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Biomedical subjects

S Takeno

Publications and source records attributed to S Takeno.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effect of cysteamine on gastric nerve fibers containing gastrin-releasing peptide in the rat.

In rats, changes in gastric nerve fibers containing gastrin-releasing peptide (GRP) in cysteamine-induced duodenal ulcer were investigated in relation to the dynamics of gastrin-producing cells (G-cells). Marked increases in gastric acid secretion and serum gastrin level were observed from 2 h after the administration of cysteamine. The number of G-cells was significantly decreased from 2 h after the injection of cysteamine. Two and 4 h after the administration of cysteamine, the G-cells showed ultrastructural changes characterized by a markedly decreased number of secretory granules. Circulating GRP levels were significantly elevated from 2 h after the administration of cysteamine. In the control group given vehicle only, nerve fibers showing immunoreaction for GRP formed a fine network in the gastric wall and were densely distributed in the oxyntic mucosa, located close to capillaries and demonstrated varicosities that contained either small clear vesicles or GRP-immunopositive vesicles with large cores. Eight h after the administration of cysteamine, there was depleted GRP immunoreactivity, evidenced by a markedly decreased number of vesicles, with large electron-dense cores, in the oxyntic mucosa. These findings suggest that, in cysteamine-induced duodenal ulcer, alterations in gastric nerve fibers containing GRP may be related to hypergastrinemia.

Animals↗
PubMed1996

Otoacoustic emission amplification after inner hair cell damage.

Otoacoustic emissions (OAEs) are considered to originate from active cochlear processes involving the outer hair cells (OHC). These emissions are suppressed by activity in the efferent olivocochlear bundle (OCB) and following OHC damage caused by noise exposure or ototoxic drugs. Temporary enhancement of OAEs may occur following noise exposure, and permanent enhancement of emissions has been associated with primary afferent dysfunction in the auditory system. This suggests that there are active adaptation processes in the cochlea exist that could potentially compensate for loss of afferent input. We have used the anti-cancer drug carboplatin to induce selective inner hair cell (IHC) lesions in the cochleae of chinchilla and measured the elevation of auditory thresholds that occurred using brainstem responses (ABR). Following carboplatin treatment click evoked otoacoustic emissions (CEOAEs) were amplified from cochlear frequency regions, which demonstrated extensive IHC damage but apparently normal OHCs. These results support the theory that OHCs cells are involved in the production of these cochlear emissions but also provides further evidence that active adaptation processes exist in the cochlea. It is postulated that loss of afferent input reduces the activity in the medial efferent OCB resulting in de-suppression of OHC contractility. Enhanced OHC contractility could then produce amplification of CEOAEs.

Acoustic Stimulation↗
PubMed1996

Recording from the inferior colliculus following cochlear inner hair cell damage.

The anti-cancer drug carboplatin has been used to generate inner hair cell (IHC) lesions in the cochleae of chinchilla. This model has provided a valuable physiological tool for the study of the auditory system, particularly concerning the relative roles of IHCs and outer hair cells (OHCs). We recorded responses to contralateral sound stimuli of single units (SU) in the central nucleus (CN) of the inferior colliculus (IC) from normal and carboplatin treated animals. Normal single unit thresholds and frequency tuning curves (FTCs) were found, despite gross IHC damage within the cochleae of carboplatin treated animals. No evoked afferent responses could be detected in CN regions which represented cochlear loci where total IHC loss had occurred. Normal frequency selectivity in the auditory system is possible with small numbers of surviving IHCs provided OHCs remain normal.

Animals↗
PubMed1996

[Proliferating cell nuclear antigen (PCNA) immunolocalization in human nasal epithelium with chronic sinusitis detected by confocal laser scanning microscopy].

