Studies of prosody perception by cochlear implant patients

Prosodic information is conveyed to normally-hearing listeners by variations in acoustic fundamental frequency, amplitude envelope, and duration of speech segments. This study measured cochlear implant patients' sensitivity to these parameters in electrically coded speech. The psychophysical discrimination of electric parameters used to code prosodic information, were examined, together with prosody perception using speech processing strategies which modified the contributions of these parameters. Patients were implanted with the Cochlear Limited prosthesis and used the MPEAK speech processing strategy. In the psychophysical studies, difference limens were measured for steady-state and time-varying stimuli, of different pulse rates and pulse durations, over a series of different stimulus durations. These limens were obtained using an adaptive procedure which converged on the 50 per cent correct point. In the prosody perception studies, performance was measured for the MPEAK strategy and for strategies which modified the contributions of pulse rate and pulse duration. Data were collected for five tests of prosodic contrasts. Difference limens for steady-state pulse rates were larger at higher rates (17 per cent at 400 pulses/s) than at lower rates (6 per cent at 100 pulses/s). For some patients, limens for the time-varying pulse rates were larger than those for the steady-state pulse rates while for the other patients, the limens were similar. Difference limens for pulse duration were 0.3 dB, corresponding to 4 per cent of the dynamic range, for steady-state stimuli and doubled in size for the time-varying stimuli. Prosody perception performance was generally poorer for the modified strategies than for the MPEAK strategy, suggesting that the removal of information coded by pulse rate and pulse duration reduced the perception of prosodic contrasts.     

Targeting the receptor-Gq interface to inhibit in vivo pressure overload myocardial hypertrophy

Hormones and neurotransmitters may mediate common responses through receptors that couple to the same class of heterotrimeric guanine nucleotide-binding (G) protein. For example, several receptors that couple to Gq class proteins can induce cardiomyocyte hypertrophy. Class-specific inhibition of Gq-mediated signaling was produced in the hearts of transgenic mice by targeted expression of a carboxyl-terminal peptide of the alpha subunit Galphaq. When pressure overload was surgically induced, the transgenic mice developed significantly less ventricular hypertrophy than control animals. The data demonstrate the role of myocardial Gq in the initiation of myocardial hypertrophy and indicate a possible strategy for preventing pathophysiological signaling by simultaneously blocking multiple receptors coupled to Gq.     

MR imaging of symptomatic osteochondromas with pathological correlation

Presentation of antigenic peptides by major histocompatibility complex (MHC) class I molecules depends on translocation of cytosolic peptides into the endoplasmic reticulum (ER) by transporters associated with antigen processing (TAP). Peptide transport by TAP is thought to include at least two steps: initial binding of peptide to TAP, and its subsequent translocation requiring ATP hydrolysis. These events can be monitored in peptide binding and transport assays. Previous studies have shown that the efficiency of peptide transport by human, mouse and rat transporters varies according to the C-terminals of peptide substrates in an allele and species-specific manner. However, it has not been clear during which step of peptide interaction with TAP selection occurs. We used an assay monitoring the peptide binding step to study the binding affinity of a library of 199 peptides for human TAP and the two major allelic rat TAP complexes. We observed a dominant influence of the C-terminus on peptide binding affinity for all transporters, and highly restrictive selection of peptides with aliphatic and aromatic C-terminals by rat TAP1/TAP2u complexes. The selectivity of peptide binding to rat TAP complexes is in full accordance with published data on selective peptide transport and on control of antigen presentation by rat TAP. These results strongly suggest that (i) peptide selection by TAP occurs exclusively in the initial binding step; (ii) all factors involved in peptide selection by TAP are present in insect cells.     

