Nobuhisa Terada

Mechanism of eosinophil infiltration in the patient with subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (Kimura's disease). Mechanism of eosinophil chemotaxis mediated by candida antigen and IL-5.

Kimuras disease is a chronic granulomatous disease of unknown etiology. Although eosinophilia is one of the characteristic features in this disease, little is known about the mechanism of eosinophilia. In the present study it was demonstrated that interleukin-5 (IL-5) was produced and released from the site of a granuloma and lymph nodes after stimulation with candida antigen. It was also shown that peripheral blood eosinophils from patients with Kimuras disease contained a large proportion of hypodense eosinophils and that their viability was prolonged. These results strongly suggest that locally produced IL-5 induced by candida antigen contributes to the eosinophilia in this disease.

Mode of Action of a Topical Steroid on Immediate Phase Reaction After Antigen Challenge and Nonspecific Nasal Hyperreactivity in Nasal Allergy

This study compared the effects of 2-week administration of a topical steroid (fluticasone propionate [FP] 100 micrograms twice daily) with placebo in 28 patients with perennial nasal allergy who were allergic to house dust and mites in a double-blind randomized study. The number of inflammatory cells and decidual epithelial cells and concentrations of tryptase and eosinophil cationic protein in nasal lavages, and reactivity of the nasal mucosa to histamine and to antigen were investigated. The topical steroid, FP, significantly inhibited all of these assessments. The degree of improvement of nasal reactivity to histamine significantly correlated with the degree of decrease in eosinophil cationic protein levels.

Interleukin-5 Gene Expression in Nasal Mucosa and Changes in Amount of Interleukin-5 in Nasal Lavage Fluid After Antigen Challenge

Eosinophils and their products are known to cause hyperreactivity and swelling of the nasal mucosa in subjects with nasal allergy. Interleukin-5 (IL-5) not only induces differentiation and proliferation of immature eosinophils but also causes mature cells to accumulate and activate. This study shows that IL-5 is actually produced in the human nasal mucosa by antigen challenge, and it further investigates the changes in the amount of IL-5 in nasal lavage fluids after antigen challenge. Expression of mRNA for IL-5 in nasal mucosa was investigated using the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis. Among the 4 subjects with nasal allergy examined in this study, expression of mRNA for IL-5 was observed in 2 prior to antigen challenge; within 6 h after antigen challenge it was seen in 3 subjects. We also found that the amount of IL-5 in the nasal lavage fluids obtained consecutively after antigen challenge increased predominantly in the late phase, and that the number of eosinophils in the IL-5 positive group was significantly higher than that in the IL-5 negative group. These results strongly suggest that IL-5 contributes to the recruitment of eosinophils in the nasal mucosa of the subjects with nasal allergy.

Gait analysis in patients with vertigo.

SummaryGait analysis utilizing foot switches and electromyography of antigravity muscles was performed on 31 patients with vertigo. Twenty-one cases had peripheral vestibular lesions (such as vestibular neuronitis, Menieres disease, traumatic labyrinthitis, small acoustic neuroma), and 10 cases had central lesions (such as spinocerebellar degeneration, pontine glioma, cerebellar tumor and giant acoustic neuroma). Parameters employed for analysis included time from heel strike to forefoot strike (HA-I), time from heel off to forefoot off (HA-II) as well as durations of stance, swing and (initial) double supports (DS). Fourteen healthy adults served as controls. The overall incidence of abnormality was highest in HA-1, followed by stance and swing. The occurrence of abnormalities in stance, swing and DS was higher in the central lesion when compared with the group having peripheral lesions. The significance and usefulness of gait analysis for dizzy patients are discussed.

Effects of Female Hormones on the Muscarinic and α1-Adrenergic Receptors of the Nasal Mucosa

During pregnancy aggravation of nasal allergic symptoms is occasionally observed in subjects with nasal allergy. To evaluate the effect of female hormones on the muscarinic receptor and the alpha 1-adrenergic receptor of the nasal mucosa, receptor binding assay was performed using the nasal mucosa of pregnant guinea pigs and of male guinea pigs; the latter were treated either with estrogen or with progesterone. Pregnancy induced a significant decrease of the density of the alpha 1-adrenergic receptor of the nasal mucosa (p less than 0.05). Estrogen induced a significant increase of the density of the muscarinic receptor (p less than 0.05), while progesterone induced a significant decrease of the density of the alpha 1-adrenergic receptor of the nasal mucosa of guinea pigs. When similar changes of the receptor can be induced by female hormones in the nasal mucosa of the human subjects, this may facilitate secondary development of hyperreactive nasal symptoms in subjects who have been sensitized before without apparent nasal symptoms.

