Rie Nomiya

CRTH2 plays an essential role in the pathophysiology of Cry j 1-induced pollinosis in mice

PGD2 is the major prostanoid produced during the acute phase of allergic reactions. Two PGD2 receptors have been isolated, DP and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), but whether they participate in the pathophysiology of allergic diseases remains unclear. We investigated the role of CRTH2 in the initiation of allergic rhinitis in mice. First, we developed a novel murine model of pollinosis, a type of seasonal allergic rhinitis. Additionally, pathophysiological differences in the pollinosis were compared between wild-type and CRTH2 gene-deficient mice. An effect of treatment with ramatroban, a CRTH2/T-prostanoid receptor dual antagonist, was also determined. Repeated intranasal sensitization with Cry j 1, the major allergen of Cryptomeria japonica pollen, in the absence of adjuvants significantly exacerbated nasal hyperresponsive symptoms, Cry j 1-specific IgE and IgG1 production, nasal eosinophilia, and Cry j 1-induced in vitro production of IL-4 and IL-5 by submandibular lymph node cells. Additionally, CRTH2 mRNA in nasal mucosa was significantly elevated in Cry j 1-sensitized mice. Following repeated intranasal sensitization with Cry j 1, CRTH2 gene-deficient mice had significantly weaker Cry j 1-specific IgE/IgG1 production, nasal eosinophilia, and IL-4 production by submandibular lymph node cells than did wild-type mice. Similar results were found in mice treated with ramatroban. These results suggest that the PGD2-CRTH2 interaction is elevated following sensitization and plays a proinflammatory role in the pathophysiology of allergic rhinitis, especially pollinosis in mice.

Membranous labyrinth volumes in normal ears and Meniere disease: a three-dimensional reconstruction study.

The purpose of this study was to determine the normal volume ranges of cochlear duct, saccule, and utricle, and to assess endolymphatic hydrops in Ménière disease.

Generalized arteriosclerosis and changes of the cochlea in young adults.

Hypothesis: To disclose the histopathologic findings of the cochlea in young adults with generalized arteriosclerosis. Background: It is well known that arteriosclerosis begins and progresses during childhood. Although the relationship between arteriosclerosis and auditory function in elderly people was examined in many reports, the histopathologic effect of arteriosclerosis on the cochlea in young adults has not been studied. Methods: This study involved quantitative analysis, including the number of spiral ganglion cells, the loss of cochlear outer hair cells, and the areas of stria vascularis and spiral ligament. It included 10 temporal bones from 6 subjects with generalized arteriosclerosis and 10 age-matched normal control temporal bones from 7 subjects. Results: The mean number of spiral ganglion cells in the cochlea with generalized arteriosclerosis was significantly lower than that in normal controls in the basal turn. The mean loss of outer hair cells in the cochlea with generalized arteriosclerosis was significantly greater than that of normal controls in the basal and apical turns. The stria vascularis and spiral ligament were severely atrophic, with generalized arteriosclerosis in the basal turn. There was no significant difference in the thickness of the spiral modiolar artery between generalized arteriosclerosis and normal controls. Conclusion: Degeneration of the cochlea, especially in the basal turn, was already apparent in young adults with generalized arteriosclerosis.

Vascular findings in the stria vascularis of patients with unilateral or bilateral Ménière's disease: a histopathologic temporal bone study.

Hypothesis: There are pathologic changes of vessels in the stria vascularis in patients with Ménières disease. Background: The cause of Ménières disease is under debate. Methods: This study examined 14 temporal bones from 7 patients with bilateral Ménières disease, 30 temporal bones from 15 patients with unilateral Ménières disease, and 17 age-matched, normal temporal bones from 12 subjects. The temporal bones were serially sectioned in the horizontal plane at a thickness of 20 &mgr;m and stained with hematoxylin and eosin. The midmodiolar section of the cochlea was selected from each subject, and the number of vessels in the stria vascularis in each cochlear turn was counted by light microscopy. The area of the lumen of each vessel in the stria vascularis was also measured. Results: The number of vessels in the stria vascularis in ears with Ménières disease was smaller than in normal controls in all cochlear turns. The number of vessels in the contralateral stria vascularis in patients with unilateral Ménières disease was smaller than in normal controls in all cochlear turns. There was no significant difference between the area of the vessel lumen in the stria vascularis in patients with Ménières disease and that in normal controls. Conclusion: The stria vascularis may be ischemic bilaterally both in bilateral and unilateral Ménières disease. Abnormal findings in the contralateral ears in unilateral Ménières disease reported in previous studies might be related to poor vascularity of the stria vascularis.

