Initial noun meanings do not differentiate into object categories: An experimental approach to Werner and Kaplan's hypothesis.

During the initial stage of language development, nouns corresponding to "object categories" are known to be acquired earlier than other parts of speech, including verbs. However, it is unclear whether the semantic content of words is the same for toddlers who have just begun to learn them and adult speakers. This preliminary study experimentally investigated the theoretical hypothesis of Werner and Kaplan, which posited that the initial meanings of noun-like words do not differentiate into specific categories of objects themselves but rather refer to holistic event categories. Toddlers aged 19-35 months (N = 36) were prompted to select one of two juxtaposed video stimuli (e.g., "putting shoes on" vs. "rubbing two baskets" in the match condition, "putting baskets on" vs. "rubbing shoes" in the mismatch condition) using questions about noun-like words (e.g., "Which is shoes?"). Statistical modeling demonstrated that the meanings of noun-like words for toddlers under 21 months of age or with a vocabulary size of less than 140 words were deeply influenced by conventional actions related to the objects (e.g., "putting shoes on"), whereas they subsequently differentiated into specific object categories (e.g., "shoes" alone), becoming "true nouns." These findings support Werner and Kaplan's hypothesis and provide the first experimental evidence for the theoretical and observational assumptions that early words are not easily classified into parts of speech only by their vocables (e.g., nouns, verbs). We discuss the flexibility of vocable-meaning connections during early language development by proposing the "semantic pluripotency hypothesis."

Pulmonary delivery of peptide YY for food intake suppression and reduced body weight gain in rats.

AIMS: Peptide YY (PYY) is an endogenous anorectic gut-secreted peptide that has been shown to suppress appetite in animals and humans, when given by injection. This study tested if needle-free pulmonary delivery of PYY enables food intake suppression and reduced body weight gain in rats. The PYY pharmacokinetics and effects on brain neuropeptide levels were also examined. METHODS: Rats received single or once-daily 7-day pulmonary administration of saline or PYYs. Food intake and body weight gain were monitored to study the effects of different doses (0.08-0.90 mg/kg) of PYY3-36, PYY1-36 and PYY13-36. Plasma PYY pharmacokinetics were determined via enzyme-linked immunosorbent assay. Changes in orexigenic neuropeptide Y (NPY) and c-Fos protein levels in the hypothalamus arcuate nucleus (ARC) were measured by immunofluorescence microscopy. RESULTS: PYY3-36 caused dose-dependent and 4- to 6-h food intake suppression following pulmonary delivery. At 0.80 mg/kg, the effect was significant with 35.1 ± 5.7 and 19.7 ± 4.2% suppression at 4 and 6 h, respectively. Repeated administration for 7 days reduced cumulative body weight gain by 39.4 ± 11.0%. PYY1-36, but not PYY13-36, was equipotent to PYY3-36 in food intake suppression. The plasma PYY concentration reached its peak at 10 min following pulmonary delivery with 12-14% of bioavailability. Increased c-Fos and reduced NPY expressions were observed in the hypothalamus ARC, consistent with the magnitude of food intake suppression by each of the PYYs. CONCLUSIONS: Pulmonary delivery of PYY enabled significant 4- to 6-h food intake suppression via 12-14% of lung absorption and hypothalamic ARC interaction, leading to reduced body weight gain in rats.

Odontogenic chronic rhinosinusitis patients undergoing tooth extraction: oral surgeon and otolaryngologist viewpoints and appropriate management.

OBJECTIVE: This study aimed to propose appropriate management for odontogenic chronic rhinosinusitis. METHOD: Thirty-one adult patients with odontogenic chronic rhinosinusitis undergoing maxillary extraction were retrospectively analysed. Patients with (n = 21) and without (n = 10) oroantral fistula on computed tomography were classified. Functional endoscopic sinus surgery was performed when sinusitis did not improve after extraction. The critical indicators for surgical requirement in the management of odontogenic chronic rhinosinusitis were analysed. RESULTS: Sinusitis significantly improved after extraction in both groups. Patients without oroantral fistula had significantly more severe remnant sinusitis than those with oroantral fistula after extraction on computed tomography (p = 0.0037). The requirement for functional endoscopic sinus surgery was statistically significant for patients without orofacial fistula over those with orofacial fistula (p < 0.0001). The surgical improvement ratio was 93 per cent. CONCLUSION: The absence of oroantral fistula and severe sinusitis can be critical indicators for the requirement of functional endoscopic sinus surgery after extraction in the management of odontogenic chronic rhinosinusitis.