Genetic transformation of germinated conidia of the thermophilic fungus Humicola grisea var. thermoidea to hygromycin B resistance

Dihydrotestosterone decreased alcohol dehydrogenase (ADH) activity and enzyme-protein in rat hepatocytes in culture. This effect was observed after the hepatocytes had been exposed to dihydrotestosterone for 3 days at concentrations of 0.5 micromol/L or higher. Dihydrotestosterone did not decrease alcohol dehydrogenase messenger RNA (mRNA) but, rather, resulted in small increases in ADH mRNA after 3 days of exposure. To further determine the mechanism for the effects of dihydrotestosterone in decreasing the enzyme, the turnover of ADH was determined after incorporation of [3H]-leucine into the enzyme protein. Dihydrotestosterone did not alter the initial 2-hour incorporation of [3H]-leucine into the enzyme protein. Dihydrotestosterone, however, resulted in an increase in the fractional rate of degradation (Kd) of the enzyme from 0.12 +/- 0.013 to 0.23 +/- 0.004 per hour (P < .001) accompanied by a much smaller increase in the fractional rate of synthesis (Ks) from 0.12 +/- 0.028 to 0.17 +/- 0.031 per hour (P > .05). Hence, the mechanism for the fall in ADH in the presence of dihydrotestosterone is an increase in enzyme degradation which is not accompanied by a sufficient increase in enzyme synthesis.     

Antibody to epitope tag induces internalization of human muscarinic subtype 1 receptor

The degree to which a startle response to a loud noise is inhibited by a weak prestimulus is an operational measure of sensorimotor gating. Prepulse inhibition (PPI) can be measured across species and is reduced in schizophrenia patients and dopamine (DA)-activated rats. The ability of DA antagonists to restore PPI in apomorphine (APO)-treated rats correlates highly with their clinical antipsychotic potency. We compared the ability of systemic- vs. intracerebrally (i.c.)-administered haloperidol (HAL) to restore PPI in APO-treated rats. Consistent with previous studies, systemic administration of HAL completely restored PPI in rats treated with APO (0.5 mg/kg s.c.), with an ED50 of approximately 0.02 mg/kg. In an otherwise identical paradigm, HAL failed to fully restore PPI after infusion into either the nucleus accumbens (NACcore or NACshell), NACcore + caudate nucleus (CN), ventral subiculum (VS), medial prefrontal cortex (MPFC), or ventral tegmentum (VTA). A subtotal, but statistically significant restoration of PPI was achieved after HAL infusion into all regions, except the NACshell. Statistically significant effects of i.c. HAL tended to be observed at doses that were only approximately 5-10-fold lower than those at which significant effects were observed after systemic administration. The results suggest that systemically administered HAL may restore PPI in APO-treated rats through its action distributed throughout multiple levels of PPI-regulatory circuitry.     

Limited value of preoperative cervical vascular imaging in patients with velocardiofacial syndrome

The purpose of this two-part study was to evaluate the safety of surgical management of speech production disorders in patients with velocardiofacial syndrome without preoperative cervical vascular imaging studies. Anomalous internal carotid arteries have been shown to be a frequent feature of velocardiofacial syndrome. These vessels pose a potential risk for hemorrhage during velopharyngeal narrowing procedures. Magnetic resonance angiography, and other forms of cervical vascular imaging studies such as computerized tomography, have been advocated as aids to surgery by defining the preoperative vascular anatomy. However, it remains unclear whether these studies alter either the conduct or outcome of operations on the velopharynx. In the first part of this study, we reviewed the charts and videonasendoscopic evaluations of 39 consecutive patients with confirmed or suspected velocardiofacial syndrome who underwent sphincter pharyngoplasty or pharyngeal flap from 1978 to 1996. The charts were reviewed to determine (1) the frequency of identification of abnormal pharyngeal pulsations; (2) whether such pulsations affected the conduct of the operative procedure; and (3) whether the presence of pulsations affected surgical morbidity and/or surgical outcome. None of the patients underwent any type of cervical vascular imaging study. In the second part of this study, we surveyed plastic surgeons with numerous years of experience participating on cleft-craniofacial teams, to ascertain practice patterns relating to the management of patients with velocardiofacial syndrome. The questions related specifically to the surgeons' behavior in relation to angiography and their awareness of any cases of surgical morbidity related to the cervical vascular system in patients with velocardiofacial syndrome. We were interested in discerning both how commonly this situation arises clinically and the distribution of the various types of operative procedures in common use. Of our 39 patients, 10 patients (26 percent) had detectable pulsations on preoperative nasendoscopy. Of these, five patients underwent sphincter pharyngoplasty and five underwent pharyngeal flap procedures. Preoperative instrumental and intraoperative clinical assessment of pulsatile vessels allowed velopharyngeal reconstruction in all patients without surgical morbidity. Results of the questionnaire indicated that most cleft surgeons do not routinely order cervical vascular imaging studies for all of their patients with velocardiofacial syndrome. About half of the respondents indicated that their operative approach was influenced by information obtained from angiographic studies. None of the surgeons queried were aware of any cases of surgical morbidity related to the cervical vascular system in patients with velocardiofacial syndrome. Nearly 50 percent of surgeons use pharyngeal flap procedures most frequently, whereas 22 percent of surgeons use sphincter pharyngoplasty most frequently. Results of this study support the safety of sphincter pharyngoplasty or pharyngeal flap procedures in patients with velocardiofacial syndrome without preparatory angiography. These procedures can be performed safely, even in patients having aberrant velopharyngeal pulsations. Given the market cost of magnetic resonance angiography ($1600), one must question the cost-efficacy of magnetic resonance angiography for routine use in the velocardiofacial syndrome population.     

