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Biomedical subjects

E Yumoto

Publications and source records attributed to E Yumoto.

At least 19 recordsLinked to original sources

The effects of histamine and its antagonists on the cochlear microphonic and the compound action potential of the guinea pig.

OBJECT: we studied the effects of histamine, the H1 receptor antagonist pyrilamine, and the H2 receptor antagonist cimetidine on the cochlear potential of guinea pigs (cochlear microphonic, CM; compound action potential, CAP). METHODS: histamine was applied into the cochlear perilymph at three different dosages (10 microM, 50 microM or 10 mM). Pyrilamine and cimetidine were applied at 50 microM each. RESULTS: histamine increased the CAP at 10 and 50 microM without any significant effects on the CM. The effects of histamine at 50 microM were suppressed by the 50-microM of pyrilamine and cimetidine. At 10 mM of histamine, CAP and CM amplitudes were significantly decreased. CONCLUSION: in low concentrations, histamine may act as an extracellular signal on inner hair cells (IHCs) or it may stimulate the afferent nerve by binding to their H1 and H2 receptors. A possible explanation for the inhibitory effects of histamine at 10-mM dosage was apparently found in that the effects of the high concentration may be supraphysiological; and furthermore, there is a difference in the mechanism by which histamine exerts its effects mediated by the histamine receptors on the cochlea.

Administration, Topical↗

Clinical significance of p53 functional loss in squamous cell carcinoma of the oropharynx.

We examined the frequency of p53 mutations in 38 oropharyngeal squamous cell carcinomas (SCC), using both a yeast functional assay and a conventional immunohistochemical staining method (IHC) to detect p53 mutations. We also explored the clinical importance of p53 mutations in oropharyngeal SCC. An accumulation of p53 protein was detected in 17 of the 38 (45%) tumors by IHC, whereas the yeast-based assay detected 6 additional p53 mutations, for a total of 23 tumors (61%) with p53 mutations. The cDNA sequencing analysis revealed that the 6 mutations undetected by IHC consisted of 3 frameshift, 1 nonsense and 2 missense mutations. Thus, the yeast functional assay was more sensitive than conventional IHC for detecting p53 mutations. Subsequently, the relationship between p53 mutations and the clinico-pathological parameters in oropharyngeal SCC was evaluated using the results of the functional assay. Mutation of p53 was not associated with the patient age, sex, tumor stage or degree of tumor cell differentiation. Interestingly, heavy drinking had a significant positive correlation with the p53 mutation, but heavy smoking did not, suggesting that prolonged exposure to alcohol is more related to p53 mutation in oropharyngeal SCC than to tobacco consumption. Radiation sensitivity was examined by comparing tumor size on magnetic resonance images before and after completion of therapy with 45 Gy radiation, in the 18 cases of T2 oropharyngeal SCC that were initially treated by radiotherapy. The results showed that tumors with wild-type p53 decreased in size significantly compared to those with mutant p53. In 33 patients treated with curative intent, the overall survival after the completion of therapy was better in patients with a wild-type p53 tumor than in patients with a mutant p53 tumor. We conclude that p53 mutation is associated with radiation resistance and a decreased probability of survival in oropharyngeal SCC.

Adult↗

Serum interferon-gamma-inducing factor/IL-18 levels in primary biliary cirrhosis.

Primary biliary cirrhosis is an autoimmune disease of the liver in which T helper 1 cytokines predominate over those of T helper 2 in the pathogenesis. Interleukin- 18 (IL-18), for which the gene was recently cloned, is a novel T helper 1 cytokine, which augments interferon-gamma production. We designed this study to clarify the role of IL-18 in primary biliary cirrhosis and to examine whether serum IL-18 level can be a prognostic indicator for the disease. Serum IL-18 levels were measured using an enzyme linked immuno sorbent assay with mouse monoclonal antibodies. Twenty-two healthy volunteers, 31 patients with primary biliary cirrhosis (Scheuer's stage I, 13; II, 10; and IV, 8), 20 patients with autoimmune hepatitis, 11 patients with virus-related liver cirrhosis and six patients with obstructive jaundice were enrolled. Significant differences of serum IL-18 levels were observed between patients with Scheuer's stage IV and those with stage I, or II, virus-related liver cirrhosis and obstructive jaundice (P < 0.05). The IL-18 levels in primary biliary cirrhosis increased according to the disease progression, and fell promptly after living-related liver transplantation. Moreover, serum IL-18 levels in primary biliary cirrhosis were correlated with serum bilirubin concentrations and the Risk scores of the Mayo Clinic prognostic model for the disease. The IL-18 levels observed in patients with autoimmune hepatitis were also elevated, and correlated with the activity of the disease. These results indicate that serum interleukin-18 levels reflect the severity of primary biliary cirrhosis, the activity of autoimmune hepatitis, and may be an additive prognostic indicator in primary biliary cirrhosis.