Predictors of disease progression after endoscopic sinus surgery in patients with chronic rhinosinusitis.

OBJECTIVE: This study aimed to determine the predictors of disease progression after functional endoscopic sinus surgery in patients with chronic rhinosinusitis. METHOD: A total of 281 adult chronic rhinosinusitis patients who underwent primary bilateral functional endoscopic sinus surgery between 2007 and 2017 and had at least 12 months of follow-up endoscopic evaluation were examined. Patients were divided into eosinophilic (n = 205) and non-eosinophilic chronic rhinosinusitis groups (n = 76). In order to determine adverse factors, post-operative endoscopic appearance scores were analysed in relation to the pre- and intra-operative findings using multiple regression analyses. RESULTS: The post-operative course of eosinophilic cases deteriorated over time, like the early period for non-eosinophilic cases. Frontal sinus polyps recurred early in eosinophilic chronic rhinosinusitis. Multivariate analyses indicated young adulthood, asthma, high computed tomography score and frontal sinus polyps as significant adverse predictors. CONCLUSION: Early, appropriate estimation of sinonasal conditions appears to be crucial for successful surgical management of chronic rhinosinusitis.

Nizatidine enhances salivary secretion in patients with dry mouth.

OBJECTIVE: It was reported that salivary secretion increased in 30 volunteers with administered nizatidine. The aim of the present study was to investigate whether or not nizatidine enhances salivary secretion and improves the function of salivary glands in patients with dry mouth. METHODS: Both basal and stimulated salivary secretions were measured before and after the administration of nizatidine for a month in 18 healthy adult volunteers and 38 patients with dry mouth. In 6/38 patients, salivary gland scintigraphy was performed. RESULTS: After the administration of nizatidine for a month, salivary secretions significantly increased in the control and dry mouth patient groups compared to the pretreatment baseline. In addition, 25 of 38 dry mouth patients showed subjective improvements of oral dryness. In 3/4 patients, the function of salivary glands was improved on salivary gland scintigraphy. CONCLUSION: Nizatidine may reactivate salivary gland cells and be useful in the treatment of patients with dry month.

Statistical modelling of knee valgus during a continuous jump test.

Landing with the knee in a valgus position is recognized as a risk factor for anterior cruciate ligament (ACL) injury. Using linear and non-linear regression analyses, the purpose of this study was to examine the correlation between two-dimensional (2D) knee valgus and three-dimensional (3D) knee kinematics measured during a jump landing task. Twenty-eight female collegiate athletes participated. All participants were required to perform a continuous jump test. The average maximum angles of abduction and internal tibial rotation during landing were measured using the Point Cluster Technique. Average peak knee valgus angle was measured using a 2D approach. Linear and non-linear regression analyses between 2D valgus and 3D knee abduction, and between 2D valgus and 3D internal tibial rotation, were performed. The R2 value between 2D valgus and 3D knee abduction was significantly different from zero and had a moderate correlation for all models, whereas the R2 value between 2D valgus and 3D internal tibial rotation was not significantly different from zero. The 2D approach could be used to screen a specific group of individuals for risk of ACL injury; however, using frontal plane 2D analysis of valgus motion to evaluate internal tibial rotation is not advised.

Post-operative course prediction during endoscopic sinus surgery in patients with chronic rhinosinusitis.

OBJECTIVE: This study aimed to analyse findings of functional endoscopic sinus surgery to estimate the post-operative course of patients with chronic rhinosinusitis. METHODS: From 2007 to 2015, 291 adult patients with bilateral chronic rhinosinusitis, divided into eosinophilic chronic rhinosinusitis (n = 210) and non-eosinophilic chronic rhinosinusitis (n = 81) groups, who underwent primary functional endoscopic sinus surgery were enrolled. Functional endoscopic sinus surgery findings, scored as operating score, were analysed in relation to pre-operative olfactory recognition threshold and sinonasal computed tomography imaging score, as well as post-operative endoscopic appearance. RESULTS: Operating scores in eosinophilic chronic rhinosinusitis were significantly worse than those in non-eosinophilic chronic rhinosinusitis. The anterior ethmoid sinus and superior meatus were predominantly inflamed. Operating score significantly correlated with pre-operative olfaction recognition threshold, computed tomography score and pre-operative endoscopic appearance score. In eosinophilic chronic rhinosinusitis, higher operating scores were related to post-operative deterioration of endoscopic appearance score. CONCLUSION: The operating score reflects the course following functional endoscopic sinus surgery. Patients with more severe operative findings require longer post-operative treatment.

