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Biomedical subjects

G Mogi

Publications and source records attributed to G Mogi.

At least 73 records · Page 4Linked to original sources

Experimental otitis media with effusion induced by middle ear effusion.

Experimental otitis media with effusion was induced in chinchillas by middle ear effusion, which was induced by an injection of immune complex into the tympanic cavity. To elucidate the pathogenesis of otitis media with effusion, cytologic and biochemical findings of the effusion and histopathology of the middle ear mucosa of effusion-induced chinchillas were compared with those of experimental otitis media with effusion induced by different procedures; eustachian tube obstruction, intratympanic inoculation of endotoxin, and immune reaction. No significant differences were seen in cytology, biochemistry, and histopathology among OMEs induced by these procedures. However, middle ear effusions, when compared with the corresponding sera, were proven to contain higher amounts of histamine and prostaglandin E2. These findings seem to demonstrate that middle ear effusion containing a large number of inflammatory mediators is essential for induction and prolongation of inflammatory reaction in the middle ear.

Animals↗

[Seasonal fluctuations of substance P and vasoactive intestinal peptide concentrations in nasal secretions of patients with nasal allergy to Japanese cedar pollen].

Substance P (SP) and vasoactive intestinal peptide (VIP) concentrations in nasal secretions and plasma from patients with nasal allergy to Japanese cedar pollen and healthy volunteers were measured from Jan to Dec, 1991 using EIA established by us. Simultaneously, the numbers of airborne pollens of Japanese cedar and cypress were counted, and the relation to the SP and VIP concentrations in nasal secretions from the patients with nasal allergy to Japanese cedar pollen was studied. The mean SP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 81.9 +/- 48.4 fmol/mg protein, which was significantly higher than that in the non-pollination season (30.4 +/- 14.7 fmol/mg protein) (p < 0.01). Likewise, the mean VIP concentration in nasal secretions from the patients with nasal allergy to Japanese cedar pollen in the pollination season was 14.2 +/- 10.4 fmol/ml protein, which was significantly higher than that in the non-pollination season (4.2 +/- 3.0 fmol/mg protein) (p < 0.01). The SP and VIP concentrations in nasal secretions from the healthy volunteers were not affected by the scattering of pollens. The SP and VIP concentrations in plasma from the patients and the healthy volunteers were not affected by the scattering of pollens.

Adult↗

Lymphocyte-mucosal interaction of the middle ear mucosa.

The middle ear mucosa possesses immunologic features similar to those of the peripheral mucosa sites in the common mucosal immune system and after mucosal immunization, antigenspecific IgA-forming cells appear in the inflamed mucosa of the tympanic cavity. Recent investigations suggest that lymphocyte migration to lymphoid tissues is regulated by lymphocyte-high endothelial venules (HEV) interaction. However, the lymphocyte migration mechanism to the middle ear mucosa is still unclear. We investigated whether or not organ-specific determinants which lymphocytes bind with are present on the middle ear mucosa by in vivo and in vitro lymphocyte adherence assays by using fluorescein-labeled lymphocytes from various lymphoid tissues. Many lymphocytes from Peyer's patches and hilar lymphnodes adhered on the inflamed middle ear mucosa with or without mucosal immunization, while these cells were not found on the normal tympanic mucosa. The number of the cells was smaller than that in the gastrointestinal mucosa. Lymphocyte adherence to the middle ear mucosa was not suppressed by anti-T cell antibody. These findings suggest that the middle ear mucosa possesses organ-specific mucosal determinants which B-lymphocytes selectively bind with, and that those determinants which regulate lymphocyte migration to the middle ear mucosa differ from those of other mucosae in the gastrointestinal tract.

Animals↗

The role of type I allergy in secretory otitis media and mast cells in the middle ear mucosa.

To clarify the role of type I allergy in the etiology and pathogenesis of secretory otitis media (SOM), clinical and experimental studies were done. The distribution of mast cells in the tubotympanum of normal and developing guinea pigs was also investigated. Our clinical study revealed that the ratio of complications of nasal allergy (NA) in 222 SOM-young children is 42%, while that of SOM in 259 NA-young children is 35%. These ratios were significantly higher than those seen in control group which consists of 104-children randomly selected from a kindergarten and elementary school. Findings of our animal experiment showed that the eustachian tube is involved, both functionally and morphologically, in type I allergic reactions of the nose. The tubal dysfunction evoked by nasal allergic reactions was transient, not culminating in middle ear effusion (MEE). However, this dysfunction interferes with the clearance of MEE. Our studies suggest that type I allergic reactions of upper respiratory tracts are factors indicative of a chronic state of disease, rather than a cause of SOM. In adult guinea pigs, the density of mast cells was highest in the pharyngeal orifice of the eustachian tube. The density was higher in the adult than in developing guinea pigs. Mast cells in the middle ear mucosa appeared in areas covered by ciliated epithelia or areas richly vasculized. The results of our investigation suggest that mast cells distribute in the tubotympanum responding to continuous stimuli to the tubotympanic cavity.