Autoimmune Diseases↗

Analysis of individual specific cytotoxic T lymphocytes for two MAGE-3-derived epitopes presented by HLA-A24.

BACKGROUND: The human MAGE-3 gene encodes tumor-specific antigens that are recognized by cytotoxic T lymphocytes (CTLs) and expressed in a high percentage of various malignant tumors. Of the five MAGE-3-derived CTL epitopes identified to date, two nonapeptides (TFPDLESEF and IMPKAGLLI, designated MAGE-3.A24a and MAGE-3.A24b, respectively) can be expressed on the tumor surface by binding to the HLA-A24 molecule, which is the most frequent HLA class I molecule in Asian populations. To compare the immunogenecities of the two peptides, individual specific CTL lines were generated for each peptide (MAGE-3.A24a and MAGE-3.A24b). METHODS: Peripheral blood mononuclear cells (PBMCs) from four HLA-A24+ healthy donors were stimulated in vitro with autologous dendritic cells pulsed with MAGE-3.A24a, MAGE-3.A24b or both and were subsequently cultivated with a cytokine combination including interleukin-2. RESULTS: We succeeded in generating peptide-specific CTL lines in two of the four donors. The two CTL lines showed similar cytolytic levels against three MAGE-3+/HLA-A24+ cancer cell lines and also target cells pulsed with the corresponding peptide. Cytolytic activities were blocked by either anti-CD8 or anti-HLA-A24 monoclonal antibodies. CONCLUSIONS: The results suggest that MAGE-3.A24a and MAGE-3.A24b peptides have equal potential in inducing MAGE-3-specific and HLA-A24-restricted CTLs.

Antigens, Neoplasm↗

Two-dimensional analysis of vocal fold vibration in unilaterally atrophied larynges.

OBJECTIVE: Considerable inconsistencies regarding the vibratory pattern of the vocal fold among patients with unilateral vocal fold paralysis (UVFP) have been reported. These differences are derived from differences in the position, stiffness, and atrophy of the paralyzed vocal fold and other factors among patients. The purpose of this study was to assess the effects of unilateral atrophy of the vocal fold on vocal fold vibration. METHODS: Seven excised canine larynges were studied. The unilateral recurrent laryngeal nerve was severed to cause vocal fold atrophy in four of the seven. The lateral and vertical displacements were monitored simultaneously with photoglottography and a laser Doppler vibrometer, respectively. Videostroboscopy of each larynx was also performed before and after the experiment to translate photoglottographic output into absolute lengths. Atrophy of the unilateral vocal fold was confirmed histologically. RESULTS: The lateral amplitude was significantly greater than the vertical amplitude in all larynges. The Lissajous trajectories in the normal larynges were shaped like a reverse crescent. Vibration in the unilaterally atrophied larynges was periodical and symmetrical in phase when the thyroid ala on the atrophied side was pressed medially. The lateral and vertical amplitudes on the atrophied side were significantly greater than those on the normal side. The Lissajous trajectories differed from those of the normal larynges. CONCLUSIONS: In the absence of a prephonatory glottal gap, periodical vibration occurs in unilaterally atrophied larynges and the amplitude of vibrations of the atrophied vocal fold is greater in the lateral and vertical directions than that of the normal fold. This implies that phonosurgical procedures aiming at closure of the prephonatory glottal gap may have a beneficial effect on hoarseness in UVFP patients, although displacements of the vocal folds during vibration are not symmetrical.

Animals↗

Expression of fibroblast growth factor-2 in the nucleus ambiguus following recurrent laryngeal nerve injury in the rat.