Relationship between Eustachian tube dysfunction and otitis media with effusion in radiotherapy patients.

OBJECTIVE: This study evaluated the relationship between radiation and Eustachian tube dysfunction, and examined the radiation dose required to induce otitis media with effusion. METHODS: The function of 36 Eustachian tubes in 18 patients with head and neck cancer were examined sonotubometrically before, during, and 1, 2 and 3 months after, intensity-modulated radiotherapy. Patients with an increase of 5 dB or less in sound pressure level (dB) during swallowing were categorised as being in the dysfunction group. Additionally, radiation dose distributions were assessed in all Eustachian tubes using three dose-volume histogram parameters. RESULTS: Twenty-two of 25 normally functioning Eustachian tubes before radiotherapy (88.0 per cent) shifted to the dysfunction group after therapy. All ears that developed otitis media with effusion belonged to the dysfunction group. The radiation dose threshold evaluation revealed that ears with otitis media with effusion received significantly higher doses to the Eustachian tubes. CONCLUSION: The results indicate a relationship between radiation dose and Eustachian tube dysfunction and otitis media with effusion.

Influence of opacification in the frontal recess on frontal sinusitis.

OBJECTIVES: This study aimed to radiologically evaluate the influence of inflammatory changes in frontal recess cells on frontal sinusitis. METHODS: A total of 93 patients (186 sides) who underwent primary sinonasal surgery at Hyogo College of Medicine were enrolled in 2015 and 2016. Opacification of agger nasi, fronto-ethmoidal, ethmoid bulla, suprabullar and frontal bulla cells was determined by pre-operative computed tomography and its influence on frontal sinusitis was investigated. RESULTS: In all, 42 per cent of 186 sides were affected by frontal sinusitis. Agger nasi, ethmoid bulla, fronto-ethmoidal, suprabullar and frontal bulla cells were identified in 99 per cent, 100 per cent, 38 per cent, 69 per cent, and 16 per cent of sides, respectively. The presence of frontal recess cells and frontal ostium size did not significantly influence frontal sinusitis development. However, opacification of agger nasi, type 1 fronto-ethmoidal and suprabullar cells significantly influenced frontal sinusitis development. CONCLUSION: Frontal sinusitis is caused by inflammatory changes in frontal recess cells.

Expression of CD44 variant isoforms, CD44v3 and CD44v6, are associated with prognosis in nasopharyngeal carcinoma.

OBJECTIVE: The clinical and prognostic significance of CD44 variant isoform expression in nasopharyngeal carcinoma is not well known. This study aimed to clarify whether CD44 variant isoform expression serves as a prognostic factor in nasopharyngeal carcinoma. METHODS: Forty-two nasopharyngeal carcinoma patients, who underwent concurrent chemoradiotherapy as the initial treatment, were the subjects of investigation. Expression of CD44 variant isoforms, CD44v3, CD44v4, CD44v5, CD44v6 and CD44v7, in nasopharyngeal carcinoma was assessed in relation to concurrent chemoradiotherapy resistance and disease-specific survival of the patients. RESULTS AND CONCLUSION: The patients with CD44v6 high expression showed a clinically incomplete response to concurrent chemoradiotherapy at the primary site. The disease-specific survival rate was lower in patients with high expression of CD44v3 than in those with low expression. These results suggest that analysis of CD44v6 and CD44v3 expression is useful in estimating prognosis and determining effective treatment strategies in nasopharyngeal carcinoma.

A code for behavioral inhibition on the basis of color, but not motion, in ventrolateral prefrontal cortex of macaque monkey.