Animals↗

Undecalcified temporal bone morphology: a methodology useful for gross to fine observation and three-dimensional reconstruction.

Using a novel method of cutting undecalcified temporal bone specimens, quantitative structural analysis in the human and the Japanese monkey was undertaken. One millimeter thick serial slices made from unembedded temporal bones retained fine structure. Therefore, gross to fine observation could be performed systematically at the macroscopic, light, scanning, and transmission electron microscopic levels. The entire temporal bone three-dimensional reconstruction was completed from embedded sections; consequently, the volume of the tubotympanum and air cell system could be calculated. Available methods by embedding, tungsten carbide sectioning, grinding, and microwave irradiation for decalcification were also examined. These morphologic studies suggest that these novel methods offer timesaving advantages over any presently available techniques, and allow for elucidation of temporal bone morphology with only a few specimens.

Animals↗

Oral vaccine therapy for pneumococcal otitis media in an animal model.

We investigated whether mucosal IgA response in the middle ear cavity against Streptococcus pneumoniae type 19F is enhanced by use of enteric capsules, and whether the resulting mucosal immunity can prevent pneumococcal otitis media. Adult Hartley guinea pigs were employed. With intratympanic inoculation of 10(5) and 10(6) live S pneumoniae, the occurrence of pneumococcal otitis media significantly decreased in guinea pigs that received intraduodenal and intragastric immunization by enteric capsules. In these guinea pigs, the values of salivary IgA antibody titers against S pneumoniae were significantly greater, and histologic changes of the middle ear mucosa were also slighter than those of control guinea pigs. These findings indicate that oral vaccination by enteric capsules elicits mucosal IgA responses, as well as intraduodenal immunization, to prevent pneumococcal otitis media. These results suggest the possibility of clinical application of oral vaccination by enteric capsules for the prevention of middle ear infection.

Administration, Oral↗

Role of phagocytes in antimicrobial defence of the middle ear.

The role of phagocytes in the antimicrobial defence of the middle ear was investigated in this experiment, using Hartley strain guinea pigs with an experimental otitis media. Otitis media was induced with an inoculation of Streptococcus pneumoniae into the tympanic cavity through the ear drum. For depletion of peripheral blood phagocyte population such as monocytes and polymorphonuclear neutrophils (PMNs), whole body irradiation (250 rad or 500 rad) was carried out on guinea pigs three days before S. pneumoniae inoculation into the middle ears. Carrageenan was also used for selective depletion of mononuclear cells, to distinguish their role from polymorphonuclear neutrophils. In control animals, otitis media was induced reproducibly with middle ear inoculation of more than 10(6) S. pneumoniae. In irradiated animals, which underwent 10(2) or 10(4) S. pneumoniae inoculation, the incidence of otitis media because of S. pneumoniae infection became higher in accordance with the dosage of irradiation. However, no significant difference was seen in the occurrence of otitis media and the number of viable bacteria recovered from bulla washings between controls and carrageenan-treated animals. These results suggest that phagocytes, particularly neutrophils, are essential for antimicrobial defense at the early phase of the middle ear infection with S. pneumoniae.

Animals↗

Congenital middle ear cholesteatoma: report of 3 cases.

In this report, we presented 3 cases of congenital middle ear cholesteatoma which occurred in a 12-year-old girl, a 4-year-old boy, and a 6-year-old boy. In all 3 cases, there was a whitish mass behind a normal tympanic membrane. Congenital middle ear cholesteatoma is not a rare disease. In the early stage, it is asymptomatic. But when it progresses, this disorder can destroy conductive systems of the middle ear and cause many symptoms. One patient (Case 1) had a complaint of hearing impairment. She underwent mastoidectomy and tympanoplasty; however, the cholesteatoma recurred. The other 2 patients had no symptoms. The abnormal appearance of their tympanic membrane was found by chance at their local otologists. We performed tympanotomies and removed cholesteatomas without aftereffects. When otologists note an abnormal appearance behind a normal tympanic membrane, with or without symptoms, tympanotomy should be done due to the possibility of congenital middle ear cholesteatoma.

