Local increase in IgE and class switch recombination to IgE in nasal polyps in chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is generally characterized by local Th2 inflammation and is categorized into two subtypes in Japan: eosinophilic chronic rhinosinusitis (similar to chronic rhinosinusitis with nasal polyps in western countries) and non-eosinophilic chronic rhinosinusitis (characterized by Th1-dominant inflammation). OBJECTIVE: To investigate local IgE production and class switch recombination to IgE in these two subtypes of chronic rhinosinusitis with nasal polyps. METHODS: The identity of IgE-positive cells was determined using double-immunofluorescent staining for IgE and cell-type-specific molecular markers. To investigate the local class switch recombination to IgE and IgE synthesis in the mucosa, we performed real-time polymerase chain reaction to examine the mRNA expression of Th2 cytokines and class-switch-related molecules, including IL-4, IL-5, IL-13, ε germline gene transcripts, IgE mature transcript, IgG mature transcript, RAG1, RAG2 and activation-induced cytidine deaminase in eosinophilic polyps, non-eosinophilic polyps and controls. RESULTS: The concentrations of total IgE and number of IgE-positive cells were significantly higher in the eosinophilic polyps compared with control and non-eosinophilic polyps. IgE-positive cells were predominantly mast cells in eosinophilic polyps and significantly correlated with the number of FcεR1-positive cells in the subepithelial layer. IL-5 and IL-13 mRNA and ε germline gene transcripts expression levels were significantly higher in eosinophilic polyps compared with control and non-eosinophilic polyps. In contrast, the number of plasma cells and the expression of IgG mature transcripts were increased in non-eosinophilic polyps compared with eosinophilic polyps. RAG2 mRNA was significantly increased in both eosinophilic and non-eosinophilic polyps compared with control mucosa. CONCLUSION AND CLINICAL RELEVANCE: The current study suggests local class switching to IgE, production of IgE and IgE localization to the surface of mast cells in eosinophilic chronic rhinosinusitis in the Japanese population. The difference in the IgE-related profiles between eosinophilic chronic rhinosinusitis and non-eosinophilic chronic rhinosinusitis suggests heterogeneity in the pathogenesis of chronic rhinosinusitis with nasal polyps.

Click- and short tone burst-evoked myogenic potentials in cerebellopontine angle tumors.

We report results of vestibular-evoked myogenic potentials (VEMPs) in patients with cerebellopontine angle tumors and compare results obtained using clicks with those obtained using 500 Hz short tone bursts (STB). We reviewed the records of 87 patients with cerebellopontine angle tumors. Clicks (0.1 ms, 95 dB nHL) were presented to all patients and STB (500 Hz, rise/fall time 1 ms, plateau time 2 ms, 95 dB nHL) were presented to 27 patients. Click-evoked VEMPs were abnormal in 69/87 patients (79%; no response in 55 patients, decreased response in 14 patients, normal response in 18 patients). STB-evoked VEMPs were abnormal in 22/27 patients (82%; no response in 18 patients, decreased response in 4 patients, normal response in 5 patients). Click- and STB-evoked VEMPs were identical in 23/27 patients (85%). Two patients showed normal STB-evoked VEMPs and decreased click- evoked VEMPs, and 2 patients showed decreased STB-evoked VEMPs and absent click- evoked VEMPs. These results confirm our previous study in a small number of patients. Vestibular afferents seem to respond better to 500 Hz STBs than to clicks.

Auditory brainstem response and temporal bone pathology findings in a brain-dead infant.

The criteria for assessing adult brain death have been already established, but those for infant brain death have not been yet established in Japan. We report auditory brainstem response (ABR) and postmortem pathology of the temporal bone and brain of a brain-dead 9-month-old female. During the comatose state, her ABR showed only waves I and II bilaterally. Autopsy revealed the presence of a left cerebellar astrocytoma, herniation and anoxic encephalopathy. The pathological examination of the temporal bone revealed the destruction of the inner ear particularly on the left side. In the auditory pathway of brain-dead patients, degeneration occurs first in the cerebrum, followed by the cochlear nerve. Thus, ABR is one of the useful means to assess brain death even in infants.

Analysis of aluminum hydroxyphosphate vaccine adjuvants by (27)Al MAS NMR.