To examine the neural mechanism for behavioral inhibition, we recorded single-cell activity in macaque ventrolateral prefrontal cortex, which is known to receive visual information directly from the inferotemporal cortex. In response to a moving random pattern of colored dots, monkeys had to make a go or no-go response. In the color condition, green indicated go, whereas red indicated no-go, regardless of the motion direction; in the motion condition, upward indicated go, whereas downward indicated no-go, regardless of the color. Approximately one-half of the visual cells were go/no-go differential. A majority of these cells (64/73) showed differential activity only in the color condition; they responded nondifferentially in the motion condition, although the same set of stimuli was used. We classified these cells as "go type" (n = 41) and "no-go type" (n = 23) depending on the color for which they showed a stronger response. Interestingly, in both types of cells, the differential effects were observed only for the no-go-indicating color. Compared with the nondifferential responses in the motion condition, go-type cells in the color condition showed weaker responses to the no-go-indicating color, whereas their responses to the go-indicating color were similar; in contrast, no-go type cells showed stronger responses to the no-go-indicating color, whereas their responses to the go-indicating color were similar. Both types of cells did not show any activity change during the actual execution of the go or no-go response. These results suggest that neurons in ventrolateral prefrontal cortex contribute to stimulus-response association in complex task situations by inhibiting behavioral responses on the basis of visual information from the ventral stream.

Syntheses of C-peptides and human proinsulin.

Syntheses of human, dog, rat, and duck C-peptides and their analogues and preliminary results on the total synthesis of human proinsulin are described. In the syntheses of the C-peptides, chain elongation was performed exclusively by the azide-fragment condensation method in solution. The synthetic human, dog, rat, and duck C-peptides and their analogues were proved to be homogeneous by several analytic means. With these synthetic peptides, radioimmunoassay systems for dog, rat, and duck C-peptides were developed. For the total synthesis of human proinsulin, 10 protected peptide hydrazides were prepared, and the linearly protected hexaoctacontapeptide having the proposed sequence of human proinsulin was constructed by the azide-fragment condensation method in solution starting from the C-terminal undecapeptide (HP 75-86). After deblocking of the alpha-amino protection, the partially protected hexaoctacontapeptide was treated with sodium in liquid ammonia. The ensuing sulfhydryl form was converted to the S-sulfonate form, which was reduced and then air-oxidized. The oxidized material was purified by gel filtration on Sephadex G-50 (fine) followed by ion-exchange chromatography on DEAE-cellulose. The cross-reactivity in the insulin radioimmunoassay of the ensuing product was 62.5 per cent of porcine proinsulin on a weight basis at B/Bo = 60 per cent. Acid hydrolysis and amino acid analysis of this product gave the theoretically expected ratios. In addition, this peptide, as well as the S-sulfonate form of the hexaoctacontapeptide, showed displacement curves superimposable on that of synthetic human C-peptide on an equimolar basis in the human C-peptide radioimmunoassay (antiserum 527). These results confirm the synthesis of human proinsulin.

A novel tRNA species as an origin of short interspersed repetitive elements (SINEs). Equine SINEs may have originated from tRNA(Ser).

Short interspersed repetitive elements (SINEs) were isolated from the equine genome and characterized. The equine SINE (ERE-1) family has several features characteristic of tRNA-derived retroposons. The five members of the equine family of SINEs are approximately 230 nucleotides in length and terminate with a sequence rich in oligo(A). They are all flanked by direct repeats at the 5' and 3' ends, and such repeats are the hallmarks of retroposons. In addition, the ERE-1 family has a tRNA-related region, which is similar to tRNA(Ser) of Drosophila (65% identity). tRNA(Ser) is a novel tRNA with respect to the origin of SINEs and has not previously been recognized among the twenty tRNA-derived SINEs characterized to date. The members of the ERE-1 family were found to be distributed among five species in the genus Equus, and their amplification may have contributed to the genetic variability of their hosts during evolution.

Synthesis of phenolic group containing analogues of porcine secretin and their immunological properties.