This study examines the immunohistological localization of proliferating cell nuclear antigen in the nasal and paranasal sinus epithelium from a group of patients undergoing sinus surgery for chronic sinusitis. PCNA immunoreactivity as determined by fluorescence intensity and the density of labeled cells as assessed by confocal laser scanning microscopy. The control group consisted of seven specimens taken from patients with post operative maxillary cyst and optic nerve canal fracture. In this group, most of the labeled cells were located on the basal cell layers with a few on the intermediate cell layers. The average labeled cell densities were 57.3 cells/mm2 on the basal cell layers and 15.9 cells/mm2 on the intermediate cell layer. The sinusitis group consisted of eleven patients. In contrast with the control group, the sinusitis epithelium displayed a significantly high proportion of goblet and intermediate cells positively stained for PCNA. The average densities were 84.9 cells/mm2 on the basal cell layers and 133.1 cells/mm2 on the intermediate cell layers in this group, the latter being nearly ten fold greater than that in the control group. Epithelial PCNA expression was correlated with the degree of inflammatory cell infiltration assessed by serial sections for each sample. A positive correlation was observed between these two factors (R = 0.63, Pearson). We believe that epithelial cell turnover is accelerated in chronic rhinosinusitis due to continuous exposure to various pathogens and host immune interventions. In those cases, goblet and intermediate cells would play the major role in enhanced epithelial proliferation.

Chronic Disease↗
PubMed1996

The neonatal chinchilla cochlea: morphological and functional study.

The developmental time scale of the cochlea varies from species to species. We investigate here the condition of the neonatal cochlea in the chinchilla, a species increasingly used in auditory research. We have examined the morphology of cochlear hair cells using scanning microscopy, and the development of auditory function during the first postnatal month by monitoring auditory brainstem evoked responses (ABR). We find that although there were some outer hair cell kinocilia present in middle and apical areas, the hair cells otherwise were mature at 24 hours after birth. Furthermore, cochlear auditory thresholds are adult-like at birth. However, whilst there was little change in ABR thresholds over one month, there is evidence of continued maturation of the central auditory system as shown by the shortening of the PI-P5 latency from 9.1 ms to 7.7 ms.

Animals↗
PubMed1995

Carboplatin ototoxicity in the chinchilla: lesions of the vestibular sensory epithelium.

Carboplatin (cis-Diammine-1,1-cyclobutane dicarboxylate platinum II; CBDCA) is a second generation platinum analog with less nephrotoxicity and cochlear ototoxicity than cisplatin, the first generation platinum chemotherapeutic agent. Studies in many animal species have indicated that carboplatin ototoxicity is expressed as damage to cochlear outer hair cells. The lesion is similar, though less severe, than that resulting from cisplatin intoxication. Recent investigations by our laboratory have demonstrated a species-specific ototoxicity of carboplatin in the chinchilla cochlea. Contrary to other animal models, the inner hair cells are the focus of damage; the outer hair cells often sustain little or no damage. Clinical evidence points to vestibular dysfunction in some patients treated with platinum-containing anti-tumoural agents. However, no morphological studies have shown degeneration of the sensory cells in the vestibular labyrinth resulting from carboplatin treatment. The objective of the present study was to determine whether, in view of its unique toxicity in the chinchilla, carboplatin has any toxic effect on the vestibular end organs. Preliminary investigations of the vestibule by light and scanning electron microscopy indicate that sensory cell cilia became exfoliated or deformed in the crista, utricle and in one instance in the saccule. In general the pattern of damage is similar to that caused by other known ototoxic agents including aminoglycosides and cisplatin.

Animals↗
PubMed1994

Cochlear function after selective inner hair cell degeneration induced by carboplatin.

The ototoxicity of carboplatin, a second generation anti-cancer agent, was examined using the chinchilla as an animal model. In animals treated with a clinical therapeutic dose (400 mg/m2), the dominant degenerative change is to inner hair cells (IHCs). This is in sharp contrast to most other ototoxic agents, which damage primarily the outer hair cells (OHCs). Functional changes to the cochlea have been evaluated in carboplatin treated subjects by recording cochlear action potentials (CAP) and cochlear microphonics (CM); cochlear lesions were evaluated using scanning electron microscopy. In carboplatin treated animals, CAP thresholds to tone-pip stimuli were elevated in proportion to IHC damage in corresponding cochlear regions. In contrast, CM amplitudes and 'thresholds' remained close to normal in most cases, reflecting the preservation of OHCs in the basal turn. These results indicate a high degree of independence between the inner and outer hair cell systems in the cochlear transduction mechanism. We suggest that this species-specific preparation with selective IHC loss will provide a valuable tool for studying, separately, the role of OHCs in both afferent and efferent cochlear function.