Serum leptin concentration and insulin sensitivity in men with abdominal obesity

Papillary immature metaplasia (PIM) of the cervix (immature condyloma) is a variant of low-grade squamous intraepithelial lesions (LSIL). It is frequently associated with human papillomavirus (HPV) types 6 and 11. The purpose of this study was to characterize the cytologic changes associated with this lesion. We analyzed 10 cases of PIM from our files and reviewed the Papanicolaou smears taken proximate to the time of the biopsy. Four cases had either reactive epithelial changes (2 cases) or cytologic findings typical of low-grade SIL, with koilocytosis (2 cases). Six cases displayed a spectrum of metaplastic cells with varying maturation that ranged from atypical reactive cells to atypical immature metaplastic cells. Binucleation was common. Some cells exhibited features characteristic of SIL, although the degree of nuclear atypia generally was less than that associated with high-grade SIL. Papanicolaou smears from all cases were interpreted as atypical (ASCUS) metaplasia or low-grade SIL. Follow-up biopsy in one case revealed a PIM in association with a high-grade SIL, the latter undiagnosed by smear alone. PIM is a distinct histologic entity that can present with a spectrum of cytologic findings. Its recognition histologically can resolve some cytologic/histologic discrepancies. Confusion with an immature HSIL or atypical immature metaplasia can occur in some instances and the diagnosis of PIM by cytology alone is not recommended, unless the diagnosis is qualified.     

Desensitization of beta3-adrenergic receptor-stimulated adenylyl cyclase activity and lipolysis in rats

The beta3-adrenergic receptor is an integral membrane protein consisting of seven transmembrane domains. Unlike the beta1 and beta2 receptors, this subtype lacks the consensus phosphorylation sites required for desensitization by serine kinases. Using the rodent specific beta3 agonist BRL 35135, our initial data indicated that beta3 receptor-mediated glycerol levels progressively decreased following daily oral doses of 5 mg/kg. Therefore, we initiated studies designed to delineate the possible mechanism(s) for this decreased response. Within 3 hours following a single oral dose of BRL 35135, serum glycerol levels and UCP (uncoupling protein) RNA levels were significantly increased whereas beta3 RNA levels were significantly decreased. Rats were dosed daily for 5 days with either vehicle or BRL 35135 (5 mg/kg, p.o.) and blood samples were collected for glycerol analysis. Adipose tissue was excised for lipolysis and adenyl cyclase measurements. In addition, UCP and beta3 receptor RNA levels were assessed. No effect on adipocyte BRL 37344-stimulated adenylyl cyclase activity was observed 3 hours following the initial dose of BRL 35135. Although a slight decrease (approximately 25%) in adenylyl cyclase activity could be observed 24 hours following the initial dose, it wasn't until day 4 of dosing that a significant decrease (50%) was observed. In contrast, beta3- stimulated lipolysis in adipocytes from BRL 35135-treated rats was decreased 85% within 24 hours and this decrease persisted through four days of treatment. These data indicate that the lipolytic response to beta3 receptor activation is decreased after only a single oral dose of BRL 35135, whereas receptor-mediated adenylyl cyclase activation, although initially unaffected, also desensitizes by day four of treatment.