Syntheses by the conventional method are described of Nalpha-tyrosylsecretin, [Tyr1]secretin, and Nalpha-beta-(4-hydroxyphenyl)propionylsecretin. Secretin and [Tyr6]secretin were also prepared by the synthetic route identical with those employed for construction of the above analogues. Purification of secretin and the analogues was conducted by ion-exchange column chromatography on CM-Sephadex and gel filtration. Immunological reactivities of these analogues were examined in the radioimmunoassay system for secretin using two different antisera raised against synthetic secretin in rabbits. The tracers used in this study were [125I]-[Tyr1]secretin and [125I]-[Tyr6]secretin. The dose-response curves of Nalpha-tyrosylsecretin, [Tyr1]secretin, and Nalpha-beta-(4-hydroxphenyl)propionylsecretion were essentially superimposable upon those of natural and synthetic preparations of porcine secretin in the systems used, while [Tyr6]secretin showed discrepancy in the curve. In addition, biological activities of the synthetic polypeptides were compared with that of natural porcine secretin in term of exocrine pancreatic secretory response in anesthetized dogs.

Benzoquinoid ansamycins (herbimycin A and geldanamycin) interfere with the maturation of growth factor receptor tyrosine kinases.

Benzoquinoid ansamycins, such as herbimycin A (HA) and geldanamycin (GA), are antibiotics that exhibit anti-tumor effects. These compounds have been shown to result in the intracellular depletion of important growth signaling molecules. Recently, GA has been shown to bind tightly to Hsp90, thereby implicating Hsp90 as a possible chaperone for those signaling molecules adversely affected by the benzoquinoid ansamycins. Here we have investigated the effects of HA and GA on the synthesis, maturation and stability of different protein tyrosine kinases. Exposing cells to either compound blocked normal maturation of the epidermal growth factor (EGF) receptor, platelet-derived growth factor (PDGF) receptor, and pp60(v-src). We show that only the nascent forms of the EGF and PDGF receptors are degraded under these conditions. Once the newly synthesized receptors had been translocated into the endoplasmic reticulum membrane, addition of the drugs no longer affected their stability. For the cytoplasmic tyrosine kinase, pp60(v-src), both the nascent as well as the mature forms of the protein were degraded in cells treated with the drugs. We discuss these observations as they pertain to the possible role of Hsp90 as a substrate-specific molecular chaperone, perhaps involved in the maturation and/or stability of proteins important for growth control.

The hierarchical organization of decision making in the primate prefrontal cortex.

The prefrontal cortex plays an important role in making the association between sensory information and specific behavior. For example, in a complex stimulus response situation, such as the Wisconsin card sorting test, prefrontal patients show difficulty in making appropriate decisions. To understand the neural mechanisms, we recorded prefrontal cell activity while monkeys performed a go/no-go selective attention task where the subjects made a go or no-go response depending on the color or the motion direction of compound visual stimuli (moving colored dots). Groups of cells showed differential activity for go and no-go stimuli (go/no-go activity): some showed the activity either in the color or motion attending condition, and others showed the activity both in the color and motion conditions. Cells of shorter latencies, found mainly in the prefrontal subareas receiving visual input, showed go/no-go activity only when task demands necessitated that the monkeys attended to that cell's preferred visual dimension. We also found cells with longer latencies in the motor-related periarcuate area that showed go/no-go activity regardless of the dimension attended. These results suggest that subareas in the prefrontal cortex play different roles in associating the sensory information with its behavioral meaning and are hierarchically organized to make appropriate decisions in complex tasks.

Change in gene expression in facial nerve nuclei and the effect of superoxide dismutase in a rat model of ischemic facial paralysis.

Peripheral nerve injury induces changes in gene expressions of a variety of neuroactive substances in cell somata, which may have roles in the adaptive response to the injury, neuronal survival, growth and regeneration. In this study, we designed a rat model of ischemic peripheral facial paralysis with a selective embolization technique, and observed mRNA expression of calcitonin gene-related peptide (CGRP), c-jun, and growth associated protein (GAP)-43 in facial nerve nuclei using in situ hybridization histochemistry. The rats were demonstrated to have a transient facial paralysis consistently, and thus this method was regarded as a model of minor peripheral nerve injury. The mRNA of CGRP, c-jun and GAP-43 showed a distinct pattern of induction and time course of increase after the ischemic nerve injury. The results suggest that the small injury to the peripheral nerve was able to induce changes in mRNA expression in the cell body of motoneurons. We also investigated the protective effect of superoxide dismutase (SOD), which is a free radical-scavenging enzyme involved in cellular antioxidant defenses. The SOD treatment clearly alleviated the behavioral impairment and decreased the CGRP mRNA expression at 3rd day after injury. These data suggest that a free radical generated by the ischemia may be partially responsible for ischemic nerve damage and the change in gene expression in motoneurons.