Potential cause of positional vertigo in Ménière's disease

Objectives: To compare the incidence of deposits in the semicircular canals between the temporal bones with Ménières disease and normal controls and to investigate the relationship between the incidence of deposits and the symptoms of positional vertigo, often seen in patients with Ménières disease. Study Design: Retrospective histopathologic human temporal bone study. Methods: Twenty-two temporal bones from 11 patients with bilateral Ménières disease, 28 from 14 with unilateral and 50 age-matched normal temporal bones from 30 individuals were histopathologically examined. Medical records were reviewed for clinical history of positional vertigo and duration of disease. Results: Significant differences were found in the incidence of cupular and free-floating deposits in the posterior semicircular canals between temporal bones with and without Ménières disease. The incidence of free-floating deposits in the lateral semicircular canals was significantly higher in cases with unilateral Ménières disease compared with controls. The incidence of these deposits was associated with the duration of disease rather than with aging. All 5 patients with positional vertigo (3 of 11 patients of bilateral Ménières disease and 2 of 14 of unilateral) had free-floating deposits in at least 1 semicircular canal. Conclusion: Our findings suggest a possible causative relationship between cupular and free-floating deposits in the semicircular canals and the symptom of positional vertigo in patients with Ménières disease.

Posterior semicircular canal dehiscence: a histopathologic human temporal bone study.

Background: Posterior semicircular canal dehiscence has been shown to cause ear symptoms. Objective: To evaluate the incidence of dehiscence of the posterior semicircular canal, thin bone overlying the posterior semicircular canal, and the normal development of the distance between the posterior semicircular canal and posterior cranial fossa. Methods: The shortest distance between the posterior semicircular canal and posterior cranial fossa was measured in 1,051 adult human temporal bones (557 cases), and temporal bones with a distance less than 0.1 mm were evaluated. The shortest distance also was measured in 4 fetal temporal bones (2 cases) and 110 temporal bones from children. Results: Of the 1,051 temporal bones, 23 temporal bones (2.2%) had a distance less than 0.1 mm between the posterior semicircular canal and posterior cranial fossa. Two temporal bones (0.2%) had posterior semicircular canal dehiscence, and 2 temporal bones had microfractures in the thin bone; however, related clinical symptoms were not confirmed. In children, the distance between the posterior semicircular canal and the posterior cranial fossa increased with age (&rgr; = 0.68, p < 0.01). Conclusion: The histopathologic incidence of posterior semicircular canal dehiscence was lower than the previous radiographic reports. The dehiscence of the posterior semicircular canal may be due to a developmental anomaly. In our study, none of the cases with a distance less than 0.1 mm had apparent symptoms related to canal dehiscence syndrome. Other factors, in addition to thinning of the bone, may be required to cause the clinical manifestations.

Expression of inflammatory mediators in the otitis media induced by Helicobacter pylori antigen in mice

Helicobacter pylori is a Gram‐negative bacterium that is recognized as one of the key factors in gastric diseases such as gastritis, peptic ulcer and gastric cancer. Recent studies have shown relationships between H. pylori and extra‐digestive diseases, and the presence of H. pylori in the middle ear and upper respiratory tract has been reported. However, the role of H. pylori in middle ear disease remains unclear. The present study demonstrated that H. pylori whole‐cell protein directly induces macrophage migration inhibitory factor, macrophage inflammatory protein 2, interleukin 1β and tumor necrosis factor α in middle ear epithelium in mice, and severe proliferation of inflammatory cells was observed in middle ear cavity inoculated with H. pylori whole‐cell protein. In addition, trans‐tympanic injection of macrophage migration inhibitory factor up‐regulated expression of macrophage inflammatory protein 2 in the middle ear. These findings indicate that H. pylori infection causes immunological inflammation in middle ear epithelium, and H. pylori may play a significant role in otitis media.