The present study explores the use of (27)Al magic-angle-spinning (MAS) NMR for the characterization of aluminum hydroxyphosphate adjuvants. Adjuvants were prepared by two different methods: batch-precipitation and precipitation at constant pH, using a wide range of different conditions. The adjuvant compositions showed no evident stoichiometric restrictions and varied as a function of the precipitation conditions. All the aluminum hydroxyphosphate adjuvants were found by (27)Al MAS NMR to contain both tetrahedrally and octahedrally coordinated aluminum. The octahedral form was always predominant. The chemical shifts corresponding to octahedral aluminum were at values intermediate between that of aluminum hydroxide (9 ppm) and those of phosphate-containing aluminum minerals such as variscite (-9 ppm) and varied with the phosphate content of the adjuvant. This was true even for adjuvants precipitated above pH 6 indicating that the phosphate is incorporated into the bulk solid phase contrary to predictions in the literature. Aside from the presence of tetrahedral and octahedral aluminum, there was no evidence in any of the adjuvants of distinct, structurally defined phases indicating that the adjuvants are not mixtures of distinct phases which differ significantly in the number of phosphorus atoms in the next-nearest-neighbor (NNN) position to aluminum.

[The actual conditions of patients with intractable diseases in Hiroshima Prefecture].

All 3,515 patients of intractable diseases who received medical benefits in Hiroshima prefecture were surveyed to determine actual conditions of daily life while being treated. This is the first study in Japan, which has looked at daily life of all patients of intractable diseases at the level of a whole prefecture. Effective collection rate of the questionnaire was 78.8% (2,768 cases). The results are summarized as follows: 1) Many patients and their families wish to be treated at home, with the more severely impaired patients expressing a greater need for home care. 2) Large regional differences were seen in required travel time to visit the hospital, and in the percentage of patients and their families who expressed a desire for medical specialists in intractable diseases for their region. 3) While income of families of the severely impaired patient was generally low, their medical payment burden was heavy. In addition families of patients were heavily burdened physically and mentally. The tasks that lie ahead in the care of patients of intractable diseases would be home care assistance, correction of regional differences, and financial aid for severely impaired patients.

An endocrinological study of persistent pubertal macromastia.

We performed an endocrinological study on three males with persistent pubertal macromastia. The blood testosterone (T) level in these patients was either elevated or at the upper normal limit, estrone (E1) and estradiol (E2) levels were high, and T/E1 and T/E2 ratios were decreased. Persistence of low T/E1 and T/E2 ratios was thought to be the cause of the macromastia. Results of therapy using drugs (cyproterone acetate, tamoxifen citrate, danazol, and clomiphene citrate) were unsatisfactory. Persistent pubertal macromastia is an extreme condition of physiological pubertal gynecomastia, a transient phenomenon in more than half of pubertal males. It is a pathological condition characterized by a great degree of breast enlargement and abnormal endocrinological findings, and its clinical course and treatment are different from those of physiological pubertal gynecomastia.

[Behavioral pharmacological and electroencephalographic effects of the 5-HT1A partial agonist ipsapirone].

The behavioral and EEG effects of the 5-HT1A partial agonist ipsapirone were investigated to determine its pharmacological characteristics as an anxiolytic drug in rats, mice and rabbits, as compared with those of buspirone and diazepam. 1) The anticonflict effect of ipsapirone was almost equipotent as that of buspirone and less potent than that of diazepam in rats. Ro15-1788 antagonized the anticonflict effect of diazepam, but did not that of ipsapirone. 2) Muricide in midbrain raphe-lesioned and olfactory bulbectomized rats was inhibited by ipsapirone. However, the inhibition of muricide by ipsapirone was attenuated by its repeated administration. 3) The muscle relaxant effects of ipsapirone and buspirone on rotarod performance were less potent than that of diazepam. Ethanol-induced muscle relaxation was markedly potentiated by diazepam, but less potently by ipsapirone and buspirone. 4) The pentetrazol-induced convulsion was dose-dependently antagonized by diazepam, while it was weakly potentiated by ipsapirone and buspirone. 5) The limbic afterdischarges induced by either hippocampal or amygdaloid stimulation in rabbits were markedly inhibited by diazepam. Conversely, ipsapirone and buspirone slightly potentiated afterdischarges. In conclusion, it is suggested that ipsapirone has anxiolytic activities similar to that of buspirone and moderate antimuricidal action. In addition, ipsapirone, like buspirone, is also characterized by its less potent muscle relaxant, alcohol-potentiating and anticonvulsant actions.

Prevalence of antibody to Chlamydia pneumoniae TWAR in japan.

Chlamydia pneumoniae TWAR is a newly recognized Chlamydia species that is a pathogen of respiratory tract infection. To clarify the endemic status of C. pneumoniae in Japan, we evaluated the incidence of C. pneumoniae antibody in 1,330 serum samples (660 from outpatients, 600 from normal individuals, and 70 from cord blood). The antibody titer was determined by a microimmunofluorescence test by using the elementary body of C. pneumoniae TW-183 as the antigen. Immunoglobulin G antibody titers of 1:32 or higher were regarded as evidence of past infection. The detection rate of C. pneumoniae antibody rapidly increased in subjects between the ages of 4 and 7 years, reached 44% in subjects between the ages of 8 and 11 years, and was about 50% in older subjects. The rate did not differ between healthy subjects and outpatients. These results suggest that C. pneumoniae infection is highly endemic in Japan as it is in Western countries. However, the antibody prevalence was high in the low age groups in Japan compared with that in Western countries.