Nerve growth factor applied onto the olfactory epithelium alleviates degenerative changes of the olfactory receptor neurons following axotomy.

The olfactory neuroepithelium of the mammalian nervous system manifests continuous neurogenesis throughout life. Recent studies suggest that neurotrophic factors and their receptors may play a role in the regulation of development and regeneration in the olfactory system. However, there have been very few in vivo studies investigating the effect of exogenous neurotrophic factors in the olfactory system. In the present study, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were administered into the rat olfactory mucosa for 5 days just after the transection of the olfactory nerve. We then examined the effect of exogenous neurotrophic factors on the degenerative changes in axotomized olfactory receptor neurons (ORNs). Further, we examined the location of their receptors, Trk A and Trk B. We found that both mature and immature ORNs expressed more intense signals for olfactory marker protein and beta-tubulin mRNAs, respectively, when NGF was applied to the axotomized olfactory neuroepithelium for 5 days, compared to the ORNs of saline-treated controls. BDNF at a 10 microg total dose did not show this effect. The effect of NGF applied onto the olfactory epithelium is consistent with the immunohistochemical finding that Trk A was present in the dendrites and axon bundles in normal and axotomized ORNs. These results suggest that NGF may protect the degenerative changes in mature and immature ORNs following axotomy through the binding to the Trk A receptor located on the surface of the olfactory epithelium.

Enhanced pulmonary absorption following aerosol administration of mucoadhesive powder microspheres.

Mucoadhesive, hydroxypropylcellulose (HPC) microspheres were prepared for powder inhalation and their feasibility for enhancing pulmonary drug absorption was investigated. Respirable-sized microspheres, incorporating crystalline or amorphous fluorescein (used as a model drug), were prepared by spray-drying aqueous or ethanol HPC systems, respectively. These were prepared from a variety of HPC grades (SL, L, M and H types) in different fluorescein-HPC ratios (1:1-1:10). The microspheres were administered to tracheally-intubated guinea pigs as powder aerosols and their fluorescein pharmacokinetics studied, and compared to those for pure crystalline fluorescein ('control'). All microspheres were prepared and aerosolized within a MMAD range of 1.3-2.6 microm (GSD< or =2.1). Fluorescein's dissolution was increased in the amorphous form by 6.5-fold when compared to the crystalline material (83.9-87.2 vs. 13.5 microg/ml, respectively). Poor dissolution for the 'control' crystalline fluorescein appeared to be rate-determined, which showed bi-phasic absorption profiles (T(max)=60 min), simultaneously competing with mucociliary clearance out of the lower airways. While the crystalline/HPC microspheres prolonged absorption, the amorphous fluorescein/HPC microspheres showed rapid absorption with T(max)=0 min (immediately after the administration had terminated). This was explained by enhanced fluorescein dissolution and was consistently observed irrespective of the fluorescein-HPC ratio or HPC grade. However, the microspheres with the least viscous HPC-SL and the lowest fluorescein-HPC ratio (1:1) failed to enhance bioavailability, presumably because the mucociliary clearance was undisturbed. In contrast, the microspheres with the highly viscous HPC-H with ratios > or = 1:4 successfully enhanced absorption, achieving 88.0% bioavailability by virtue of HPC increasing the dissolution and retarding the mucociliary clearance.

Interference from irrelevant features on visual discrimination by macaques (Macaca fuscata): a behavioral analogue of the human Stroop effect.

To study the operation of selective attention in a conflict situation with automatic processes, we trained 4 Japanese macaques (Macaca fuscata) extensively on a manual go/no-go task. The monkey had to discriminate either the color, shape, motion direction, or location of a visual stimulus. In each trial, the behavioral meaning of the relevant feature (go or no-go) could either be congruent or incongruent with irrelevant features of the same stimulus. Reaction times were slowed, and error rates increased when irrelevant stimulus features were incongruent with the required response. The effects were obtained when the monkey attended to the color, shape, or motion direction, but not when it attended to the location of the stimulus. The effects were cumulative so that the interference from 1 incongruent feature was smaller than that from 2 incongruent features. We propose that the present paradigm provides a behavioral analogue of the human Stroop effect.