OBJECTIVES: To examine fibroblast growth factor-2 (FGF-2) immunoreactivity in the nucleus ambiguus (NA) after three different recurrent laryngeal nerve (RLN) injuries. STUDY DESIGN: Immunohistochemical analysis of FGF-2. METHODS: Thirty adult rats underwent left-sided RLN crush (group A). The left RLN was transected in groups B (n = 30) and C (n = 30); in group C, both nerve stumps were covered with silicone caps. FGF-2 in the NA was assessed as the ratio of the positive areas on the left (operated [O]) and right (unoperated [U]) sides. The ratio (O/U) was measured 1, 3, 7, 14, and 28 days after the procedure. Three rats underwent left-sided RLN exposure and were killed 7 days later (control). RESULTS: Left-sided RLN paralysis occurred until day 28 in group A. In the control group, O/U was approximately 1. In group A, O/U was significantly elevated on day 7; in group B, on days 3, 7, and 14; and in group C, on day 3. O/U in group B was significantly greater than that in group A on days 14 and 28. Maximal FGF-2 immunoreactivity was significantly lower in group C than in groups A and B. CONCLUSIONS: We demonstrated elevated production of FGF-2 in the NA after RLN injury. This endogenous FGF-2 might contribute to preventing lesion-induced neuronal death. Blockage of axonal regeneration might suppress FGF-2 production in the NA. Further understanding of the roles of FGF-2 after RLN injury may contribute to the prevention of neuronal death and facilitation of axonal regeneration.

Animals↗

Assessment of stapes mobility by use of a newly developed piezoelectric ceramic device. A preliminary experiment in dogs.

A piezoelectric device was developed for assessment of stapes mobility during middle ear surgery. The device comprises a pair of ceramic bimorph elements: one for activation of the stapes and the other to pick up the vibration as an electric output, which varies in accordance with the stapes mobility, ie, the inverse of the cochlear input impedance (Zsc). The device is compact and easily manipulated even in the narrow surgical field of the ear. However, the measuring range is restricted to between 1 and 10 kHz. Measurement of Zsc was conducted with this device in 5 ears of 5 dogs. The mean magnitude of Zsc increased with frequency in the range from 1 to 10 kHz: 0.95 megohm at 1 kHz and 8.8 megohms at 10 kHz. After fixation of the stapes with dental cement, the magnitude increased to more than 10 megohms, except at 1 kHz. The results suggest that the device is useful in detecting decreases in stapes mobility in patients with chronic otitis media.

Animals↗

Initial steroid hormone dose in the treatment of idiopathic sudden deafness.

OBJECTIVE: The purpose of this study was to clarify whether higher doses of steroids improve the prognosis of idiopathic sensorineural hearing loss (ISHL) and the suitable dose of steroid hormone. STUDY DESIGN: The study was a retrospective statistical analysis. SETTING: This study was performed at the Department of Otolaryngology, Head Neck Surgery, Kumamoto University School of Medicine. PATIENTS: Two hundred fifty patients with ISHL were analyzed in this study. They were divided into two groups: those receiving less than a specified daily dose of steroid and those receiving a daily dose greater than or equal to the specified dose. INTERVENTIONS: The patients received systemic steroid therapy combined with adenosine triphosphate, vitamins, diuretics, vasodilators, hyperbaric oxygen therapy, stellate ganglion block, or volume expander. MAIN OUTCOME MEASURES: The correlation between the initial dose of steroid hormone and the improvement rate was analyzed. RESULT: Spearman's correlation coefficients and partial correlation coefficients between the initial dose and the prognosis were all significantly negative. On the other hand, the correlations between the initial dose and the prognosis were positive in the group receiving <30 mg/day, whereas they were negative in the group receiving > or =30 mg/day, although these correlations were not significant. CONCLUSION: The general use of steroid hormone to treat ISHL is not recommended. Furthermore, if steroid hormone is used for treatment, the use of <30 mg/day of prednisolone is preferable.

Adenosine Triphosphate↗

[Vascular anastomoses in free jejunal reconstruction to the neck vessels: an experience of consecutive 20 cases without using surgical microscope].

Twenty consecutive cases of pharyngoesophageal cancer who underwent free jejunal reconstruction were reported. The common carotid or external carotid artery was used for a feeder of the free graft. The internal jugular vein were served as a drainage vein. All anastomoses were performed in an end-to-side fashion without using surgical microscopes. Mean carotid artery clamping time was 16 minutes and no neurological complications were noticed postoperatively. Graft failure was occurred in 1 patient. The presenting technique, showing 95% success rate, is recommended as a simple option for vascular anastomosis in free jejunal reconstructive surgery.