Audiometry↗

Distribution of mast cells in the tubotympanum of guinea pigs.

The distribution pattern of mast cells in the middle ear mucosa and eustachian tube was examined histologically in adult and developing guinea pigs. The aim was to better understand the role of mast cells in the middle ear defense mechanism. The density of mast cells was highest in the pharyngeal orifice of the eustachian tube, and decreased in the direction of the tympanic orifice. The density was higher in adults than in developing animals. Mast cells were also found in the tubotympanic membrane of the fetal guinea pig. Mast cells in the middle ear mucosa appeared in areas covered by ciliated epithelia or areas richly vascularized. Almost all mast cells found in the middle ear and eustachian tube mucosa were the connective tissue type. The results of this investigation suggest that mast cells distribute in the tubotympanum in response to continuous stimuli to the tubotympanic cavity.

Animals↗

Inhibition of bacterial adherence by nasopharyngeal secretions.

The role of secretory immunoglobulin (Ig) A in nasopharyngeal secretions in the adherence of Streptococcus pneumoniae and Hemophilus influenzae to nasopharyngeal epithelial cells was investigated in vitro. The adherence was remarkably reduced by treating bacteria with nasopharyngeal secretions, and the antiadhesive activity was significantly greater in nasopharyngeal secretions having secretory IgA antibody activity against bacteria than in those having no activity. Noticeable changes were not observed in the antiadhesive activity caused by absorption of IgG from nasopharyngeal secretions. Results suggest that secretory IgA in nasopharyngeal secretions is related to bacterial adherence and adds to the prevention of nasopharyngeal infections.

Antibodies, Bacterial↗

Distribution of immunocompetent cells in normal nasal mucosa: comparisons among germ-free, specific pathogen-free, and conventional mice.

To better understand the role of immunocompetent cells in the defense mechanism of the upper respiratory tract against microbial invasions, the distribution patterns of those cells were investigated in nasal mucosa of mice maintained in three different conditions: germ-free (GF), specific pathogen-free (SPF), and conventional (CV) conditions. Immunostaining by the indirect peroxidase method and toluidine blue staining were employed for the detection of immunocompetent cells and mast cells. For immunostaining, anti-IgG, -IgA, and -IgM polyclonal antibodies and anti-Lyt-1, -Lyt-2, and -Mac-1 monoclonal antibodies were used as primary antibodies. In nasal mucosa of CV mice, Mac-1+ cells, mast cells, and all cell types of lymphocyte subsets were present. In nasal mucosa of SPF mice, all cell types were also positive, but fewer in number than those of CV mice. In nasal mucosa of GF mice, IgG+, IgA+, and Lyt-2+ cells were rare, although IgM+ and Lyt-1+ cells were present in small numbers. An electron microscopic study revealed that follicle-like lymphocyte aggregates with high endothelial venules were present in nasal mucosa close to the mucosal epithelia. These findings suggest that lymphocytes are mobilized to nasal mucosa, responding to continuous antigenic stimuli, and play an important role in the local defense mechanism of the upper respiratory tract.

Animals↗

Analysis of immunocompetent cells in the middle ear mucosa.

A quantitative analysis of immunocompetent cells in the middle ear mucosa of mice was carried out by an indirect immunostaining method using various monoclonal antibodies. Mice bred in germ-free, specific pathogen-free, and conventional conditions were used to examine nonimmunized middle ear mucosa. Middle ear mucosae of otitis media-induced mice were also examined. In normal middle ear mucosa, mast cells were substantial, followed by Mac-1-positive cells and lymphocytes. Even though IgA-, IgM-, and Lyt-1-positive cells were seen in the mucosa of conventional mice, IgM-positive cells were seen only in mucosae of specific pathogen-free and germ-free mice. In otitis media-induced mice by inoculation with nontypable Haemophilus influenzae or lipopolysaccharide, Mac-1-positive cells were dominant. Although the numbers of IgM- and Lyt-1-positive cells increased markedly, the numbers of other lymphocyte subsets did not increase until 14 days after inoculation. These findings suggest that the middle ear is immunologically a potential organ as long as it is not exposed to antigenic stimulation. It is considered to be an immunoreactive site only after it has been activated with pathogens.

Animals↗

Influence of nasal allergic reactions on the clearance of middle ear effusion.

