Minoru Toriyama

Erythromycin inhibition of lipopolysaccharide-stimulated tumor necrosis factor alpha production by human monocytes in vitro

The mechanism of clinical effectiveness of low-dose and long-term erythromycin (EM) treatment for diffuse panbronchiolitis, sinobronchial syndrome, and associated otitis media with effusion was investigated by studying the effects of EM on tumor necrosis factor alpha (TNF-α) production by cultured human monocytes stimulated with lipopolysaccharide. At concentrations of 0.1 μg/mL or more, EM inhibited TNF-α release from human monocytes stimulated by lipopolysaccharide in a dose-dependent manner. Of the other macrolides tested, roxithromycin, an EM derivative, also showed significant inhibition of TNF-α production, whereas josamycin failed to inhibit TNF-α release from monocytes. Nonmacrolidic drugs such as minocycline hydrochloride, ofloxacin, or penicillin G had no significant effect on TNF-α production. These results suggest that the clinical improvement of chronic respiratory diseases by EM may depend on the suppression of production of inflammatory cytokines such as TNF-α.

Effect of single-drug treatment on idiopathic sudden sensorineural hearing loss

OBJECTIVES In order to evaluate the effect of a medical administration for the sudden deafness patients, single-drug treatment for idiopathic sudden sensorineural hearing loss (ISSHL) was assessed at multi-centers participating in the Acute Severe Hearing Loss Study Group sponsored by the Ministry of Health, Labor and Welfare of Japan. METHODS The subjects consisted of ISSHL patients who were (1) 20 years of age or older, (2) diagnosed within 2 weeks after the onset of hearing loss, (3) showing a mean hearing level of 40-90 dB at five frequencies from 250 to 4000 Hz, (4) previously untreated, and (5) with normal for age in hearing of the opposite ear. The drugs used in this study were ATP, alprostadil, hydrocortisone and amidotrizoate, which were administered intravenously, and beraprost sodium and betamethasone, which were given orally. Two drugs were assigned to each center, one of which was selected according to the code hidden in envelopes and administered for 1 week. The treatment after the single-drug administration was conducted at the discretion of each center. The hearing gain and recovery rate at 1 week after the initiation of single-drug treatment and at 1 month or over when the hearing level was fixed, were evaluated based on the criteria for hearing recovery prepared by the Acute Severe Hearing Loss Study Group. RESULTS There was no statistically significant difference in the recovery rate among drugs either at 1 week after the initiation of single-drug treatment or at the time of fixed hearing level. At the time when the hearing level was fixed, a statistically significant difference in the complete recovery rate was detected only between amidotrizoate and beraprost sodium. CONCLUSION From these results, we could not find any specific drugs recommended for ISSNHL. In evaluating the effect of the drugs, however, several problems in the clinical trial for ISSHL should be considered.

Cholesteatoma Debris as an Activator of Human Monocytes: Potentiation of the Production of Tumor Necrosis Factor

Tumor necrosis factor (TNF) is a cytokine which stimulates osteoclastic bone resorption and inhibits collagen synthesis in vitro. In this study the effect of human cholesteatoma debris and its constituents on the production of TNF-alpha by human monocytes in vitro was studied. Cultured human peripheral monocytes secreted TNF into the culture medium when exposed to cholesteatoma debris in a dose-dependent manner. The TNF production, however, was partially inhibited by the treatment of the debris with polymyxin B which inhibits biological activities of lipopolysaccharide (LPS). When individual constituents of cholesteatoma debris, i.e. keratin, cholesterol, lauric acid and LPS, were added to the cultured monocytes at concentrations equivalent to those in the debris, significant production of TNF was observed only with the keratin and LPS. These data suggest that cholesteatoma debris is a potent activator of the TNF production of human monocytes in vitro, and that LPS and keratin are responsible for the production.

Chronic Tonsillitis and IgA Nephropathy: Clinical Study of Patients with and without Tonsillectomy

To determine whether tonsillectomy is a significantly effective treatment in the clinical course of IgA nephropathy, we did a comparative study on 50 patients with IgA nephropathy and chronic tonsillitis. We divided the patients into two groups: 35 patients with and 15 without tonsillectomy (control group). With or without tonsillectomy, renal function became progressively worse during the follow-up period in most patients with a serum creatinine level of > 1.4 mg/dl at the time of renal biopsy. In patients with a serum creatinine level of < or = 1.4 mg/dl, renal function remained normal in all subjects with tonsillectomy, but worsened in 3 patients out of 13 without tonsillectomy. Improvement in proteinuria/hematuria was found more frequently in the tonsillectomized group than in the controls. Furthermore, the serum IgA level was significantly reduced after tonsillectomy, especially in patients showing improvement. From these results we conclude that tonsillectomy was effective for patients with IgA nephropathy complicated by tonsillitis when the operation was performed before deterioration of renal function.

Acute bilateral deafness with nephritis: A human temporal bone study†

Temporal bone pathology is described in a 37‐year‐old man who had acute, bilateral, profound sensorineural hearing loss without improvement 4 months before death. The patient had suffered from low complement nephritis, for which he had received prednisolone therapy. Autopsy revealed malignant lymphoma with non‐Hodgkins type, membranous proliferative glomerulonephritis and necrotizing vasculitis of middle and small arteries. In the temporal bone study, pathological changes were limited to the cochlear region. The vestibular structure showed no detectable pathological changes. The changes included total absence of the organ of Corti, atrophy and/or disappearance of the stria vascularis in the upper turns, collapse of Reissners membrane in the middle turn, and new bone formation in the apical turn.