Anastomosis, Surgical↗

Three-dimensional endoscopic images of vocal fold paralysis by computed tomography.

OBJECTIVE: To describe characteristics of 3-dimensional (3-D) computed tomographic (CT) endoscopic images of the larynx in unilateral vocal fold paralysis and the changes of the paralyzed vocal fold after phonosurgery as indicated by 3-D CT endoscopy. SETTING: A university medical center. PATIENTS: Twelve consecutive patients with unilateral vocal fold paralysis who underwent helical CT examination. Five of them underwent the CT examination before and after phonosurgical treatment. INTERVENTIONS: Three patients underwent arytenoid adduction, and 2 underwent type 1 thyroplasty. MAIN OUTCOME MEASURES: "Sagging," defined as caudal displacement of the vocal fold; and "thinning," defined as a decrease in the vertical thickness of the vocal fold and expansion of the ventricle on the affected side, were evaluated. RESULTS: Excessive motion artifacts in one patient prevented detailed description of his 3-D images. Sagging and thinning of the vocal fold and expansion of the ventricle on the affected side were noted on 6, 11, and 8 occasions, respectively. Adduction or augmentation of the paralyzed vocal fold after phonosurgery was observed in 3-D CT endoscopic images when displayed with bony densities. CONCLUSIONS: The use of 3-D CT endoscopy enables description of 3-D characteristics of unilateral vocal fold paralysis and supplements stroboscopic findings. Furthermore, CT endoscopic images, when simultaneously displayed with bony densities, may help in evaluating the effects of phonosurgical treatment of the paralyzed vocal fold.

Adult↗

Effects of PAF on histamine H1 receptor mRNA expression in rat trigeminal ganglia.

The application of platelet-activating factor (PAF) to the nasal mucosa of humans has been shown to increase histamine-induced hyper-reactivity. To test the hypothesis that PAF acts by increasing the reactivity of sensory nerve endings in the nasal mucosa to histamine, we examined PAF-stimulated rat trigeminal nerve ganglion cells. We found that relatively low concentrations of PAF (10(-12)-10(-9) M) induced increased histamine H1 receptor mRNA expression. This increase appeared as early as 1 h after PAF stimulation, peaked at 4 h, and disappeared after 24 h. The PAF receptor antagonist WEB2086 inhibited the increased expression of histamine H1 receptor mRNA induced by PAF, suggesting that the effects of PAF are mediated by specific receptors. This PAF effect was abolished by actinomycin D, suggesting that PAF induces de novo transcription of histamine H1 and/or PAF receptor mRNA. PAF may be important in the hyper-responsiveness of nasal mucosa exposed to histamine.

Animals↗

Genetic diagnosis of micrometastasis based on SCC antigen mRNA in cervical lymph nodes of head and neck cancer.

This study is designed to assess gene expression of squamous cell carcinoma antigen (SCCA) mRNA to detect micrometastases in cervical lymph nodes (LNs) of head and neck cancer. We examined the expression of SCCA mRNA in 12 primary tumors and 212 cervical LNs (101 LNs taken from 8 patients with tongue cancer, 71 from 7 patients with gingival cancer, 19 from 2 patients with laryngeal cancer, 9 from 2 patients with pharyngeal cancer, 7 from 1 patient with cancer of the buccal mucosa, and 5 from 1 patient with cancer of floor of the mouth). Detectability of metastatic LNs by nested and single reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with semiserial sections (hematoxylin-eosin staining and keratin immunostaining). All primary tumors expressed SCCA mRNA. Of 198 histologically metastasis-negative nodes, SCCA mRNA was detected in 37 (18.7%) by nested PCR. Eleven micrometastatic foci in 9 LNs (4.6%) were discovered by semiserial sectioning. This suggests that SCCA mRNA is a promising tumor marker for detecting the micrometastases in cervical LNs of head and neck cancer.

Antigens, Neoplasm↗

Postnatal changes in the types of muscle fibre in the canine inferior pharyngeal constrictor.