Acoustic Stimulation↗
PubMed1994

The uncinate process: a histological and morphological study.

The uncinate process (UP) has become a familiar anatomical landmark to otolaryngologists due to the increasing popularity of functional endoscopic sinus surgery (FESS) in recent years. This study examines the histological and morphological features of UPs removed from a group of patients undergoing FESS operations for chronic sinusitis. The structure of the UP by light microscopy (LM) is reported. A relatively high proportion of goblet cells and seromucous glands was noted. Scanning electron microscopy (SEM) identified four surface cell types on the UP. Furthermore, four categories of surface morphology were noted. The most common appearance was of predominantly ciliated cells. A nonciliated surface ultrastructure is associated with a longer history of sinonasal symptoms and a higher incidence of surgical intervention.

Adult↗
PubMed1994

Selective inner hair cell ototoxicity induced by carboplatin.

Carboplatin is a second-generation platinum antineoplastic agent. It has biological activity similar to cisplatin and is currently recommended for the treatment of ovarian cancer. In clinical use, carboplatin appears less ototoxic than cisplatin. This paper reports the ototoxic effects of carboplatin, in doses equivalent to the clinical use of the drug, in the chinchilla. Intravenous carboplatin 200 to 400 mg/m2 by bolus injection caused significant ototoxicity in this model as revealed by brainstem evoked responses (ABR audiometry). The cochlear pathology as seen by scanning electron microscopy revealed predominantly inner hair cell (IHC) stereocilia damage. Furthermore, the extent (grade) of the morphological lesions appears to be well correlated with the auditory brainstem response pattern of threshold elevation.

Animals↗
PubMed1994

The early development of sino-nasal mucosa.

The development of human nasal mucosa was studied in 20 fetal heads between 8 and 24 weeks of gestation. Initially the nasal cavity is lined by a single layer of flattened cells, which produces two to three layers of undifferentiated spherical cells. Olfactory epithelium lines the cranial portion of the human fetal nasal cavity at 8 weeks of gestation. Pseudostratified ciliated cuboidal or columnar epithelium appears at 9 weeks of gestation in the nasal cavity and between 14 and 16 weeks of gestation in the primitive ethmoid sinuses and maxillary sinus infundibulum. Goblet cells and glandular acini appear between 12 and 14 weeks of gestation. Initially these goblet cells/glands are found predominantly in the anterior nasal cavity but are more evenly distributed at 24 weeks of gestation. The epithelial development of the nasal septum generally precedes that of the lateral nasal wall. This study documents nasal mucosal maturation and associated anatomic development in the human fetus.

Embryonic and Fetal Development↗
PubMed1994

Induction of selective inner hair cell damage by carboplatin.

Carboplatin (diammine [1,1 cyclobutane dicarboxylato (2)-0,0'] platinum) is an anti-cancer agent which can be toxic to the inner ear. We have explored the nature of this ototoxicity in the chinchilla. In this species, initial degenerative changes appear to be restricted to the inner hair cell (IHC) regions of the organ of Corti. This finding is intriguing and unusual since all other known ototoxic drugs, such as aminoglycosides, are predominantly associated with outer hair cell damage. In the present study, the mechanism of ototoxicity was investigated by comparing two different routes of carboplatin administration. Carboplatin was administered either intravenously (i.v.) or intraperitoneally (i.p.). The mode of administration influenced electrophysiological and morphological changes. Hearing thresholds were elevated in the i.v. group significantly more than in the i.p. group at all tested frequencies. The degree of hair cell damage was evaluated by scanning electron microscopy at four frequency regions in each cochlea. IHC damage in the i.v. group was significantly more severe than in the i.p. group. Carboplatin effects on a different species, the guinea pig, were also determined to clarify interspecies differences. In the guinea pig, outer hair cell damage occurred sporadically and inner hair cells remained intact. In contrast, chinchilla inner hair cells are susceptible to the ototoxic effects of carboplatin. The degree of hair cell damage appears to be dependent on the peak level of carboplatin rather than on the total dose. This animal model provides a new tool for the investigation of inner and outer hair cell function.

Animals↗
PubMed1993

Comparative developmental toxicity and metabolism of nitrazepam in rats and mice.

