Naonobu Takeuchi

Diesel exhaust particles stimulate human airway epithelial cells to produce cytokines relevant to airway inflammation in vitro

BACKGROUND Epidemiologic and experimental studies suggest that air pollution such as diesel exhaust particles (DEPs), one of the important air pollutants, may play a role in the increasing prevalence of allergic airway diseases. OBJECTIVE We studied the effect of suspended particulate matter (SPM) and its main component, DEPs, on the production of IL-8 and granulocyte-macrophage colony-stimulating factor (GM-CSF) by human airway epithelial cells in vitro. METHODS SPM obtained from high-volume air samplers and DEPs were added to cultured human nasal polyp-derived upper airway, normal bronchial, and transformed bronchial epithelial cells. Production of GM-CSF and IL-8 by airway epithelial cells was evaluated. RESULTS Nontoxic doses of DEPs showed a significant stimulatory effect on IL-8 and GM-CSF production by these three kinds of epithelial cells in a dose- and time-dependent fashion. SPM had a stimulatory effect on GM-CSF, but not IL-8, production. These effects were abrogated by treatment with a protein synthesis inhibitor, cycloheximide, suggesting that the process required a de novo protein synthesis. On the double-chamber plates, airway epithelial cells responded to DEPs only when they were stimulated from the apical sides, which can be a model for in vivo environments. Neither charcoal nor graphite showed such stimulatory effects, indicating that the activity of DEPs did not derive from their particulate nature. Benzo(a)pyrene, one of the main aromatic hydrocarbons contained in DEPs, showed a stimulatory effect on the release of the cytokines, and this organic substance might have a causative effect on of the potency of DEPs. CONCLUSION We conclude that SPM and DEPs, its main component, might be important air pollutants in the activation of airway epithelial cells for the release of cytokines relevant to allergic airway inflammation.

Immunohistochemical Localization of Histamine Receptor Subtypes in Human Inferior Turbinates

Histamine is an important chemical mediator in allergic rhinitis and plays an important role in eliciting the nasal symptoms of the disorder. However, the immunohistochemical localization of histamine receptor subtypes (H1R, H2R, H3R, and H4R) in human nasal mucosa is unknown. There are also no prior studies of H3R and H4R in human nasal mucosa. The objective of this study was to examine the distribution of histamine receptor subtypes in the human inferior turbinates by an immunohistochemical method. H1R was localized primarily in the epithelium, vessels, and nerves. H2R was localized primarily in the epithelium and the glands. H3R and H4R were clearly distributed on the nerves. In addition, H1R, H3R, and H4R were clearly localized on the same nerves. This result indicates that H1R, H3R, and H4R adjoin and regulate each other in the same nerves. All histamine receptor subtypes may play some role in patients with allergic rhinitis.

Noninvasive system for evaluating allergen-induced nasal hypersensitivity in murine allergic rhinitis

Until now there has been no method for physiologically evaluating nasal hypersensitivity in mice. Enhanced pause (Penh) has been used as an indicator that reflects changes in the lower airway. Recently, however, there is disagreement regarding the significance of the Penh system; this is because Penh is not essentially a physiological parameter, and it might not necessarily represent a change in the lower respiratory tract. The purpose of the present study is to investigate whether Penh could be applicable for analyzing nasal hypersensitivity in mice. BALB/c mice were sensitized with ovalbumin (OVA) through a combination of intraperitoneal injection and daily intranasal challenge in an awake condition. Penh was measured at each time point during sensitization, or a serial change in Penh value was followed after the final nasal challenge and the effect of treatment was assessed. Following sensitization and nasal challenge, the Penh value gradually increased and showed a significant difference on day 14. Changes in IgE, eosinophil infiltration into nasal mucosa, and OVA-induced symptoms all strongly correlated with the increase in Penh. On day 19, after OVA nasal provocation, Penh gradually increased and reached maximal values 25 min after the challenge. Pretreatment with dexamethasone or a histamine H1 blocker significantly suppressed this increase in Penh. We confirmed that intranasal OVA challenge did not induce bronchoconstriction by measuring airway resistance and bronchoalveolar lavage fluid, and through histological examination. These results clearly demonstrate that Penh could be a useful noninvasive indicator for studying nasal hypersensitivity.

Prediction of the prognosis of Bell's palsy using multivariate analyses.