Analysis of Gait in Patients with Peripheral Vestibular Disorders

Analysis of gait in patients with acute unilateral peripheral vestibular disorders was performed using foot switches and electromyography, with the aid of a telemetry system. Among the eight parameters set for the analysis, the occurrence rate of abnormality in the coefficient of variation (CV) was the highest (78%) for the time from heel strike to forefoot strike, followed by that of the location of maximum monophasic contraction of the gastrocnemius during stance, swing and stance. No significant laterality concerning the abnormally increased CV value in those parameters was found except for swing of the foot contralateral to the lesion side. The CV value of each parameter was significantly increased by removing visual cues, suggesting the importance of visual input for steady locomotion. No significant change in CV values of double support was obtained during the acute stage of vestibular neuronitis, indicating that weight transfer from one leg to the other could be smooth even though some difficulty was expected. Abnormal parameters at an acute stage returned to normal limits at recovery stage. The physiological background of the obtained results is discussed.

Changes of Adrenergic and Muscarinic Cholinergic Receptors in Nasal Mucosa in Nasal Allergy

Receptor-binding assays were performed to evaluate the changes of beta- and alpha 1-adrenergic and muscarinic receptors in the nasal mucosa of subjects with nasal allergy and in guinea pigs sensitized with ovalbumin using radioligands 3H-DHA, 3H-prazosin and 3H-QNB, respectively. In subjects with nasal allergy, a decrease in density of beta- and alpha 1-adrenergic receptors and an increase in density of muscarinic cholinergic receptors were observed. An increase in density of muscarinic cholinergic receptors could be reproduced in the nasal mucosa of guinea pigs which were sensitized with ovalbumin and had typical hyperreactive nasal symptoms. These results indicate that the increase in the density of muscarinic receptors observed in the nasal mucosa of subjects with nasal allergy has been induced secondarily by an allergic reaction in the nasal mucosa with hyperreactive nasal symptoms, which in turn acts as an aggravating factor in the vicious circle promoting hyperreactivity of the nasal mucosa.

Interleukin-5 upregulates intercellular adhesion molecule-1 gene expression in the nasal mucosa in nasal allergy but not in nonallergic rhinitis

The effect of interleukin-5 (IL-5) on intercellular adhesion molecule-1 (ICAM-1) gene expression in human nasal mucosa was studied using the method of gene expression quantification. Recombinant human IL-5 was shown to induce ICAM-1 gene expression in the nasal mucosa of patients with nasal allergy, but not in the mucosa of non-allergic patients. The peak level of ICAM-1 gene expression was seen 6 h after IL-5 stimulation. In the nasal mucosa of patients with nasal allergy, IL-5 might act not only as an eosinophil chemotactic factor, but also as an enhancement factor for the expression of adhesion molecules, thereby accelerating eosinophil appearance. The results also suggest that the nasal mucosa of patients with nasal allergy somehow favors adhesion molecule induction by IL-5.

Cholinergic Muscarinic Receptor in the Nasal Mucosa of Guinea Pigs with Bronchial Asthma with and without Hypersensitive Nasal Symptoms

Using [3H]-quinuclidinyl benzilate (QNB) as a radioligand, receptor binding assay was performed to evaluate the changes of the muscarinic receptor in the nasal mucosa of guinea pigs sensitized with toluene diisocyanate (TDI), which showed hypersensitive airway symptoms both in the lower airway and in the nose. The same study was performed in guinea pigs sensitized with bacterial crystalline alpha-amylase (BCA) which showed typical symptoms of bronchial asthma but without hypersensitive nasal symptoms. In the nasal mucosa of guinea pigs sensitized with TDI, an increased density of the muscarinic receptor was confirmed with no change in affinity of the receptor. However, in the nasal mucosa of guinea pigs sensitized with BCA, no changes were observed either in the density of the muscarinic receptor of the nasal mucosa or in its affinity. The increased density of the muscarinic receptor observed in subjects with nasal allergy, which was reported earlier, is not specifically related to IgE-mediated nasal allergy and is not induced by systemic sensitization itself but is assumed to be induced by some pathophysiological changes in the nasal mucosa including antigen-antibody reaction with development of hypersensitive nasal symptoms.

Responses of Resistance and Capacitance Vessels in Human Nasal Mucosa to β-Receptor Agonists

To investigate the responses of nasal vessels, divided into resistance and capacitance vessels, to a beta-receptor agonist in human, mucosal blood flow of the inferior turbinate and nasal airway resistance were measured when 1.5 mg terbutaline was applied topically. Mucosal blood flow was measured by the hydrogen clearance method just beneath the site where terbutaline in physiological saline (0.02 ml) was applied on an extremely localized area of the nasal mucosa. Nasal airway resistance of the ipsilateral and contralateral nasal cavities was measured separately by anterior rhinomanometry when terbutaline in normal saline (0.1 ml) was sprayed in the unilateral nasal cavity. Topical application of terbutaline elicited neither a significant increase of mucosal blood flow of the inferior turbinate nor an increase of nasal airway resistance. beta-Receptors seem not to be as densely distributed both in the resistance vessels and in the capacitance vessels as to cause vasodilatation by their activation in the nasal mucosa.