This study was designed to evaluate the developmental toxicity of nitrazepam (NZ) in Sprague-Dawley rats and ICR mice and to determine the metabolic factors which modulate susceptibility to the developmental effects of NZ. Rats were treated orally with a single dose of NZ at 300 mg/kg on Day 12 of gestation. Mice received one dose of 300 mg/kg NZ via gavage between Days 9 and 14 of gestation. NZ administration resulted in a significant incidence of malformations in rats, while no evidence of teratogenic action was observed in mice. Pronounced species differences in the metabolism of NZ were observed. In rats, 7-acetylaminonitrazepam (AANZ) was detected as the major metabolite in plasma and embryos, whereas in mice, only small amounts of this product were found. The rate of N-acetylation of 7-aminonitrazepam (ANZ) to AANZ was 8.5-fold greater in rat liver cytosol than that in mouse liver cytosol. In contrast, the rate of deacetylation of AANZ to ANZ was 9-fold greater in mouse liver microsomes than that in rat liver microsomes. The developmental effects of authentic metabolites of NZ were studied in the two species. A single oral administration of 300 mg/kg ANZ to pregnant animals produced a significant incidence of malformations in rats, but not in mice. On the other hand, AANZ was teratogenic in both species. These results suggest that the difference in the susceptibility to NZ-induced teratogenicity between rats and mice may be related to differences in the levels of N-acetyltransferase and deacetylase, and that AANZ may be involved in the teratogenic mechanism.

Abnormalities, Drug-Induced↗
PubMed1993

Carboplatin ototoxicity: an animal model.

A new animal model of ototoxicity is presented using intravenous carboplatin in adult chinchillas. A range of physiological and morphological effects was produced using doses calculated from the recommended therapeutic range (200-400 mg/m2). Auditory thresholds to tone pips stimuli were monitored using brain stem evoked responses (ABR). Cochlear histopathology was studied by light microscopy (LM) and ultrastructural hair cell abnormalities investigated with scanning electronmicroscopy (SEM). Carboplatin in this animal model predominantly affected the inner hair cells. This may provide an important model for the study of selective loss of the main afferent input in the auditory system.

Animals↗
PubMed1993

[Tissue culture of guinea pig middle ear epithelium--morphological characterization and proliferative activities of cultured cells on fibroblast-reorganized collagen gels].

Long-term culture of the middle ear epithelium of guinea pigs was carried out on reconstituted floating collagen matrix. Fibroblasts established from the abdominal skin dermis of allogenic animals were used to reorganize hydrated collagen gels into a dermal-like matrix. The explants placed on the surface of these matrices were composed of pseudostratified columnar cells with polygonal flat outgrowth sheets, which could be maintained for up to one month. In contrast, with simple hydrated collagen gel, no lysis of the substrate was observed regarding this reorganized collagen gel. In order to examine the growth pattern of these culture cells, 5-bromodeoxyuridine (BrdU) was added to the medium during the entire culture period. The specimens were immunohistologically stained using monoclonal antibodies. Noticeable changes were observed in the marginal portion of the explant where the cell shape changed from cuboidal to squamous. In this transitional area, most cells showed positive staining and consequently high proliferative activity. In the central area of the explants, however, the number of positive cells decreased and the main observation was a few labeled basal cell nuclei. It was suggested that the same regenerative process which usually occurs in normal respiratory epithelia after mechanical injury or other insults, was replayed in this culture system.

Animals↗
PubMed1993

Tissue culture of middle ear epithelium using fibroblast-reorganized collagen gels.

The middle ear epithelium of the guinea pig has been cultured on a modified floating collagen matrix. Fibroblasts harvested from abdominal skin dermis of allogenic animals were used to reorganize hydrated collagen gels into a dermal-like matrix. Within two days, the explants placed on the surface of these matrices showed proliferation of polygonal "outgrowth cells" which could be maintained for up to one month. During the first two weeks of the culture period, dividing cells were frequently identified. These cells were especially abundant in the marginal area of the explants and consisted of pseudostratified columnar cells. The reorganized collagen gel matrix was stable and did not dissolve even after the "outgrowth cells" became confluent. The present system should allow further elucidation of the growth and differentiation mechanisms of middle ear epithelial cells.

Animals↗