Objectives: This study aimed to establish more reliable formulae for predicting the prognosis for patients with Bells palsy at initial examination. Patients: One hundred four consecutive patients with Bells palsy whose facial movement was either completely recovered or unchanged for more than 6 months. Intervention: Diagnostic. Main Outcome Measures: Multivariate analyses were performed using the following variables: Age, House-Brackmann score (H-B), electroneuronography (ENoG), nerve excitability test (NET), blink reflex, and stapedial muscle reflex on initial examination. Results: Duration to maximal recovery can be predicted with the adjusted coefficient of 0.51 using H-B, ENoG, stapedial muscle reflex, and NET. Whether complete recovery would be achieved can be predicted with the Nagelkerke coefficient of determination of 0.72 using age, H-B, ENoG, and NET. Conclusion: This study suggested that the prognosis of patients who recovered early can be predicted more precisely; however, the prognosis of patients who recovered late and incomplete could not be predicted easily.

Age-related changes in cell density and the proliferation rate of olfactory ensheathing cells in the lamina propria of postnatal mouse olfactory mucosa

We investigated age-related changes in the distribution and proliferation of olfactory ensheathing cells (OECs) in postnatal mouse olfactory mucosa. In contrast to reported data on other glial cell types in the peripheral and central nervous systems, OEC cell density in the olfactory nerve bundles in the lamina propria remained almost constant from 10 days through 16 months of age. Electron microscopy of the nerve bundles revealed that axon packing density also was constant during that period. These findings suggest that the ratio of the number of OECs to the unit length of the olfactory neuron axons ensheathed by them does not change markedly throughout the lifetime of mice in an undisturbed condition. By contrast, OEC proliferative density decreased rapidly in the 10-day to 1-month-old period, showing a significant difference, and for the rest of life remained at low level, similar to previous values reported for other glial cell types.

Dexamethasone modifies the effect of Pseudomonas aeruginosa Exotoxin A on hearing

In the present study, the protective effect of dexamethasone was analysed following exposure of the cochlea to

Musashi-1 expression in postnatal mouse olfactory epithelium.

We investigated the age-related change in the distribution of a molecular marker for neural stem and precursor cells, Musashi-1, in the olfactory epithelium of mice from 1 day up to 16 months of age using immunohistochemistry. We also compared the distribution pattern of Musashi-1 with that of growth-associated protein 43, the olfactory marker protein, and Notch-1. Musashi-1 was expressed in the globose basal cell layer and the lower part of the growth-associated protein 43-positive layer, with immunoreactivity decreasing with aging. Notch-1 was observed only in the early postnatal period. These findings are consistent with the fact that globose basal cells are proliferating olfactory precursor cells and that their ability to generate new neurons decreases with aging.

Preoperative Embolization for Paraganglioma

We have applied a new method of preoperative embolization to an intravagal and to carotid body paraganglioma, using estrogen dissolved in absolute alcohol and polyvinyl alcohol particles, which diffusely embolizes vessels from capillaries to main feeders. Total resection of the tumors after embolization was successively performed without postoperative complications; total blood loss was 205 and 130 ml, respectively, and the surgical time was approximately 3 hours in both cases. The technique, characteristics, and advantages of this method are discussed.

Nasal allergic response mediated by histamine H3 receptors in murine allergic rhinitis

Background: Histamine is one of the most important chemical mediators causing nasal allergic symptoms, and H1 receptor antagonist have been used as the treatment first choice in nasal allergy. The presence of H3 receptors has also been determined in the human nasal mucosa, but few studies have investigated the involvement of H3 receptors in nasal allergy.

Ultrastructural arrangement of collagen fibrils in the rat facial nerve

We studied the collagen fibril arrangement in the connective tissue sheaths (epineurium, perineurium, and endoneurium) of the intratemporal and extra-temporal portion of the rat facial nerve by transmission electron microscopy after fixing the nerves with tannic acid, and by scanning electron microscopy after digesting cellular elements by sodium hydroxide treatment. These studies revealed that the epineurium consists of thick bundles of collagen fibrils and a coarse meshwork of collagen fibrils, the perineurium consists of a lacework sheet of bundles of collagen fibrils, and the endoneurium consists of a meshwork of fine collagen fibrils in the inner layer and of longitudinally oriented bundles of collagen fibrils in the outer layer. There was little difference in the three-dimensional organization of collagen fibrils between the extra-temporal segment and vertical and horizontal segments of the facial nerve. However, the facial nerve lost the epineurium and perineurium in the central portion of the horizontal segment near the geniculate ganglion and in the labyrinthine portion, i.e. the proximal portion of the intratemporal segment. In these segments, the endoneurium consisted of a meshwork of fine collagen fibrils.