[Prevalence of antibodies to Chlamydia pneumoniae (strain TWAR) and other Chlamydia in Japan].

Chlamydia pneumoniae (Strain TWAR), the new third species of genus Chlamydia, is emerging as an important human respiratory pathogen in Western countries. However, little is known about it in Japan. In this study, 1330 serum samples were tested for seroprevalence of three species of genus Chlamydia including C. pneumoniae in Hiroshima. Microimmunofluorescence test was used to measure serum IgG antibody, and formalin fixed elementary bodies of C. trachomatis, C. psittaci, and C. pneumoniae were used as antigen. Serum titer of 1:32 or greater was considered positive. Seropositive rate of C. pneumoniae began to increase around the 6 month to 3 year old age group and reached 44% in the 8 to 11 year olds. A peak of seroprevalence according to age was around 20 year old, and about half of the adults were seropositive. Outpatients and healthy persons held almost the same seropositive rate. The positive rate in childhood was higher and the peak appeared earlier than some former studies in Western countries. The seropositive rate of C. trachomatis was noted 1-2% in the 6 month-7 year old age group, but no seropositive child was found in the 8-15 year olds. The rate was increased after adolescence and reached 10% in adults. The seroprevalence of C. psittaci was 1%. These data suggest C. pneumoniae is the most prevalent Chlamydia in Japan and as prevalent as in the Western countries.

Conflict behavior and dynamics of monoamines of various brain nuclei in rats.

The present study was an attempt to clarify the role of noradrenaline (NA) and of the 5-hydroxytryptamine (5-HT) system in various nuclei in brain, as a component of a proposed neural circuit in the mediation of conflict behavior and the anticonflict action of anxiolytics. The authors investigated changes in the concentrations of NA, 3-methoxy-4-hydroxyphenylethyleneglycol, 5-HT and 5-hydroxyindoleacetic acid in discrete regions of the brain in rats, in correlation with conflict behavior and also the effects of diazepam and suriclone. Noradrenergic neural activity diminished with a conflict situation, in the frontal cortex, central amygdala, mammillary body and dorsal hippocampus. 5-Hydroxytryptaminergic neural activity increased with a conflict situation in the frontal cortex, central amygdala, basolateral amygdala and medial septum. These changes in the frontal cortex, central amygdala, mammillary body and dorsal hippocampus were not observed when diazepam 20 mg/kg (p.o.) and suriclone 40 mg/kg (p.o.) produced anticonflict action. Suriclone normalized the increased 5-HT-ergic activity in the medial septum. The suppression of NA-ergic and the activation of 5-HT-ergic (except for the mammillary body) neural activity in the frontal cortex, central amygdala, mammillary body and dorsal hippocampus seemed to be linked to the mediation of conflict behavior. The facilitatory and inhibitory action on NA and 5-HT (except for the mammillary body) neurons, respectively, in these regions of the brain, may be involved in mechanisms underlying the anticonflict action of anxiolytics (diazepam or suriclone).

Changes of brain monoamine contents in three models of experimentally induced muricide in rats.

Monoamine levels were measured by high performance liquid chromatography with electrochemical detection in seven brain regions of three models of experimentally-induced muricide (mouse-killing behavior) in rats (bilateral olfactory bulbectomized rats: OB rats, midbrain raphe nuclei lesioned rats: Raphe rats and nucleus accumbens lesioned rats: Acc rats). Noradrenaline (NA) levels in the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), 3,4-dihydroxyphenylacetic acid (DOPAC) levels in LH and homovanillic acid (HVA) levels in the frontal cortex (FC) were increased in all three muricide models. In LH, serotonin (5-HT) levels increased in Acc rats and the 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio was reduced in OB rats. But in VMH an increase in NA level was not accompanied by any changes of other amines in three muricide models except for 5-HT and 5-HIAA in Raphe rats. In the mamillary body (MB), NA level was increased and 5-HIAA/5-HT ratio was decreased in both OB and Acc rats. Monoamine changes in the amygdaloid nuclei were different in three muricide models, suggesting that the role of monoamines in various nuclei of the amygdala may be different in each muricide model. The present findings suggest that both noradrenergic (LH and VMH) and serotonergic function (LH and MB) may play an important role in exhibiting muricide of OB, Raphe and Acc rats, while dopaminergic function (LH and FC) may be related rather to hyperirritability elicited in these three muricide models.