Experimental Mumps Labyrinthitis in Monkeys (Macaca irus) —Immunohistochemical and Ultrastructural Studies

Three monkeys (Macaca irus) were inoculated with mumps virus into unilateral cochleas and their inner ear were examined by immunofluorescent microscopy and transmission electronmicroscopy. The temporal bones were removed after survival period of 14 days when serological tests disclosed elevation of anti-mumps antibody titers. Immunofluorescent microscopy revealed that the viral antigen was positive in the stria vascularis. The ultrastructural study revealed that the pathologic changes in the cochleas were marked in the organ of Corti and stria vascularis. The outer hair cells were more susceptible to the infection than the inner hair cells. In the stria vascularis, both marginal and intermediate cells were affected. It was possible to find some of marginal cells in the basal turn shedding a large number of mature virions into the endolymph. These pathologic changes observed in the cochleas of the monkeys were similar to those previously revealed in the guinea pig cochleas and thus were considered as the specific features of acute mumps labyrinthitis.

Activation of Peritoneal Macrophages with Human Cholesteatoma Debris and α-Keratin

The effect of human cholesteatoma debris on mouse peritoneal macrophages was studied in vivo. The number of macrophages and lymphocytes increased 5 days after injection of the debris into the peritoneal cavity. A similar increase in peritoneal cells was observed when an urea-extracted fraction of the cholesteatoma debris or α-keratin, a major component of the debris, was injected. Both cholesteatoma debris- and α-keratin-elicited macrophages exhibited a greater response of luminol-dependent chemiluminescence upon exposure to zymosan, suggesting that the elicited macrophages were activated. In contrast, other constituents of the debris, such as cholesterol or fatty acid—with the exception of lipopolysaccharide (LPS)—failed to elicit or activate peritoneal macrophages at the similar doses detected in the debris. The chemiluminescent response of macrophages obtained by injecting LPS was, however, much lower than that of a-keratin-induced macrophages. These results indicate that cholesteatoma debris is capabl...

Virus-like particles in human vestibular ganglion cells

SummaryWe found intracytoplasmic aggregates of virus-like particles in human vestibular ganglion cells. These particles were always observed in the peripheral area of the cytoplasm. Morphological characteristics of the cytoplasm are similar to those of other ganglion cells. The inclusion bodies are round and measure about 1.7 μm in maximum diameter. They consist of a porous convoluted dense material and virus-like particles. The overall diameter of 118 randomly selected particles varies from 36 nm to 73 nm, and the mean value is 53 nm. Most of the particles are spherical while a few possess a hexagonal or semicircular profile. The particles exhibit a double external membrane or vesiculated external layer. Most of the particles are empty. There are, however, some particles which show vesicular structures in their content. Although our present data are insufficient to determine these particles as viral, their hexagonal shape and size are similar to true virus. With these data in mind, we suggest that these particles might be a dormant form of virus and may possibly produce infectious disease in the inner ear.

Morphological changes of vestibular ganglion cells in human fetuses and in pediatric patients

The temporal bone histopathology of human vestibular ganglion cells of fetuses and pediatric patients was studied. In the first study, we traced the morphological changes in vestibular ganglion cells in human fetuses ranging from 13 weeks to 39 weeks of gestational age by using 13 temporal bone serial sections. Vestibular ganglion cells had reached histological maturity by the 24th week of gestation and the volume of vestibular ganglion cell cytoplasm increased until the 39th week of gestation. In the second study, the temporal bone serial sections of seven neonates, eight infants and five children were investigated to reveal pathological changes in vestibular ganglion cells. Morphological changes in vestibular ganglion cells in human fetuses were revealed. Vestibular ganglion cells were changed pathologically by intracranial disease and variety etiology affecting the inner ear, because these are located in the internal auditory canal between the brain and labyrinth.

Wirkung von Stickstoffdioxid auf das Riechepithel

An 8 Wochen alien Wistar-Ratten (n = 35) wurde der Effekt von Stickstoffdioxid (NO2) – einer Hauptkomponente der Luftverschmutzung – auf das Riechepithel untersucht. Die Tiere wurden uber 14 Tage 10 ppm NO2 ausgesetzt (Nationalinstitut fur Umweltstudien, Tsukuba, Japan). Das Riechvermogen der Tiere wurde anschliessend mittels Verhaltensolfaktometrie getestet. Nach der Totung wurden die Riechschleimhaute morphologisch und immunhistochemisch auf das mikrotubulusassoziierte Protein 5 (MAP 5) untersucht. MAP5 wird normalerweise in den neurinalen Zellkorpern und entlang ihrer Neuriten nachgewiesen und als Fruhzeichen eines aktiven axonalen Wachstums gedeutet. Histomorphologisch wurden Veranderungen der olfaktorischen Zilien und eine Erhohung der Anzahl der Bowman-Drusen unmittelbar nach der NO2-Exposition beobachtet. Alle Veranderungen im Riechepithel bildeten sich innerhalb von 14 Tagen nach der Exposition zuruck, jedoch hatten die exponierten Ratten Riechstorungen bis zum 30. Tag. In den Kontrolltieren konnte MAP5 diffus in den Neuriten der Riechzellen nachgewiesen werden, wahrend sich bei den exponierten Ratten MAP5 in signifikant starkerer Konzentration bis zu 30 Tage nach der Exposition fand. Der Nachweis der Aktivitat von MAP5 korrelierte mit der durch Verhaltensolfaktometrie festgestellten Geruchsstorung. Die morphologischen Veranderungen, die sich schnell zuruckbildeten, besassen nur geringe Aussagekraft hinsichtlich der Riechfahigkeit.