Vascular findings in the facial nerve canal in human temporal bones with diabetes mellitus.

Objective: To identify pathological changes to vessels in the facial nerve canal among patients with diabetes mellitus. Design: Histopathologic human temporal bone study. Subject: This study examined 26 temporal bones from 13 patients with type 1 diabetes mellitus and 40 temporal bones from 20 patients with type 2 diabetes mellitus. Temporal bones from patients with type 2 diabetes mellitus were divided into 2 groups according to the method of diabetes management: insulin (n = 11) and oral hypoglycemic agents (n = 9). For the control groups, 16 age-matched normal temporal bones from 11 subjects were recruited for type 1 diabetes mellitus and 11 age-matched normal temporal bones from 8 subjects were recruited for type 2 diabetes mellitus. Main Outcome Measures: Thicknesses of vessel walls in the labyrinthine, tympanic, and mastoid portions of the facial nerve canal were examined under light microscopy. Results: Vessel walls for all portions of the facial nerve canal were significantly thicker in diabetic patients than in normal controls for both types 1 and 2 diabetes. In type 2 diabetic patients, vessel wall thickness was significantly greater in patients treated with insulin therapy than in patients treated via oral hypoglycemic agents. Conclusion: The facial nerve in patients with diabetes mellitus is ischemic compared with normal controls. These findings suggest a histologic basis for the high incidence and difficulty in achieving improvement of facial nerve palsy in patients with diabetes mellitus.

Peripheral Vestibular System in Down Syndrome Quantitative Assessment of Vestibular Histopathology

Objective. To evaluate the maturity of the peripheral vestibular system in Down syndrome by examining the number of Scarpa’s ganglion cells and the density of vestibular hair cells. Study Design. Case-control study using human temporal bones. Setting. Tertiary academic center, otopathology laboratory. Subjects and Methods. Sixteen temporal bones from 8 patients with Down syndrome and 15 control temporal bones from 8 individuals with no history of otologic disease were selected. Hypoplasia of the lateral semicircular canal (LSC) and vestibule was investigated by measuring the dimensions of the structures. Scarpa’s ganglion cells were counted under light microscopy. The vestibular hair cells were counted in the LSC crista and the utricular and saccular maculae under differential interference contrast (Nomarski) microscopy and expressed as density. Results. The patients with Down syndrome were divided into 2 groups: with and without LSC hypoplasia. The number of Scarpa’s ganglion cells and the density of vestibular hair cells were significantly smaller in both groups of patients with Down syndrome than in the control group. There was no significant difference in the number of Scarpa’s ganglion cells or the density of vestibular hair cells between the groups with and without LSC hypoplasia. Conclusion. The peripheral vestibular system, including Scarpa’s ganglion cells and vestibular hair cells, is hypoplastic irrespective of the vestibular malformation in Down syndrome.

Mucormycosis of the temporal bone.

This is a case of a 45-year-old Caucasian male with acute myelogenous leukemia. He received several courses of chemotherapy but never achieved more than a partial remission. His terminal admission was for central nervous system leukemia and blast crisis. Hewas treatedwith brain irradiation, intrathecal injection of methotrexate, and peripheral blood leukapheresis. The patient initially responded satisfactorily, but 3 weeks after admission, he began to complain of pain above his left eye, spiking fevers and neurologic complaints. A sinus x-ray taken at that time showed an acute frontal sinusitis. Despite aggressive local measures consisting of nasal suction and drainage, as well as intravenous administration of antibiotics, he ran a downhill course and died. The cause of death was thought to be meningitis secondary to the frontal sinusitis. Autopsy findings showed the typical rhinocerebral formof zygomycosis. Fungal invasion included the nasal sinuses, penetration of the cribriform plate, and extension into the meninges of the inferior surface of the frontal lobes. The acute onset of neurologic problems was undoubtedly due to the fact that he had mucor meningoencephalitis.