In order to investigate the influence of nasal allergic reactions on the clearance of middle ear effusion, an animal model of nasal allergy and otitis media with effusion was produced in the same guinea pigs simultaneously by passive sensitization with serum of homologous animals containing IgE antibodies (for nasal allergy) and by inoculation of immunocomplex into the tympanic cavity (for otitis media with effusion). Usually, middle ear effusion appeared within 2 to 3 days and disappeared within 7 to 9 days after the inoculation of immunocomplex. Three days after the inoculation of immunocomplex, intranasal antigen challenge was performed three times daily and continued until the animals were killed. Disappearance of middle ear effusion appeared to be delayed in animals in which nasal allergic reactions were induced. Middle ear effusion was not found in those ears that were not inoculated with immunocomplex. Findings of the present study indicate that IgE-mediated allergic reactions of the mucous membrane lining the nose, nasopharynx, and eustachian tube constitute a factor indicative of a chronic state of disease, rather than a cause of otitis media with effusion.

Animals↗

Three-dimensional images of the temporal bone and experimental otitis media in Japanese monkeys.

Since the middle ear structure of animals commonly used for experimental study is different from that of humans, we used the Japanese monkey (Macaca fuscatus) as an animal model for otitis media with effusion (OME). The exact similarities and differences of the ear structure between humans and Japanese monkeys were studied by the use of computer-aided three-dimensional reconstruction, in addition to light and electron microscopy. Otitis media with effusion was repeatedly induced by direct intratympanic inoculation of one of the following: keyhole limpet hemocyanin; following systemic immunization with keyhole limpet hemocyanin, Streptococcus pneumoniae; or endotoxin. The temporal bones were serially sliced with a diamond band saw, after which the histologic findings were examined by light and electron microscopy on the basis of macroscopic observations. Each substance induced OME equally, 2 to 3 days after inoculation. Inflammatory reaction of the middle ear mucosa extended to all of the air cells; subsequently, the inflamed mucosa returned to normal in each case along with normalization of both the tympanometric and otoscopic findings. No remarkable architectural change remained, even after OME was induced repeatedly. These findings are applicable to acute otitis media and acute mastoiditis. The development of chronic middle ear effusion was not observed in this study. The usefulness of the diamond band saw and computer-aided analysis for temporal bone histologic evaluations is emphasized.

Acute Disease↗

The role of bacterial adherence in otitis media with effusion.

Adherence of nontypable Haemophilus influenzae and Streptococcus pneumoniae to nasopharyngeal epithelial cells was investigated in vitro. Both strains had higher affinity to the epithelial cells of children than to those of adults. In children, the adherence was significantly greater in patients with otitis media with effusion than in normal subjects. Secretory IgA in nasopharyngeal secretions was found to have antibody activity against the bacteria. Adherence of both bacteria was significantly smaller in the group having secretory IgA antibody activity than in the group having no activity. These results suggest that bacterial adherence to the nasopharynx may play an important role in the pathogenesis of otitis media with effusion in children, and that secretory IgA in nasopharyngeal secretions may be related to the decrease of adherence.

Adult↗

Type I allergic reactions of the middle ear and eustachian tube: an experimental study.

To clarify the role of type I allergic reactions in etiology and pathogenesis of otitis media with effusion and to determine whether or not the middle ear is an allergic "shock" organ, we made animal models of nasal allergy in guinea pigs by passive sensitization with serum of homologous animals containing specific IgE antibodies. We also examined the eustachian tube, tympanic cavity (histologically), and tubal function after the induction of type I allergic reactions of the nose. However, the involvement of histologic changes was limited only up to the area near the pharyngeal orifice. The tubal dysfunction evoked by nasal allergic reactions was transient, culminating in no middle ear effusion. Upon direct antigen-challenge into the tympanic cavity, allergic changes were observed in the mucosa lining the tympanic bulla, even though no microscopic effusion was present. Findings of the present study suggest that type I allergic reactions of the nose are not an etiologic factor for otitis media with effusion, although the middle ear is potentially an allergic shock organ.

Animals↗

Secretory IgA and bacterial adherence to nasal mucosal cells.

The ability of Streptococcus pyogenes to adhere to nasal mucosal cells was investigated by an in vitro assay system in order to clarify the actual role of secretory IgA in mucosal immunity in the nose. The number of bacteria adhering to isolated mucosal cells was significantly larger in patients with chronic sinusitis than in normal control subjects. The ability of bacteria to adhere, however, was significantly lower in the group of subjects having specific secretory IgA antibody activity to the M protein than in those having no secretory IgA activity. Findings demonstrated that mucosal immunity preventing or blocking the adherence of bacteria is impaired in patients with chronic sinusitis.

Antigens, Bacterial↗