sequences. In recognition memory tasks, a target tone always appeared in a fixed position in the sequences, and listeners were instructed to attend to either its pitch or its timbre. For successive tones, no interactions between timbre and pitch were found. That is, changing the pitches of context tones did not affect timbre recognition, and vice versa. The tendency to perceive pitch in relation to other context pitches was strong and unaffected by whether timbre was constant or varying. In contrast, the relative perception of timbre was weak and was found only when pitch was constant. These results suggest that timbre is perceived more in absolute than in relative terms. Perceptual implications for creating patterns in music with timbre variations are discussed.

Interaction of lipoprotein lipase with heparin.

The hydrolysis of triglyceride-rich plasma lipoproteins is initiated by lipoprotein lipase (LPL) located at the luminal surface of endothelial cells. We previously reported that LPL binds to cultured endothelial cells with a Km of 2.7 x 10(-7) M and that this binding is inhibited by heparinase, heparin, or heparan sulfate. We and others recently isolated LPL cDNAs from various animals. The deduced amino acid sequence from cDNA sequence is highly conserved among animal species. The structural analysis revealed two regions rich in basic amino acid residues at the carboxyl-terminal region that may interact with the anionic heparin-like molecules. Amino acid residues 292 to 300 of bovine LPL are extremely similar to the reported heparin binding sites on apolipoproteins B-100 (amino acid residues 3359-3367) and E (amino acid residues 142-150).

Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo.

Previous data suggest that apolipoprotein (apo) CIII may inhibit both triglyceride hydrolysis by lipoprotein lipase (LPL) and apo E-mediated uptake of triglyceride-rich lipoproteins by the liver. We studied apo B metabolism in very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL) in two sisters with apo CIII-apo AI deficiency. The subjects had reduced levels of VLDL triglyceride, normal LDL cholesterol, and near absence of high density lipoprotein (HDL) cholesterol. Compartmental analysis of the kinetics of apo B metabolism after injection of 125I-VLDL and 131I-LDL revealed fractional catabolic rates (FCR) for VLDL apo B that were six to seven times faster than normal. Simultaneous injection of [3H]glycerol demonstrated rapid catabolism of VLDL triglyceride. VLDL apo B was rapidly and efficiently converted to IDL and LDL. The FCR for LDL apo B was normal. In vitro experiments indicated that, although sera from the apo CIII-apo-AI deficient patients were able to normally activate purified LPL, increasing volumes of these sera did not result in the progressive inhibition of LPL activity demonstrable with normal sera. Addition of purified apo CIII to the deficient sera resulted in 20-50% reductions in maximal LPL activity compared with levels of activity attained with the same volumes of the native, deficient sera. These in vitro studies, together with the in vivo results, indicate that in normal subjects apo CIII can inhibit the catabolism of triglyceride-rich lipoproteins by lipoprotein lipase.

Plasma apolipoprotein secretion by human monocyte-derived macrophages.

Apolipoprotein E has been demonstrated to be a major secretory protein of human monocyte macrophages. The synthesis of the other plasma apolipoproteins by these cells has not been documented. Human monocyte macrophages cultured for 17-76 days were preincubated for 24 h in RPMI 1640/0.2% bovine serum albumin with or without malondialdehyde-LDL (100 micrograms/ml), followed by an additional 24 h incubation in RPMI 1640/0.2% bovine serum albumin. The media from the two incubation periods were analyzed for apolipoproteins A-I, B, C-II, C-III and E by specific radioimmunoassays. No apolipoprotein B mass was detected with a specific radioimmunoassay capable of detecting 10 ng apolipoprotein B. No apolipoproteins A-I, C-II or C-III mass was detected, even though the radioimmunoassays for these apolipoproteins were as sensitive as that for apolipoprotein E (detection limit of 0.2 ng). In contrast, significant levels of macrophage-secreted apolipoprotein E were quantified. Baseline apolipoprotein E production ranged from 0.64 to 2.82 micrograms/mg cell protein per 24 h. Preincubation in the presence of malondialdehyde-LDL (100 micrograms/ml) stimulated a 1.6-3.0-fold increase in apolipoprotein E secretion. The identification of the immunoreactive material as apolipoprotein E was confirmed by labelling the cells with [35S]methionine, followed by fractionation of the 35S-labelled secretory products by anti-apolipoprotein E affinity chromatography and SDS-gel electrophoresis. We thus report the absence of synthesis of apolipoproteins A-I, B, C-II and C-III by cultured human monocyte macrophages. These cells, however, can synthesize microgram levels of apolipoprotein E on a per mg protein basis.

Apo E-mediated uptake and degradation of normal very low density lipoproteins by human monocyte/macrophages: a saturable pathway distinct from the LDL receptor.

Normal human fasting very low density lipoproteins (n-VLDL; d less than 1.006 g/ml) were demonstrated to be taken up and degraded by human monocyte-macrophages via a saturable process distinct from the previously described LDL and scavenger receptors. Through the use of apolipoprotein-phospholipid complexes, apolipoprotein E (apoE) was identified as the ligand mediating recognition of n-VLDL by this receptor.