Deglutition is considered to be immature in infants and to mature postnatally. We evaluated postnatal changes in muscle fibre type composition in the canine inferior pharyngeal constrictor muscle, which consists of the thyropharyngeal (TP) and cricopharyngeal (CP) muscles, using ATPase staining with respect to the maturation of deglutition. In the TP muscle type IIA and type IIB fibres, the main components in the adult, were already predominant at 1 week postnatally. The percentage of primitive type IIC fibre showed a rapid reduction and reached the adult level within 6 weeks. In the CP muscle, the majority of fibres were type IIC at 2 weeks. At 2 months, more than 20% of the fibres were still type IIC and the proportion of type I fibres as a main component in the adult was smaller than that of the adult. None of the puppies younger than 9 weeks old had a fibre type composition similar to that of the adult. In the extensor digitorum longus and flexor digitorum superficialis, the compositions of muscle fibre types became similar to that of the adult at 6 and 9 weeks of age, respectively. Thus, the TP muscle matured more rapidly than the limb muscles, while the CP muscle matured more slowly. We speculated that the TP and CP muscles have specific individual differentiation patterns associated with their functional roles before and after birth, compared with the limb muscles.

Aging↗

Pliability of the vocal fold mucosa in relation to the mucosal upheaval during phonation.

OBJECTIVES: To quantitatively evaluate the effect of vocal fold lengthening on pliability of the mucosa measured along the superior-inferior axis and to examine the relation of the location of mucosal upheaval (MU) during phonation to the changes in pliability pattern of the mucosa when the vocal fold was lengthened. DESIGN: Investigation of mechanical characteristics of the vocal fold in relation to the MU during phonation. MATERIALS: Five excised canine larynges. INTERVENTIONS: Vibrations with and without vocal fold lengthening were recorded from the tracheal side via high-speed photography or video recording combined with stroboscopic illumination. Tattooed marks on the lower surface of the vocal fold were used to locate the MU. Pliability was defined as the maximal distance elevated in response to a constant focal negative pressure. RESULTS: Pliability decreased significantly (P=.05) when the vocal fold was lengthened. The point of minimal pliability and MU without vocal fold lengthening were located slightly above the area where the muscular layer approached the epithelial layer. They were located closer to the free edge of the vocal fold when it was lengthened than when it was not. Discrepancy of their locations when the vocal fold was lengthened was suggested. CONCLUSIONS: The MU occurs around the point of minimal pliability when the vocal fold is not lengthened, whereas the MU occurs slightly more laterally than the point of minimal pliability when the vocal fold is lengthened. Although further study is necessary to explain this discrepancy, the presence of the sparse deep layer of the lamina propria seems to be essential in the generation of the mucosal wave.

Animals↗

Histochemical study of the canine inferior pharyngeal constrictor muscle: implications for its function.

The inferior pharyngeal constrictor muscle (IPC), which consists of the thyropharyngeal (TP) and cricopharyngeal (CP) muscles. plays an important role during deglutition. The histochemical properties of the canine IPC muscle were investigated. The motor endplates of the TP muscle clustered at the midlength of the muscle, while those of the CP muscle were scattered diffusely. The glycogen depletion technique suggested that most of the CP muscle fibers terminated into the belly of the muscle and fiber lengths varied. With ATPase stain, type II fibers were shown to be predominant in the TP muscle, while type I fibers were predominant in the CP muscle. The diameter of the TP muscle fibers was significantly larger than that of the CP muscle. Although the histochemical characteristics of these two muscles were markedly different, they gradually changed, resulting in their coordinated physiological movements.

Adenosine Triphosphatases↗

Motor innervation of the guinea pig interarytenoid muscle: reinnervation process following unilateral denervation.

The authors investigated the process of denervation and reinnervation of the interarytenoid (IA) muscle in the guinea pig using transmission electron microscopy and glycogen depletion technique after unilateral transection of the recurrent laryngeal nerve (RLN) and superior laryngeal nerve to clarify the innervation pattern of the unpaired IA muscle. Anastomosis between the bilateral arytenoid branches was confirmed in the belly of the IA muscle. Five weeks after transection, all of the IA muscle fibers appeared to have been reinnervated by the contralateral RLN. As the arytenoid branch of the RLN runs together with that of the contralateral RLN in a single intramuscular nerve funiculus, it is possible that collateral sprouting branches grow and extend into the adjacent denervated Schwann's sheaths. The authors conclude that the unpaired IA muscle, as a whole, receives specific motor nerve supply from the bilateral RLNs, although each muscle fiber is innervated unilaterally.

Animals↗