Accumulation of SNAP25 in mouse gustatory and somatosensory cortices in response to food and chemical stimulation.

Food intake stimuli, including taste, somatosensory, and tactile stimuli, are received by receptors in the oral cavity, and this information is then transferred to the cerebral cortex. Signals from recently ingested food during the weaning period can affect synaptic transmission, resulting in biochemical changes in the cerebral cortex that modify gustatory and somatosensory nervous system plasticity. In this study, we investigated the expression patterns of molecular markers in mouse gustatory and somatosensory cortices during the weaning period. The expression of synaptosomal-associated protein 25 (SNAP25), a component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, was increased in the insular and somatosensory cortices at postnatal week 3 compared to postnatal week 2. Additionally, SNAP25 protein in the cerebral cortex accumulated in weaning mice fed solid food but not in mice fed only mother's milk at the weaning stage. Chemical stimulation by saccharin or capsaicin at the weaning stage also increased SNAP25 immunoreactivity in the insular or somatosensory cortical area, respectively. These results suggest that recently ingested chemical signals in the oral cavity during weaning increase the accumulation of SNAP25 in the gustatory and somatosensory cortices and promote neural plasticity during the development of the gustatory and somatosensory nervous systems.

Simple underlay myringoplasty.

OBJECTIVE: To introduce simple underlay myringoplasty which is widely performed in Japan. PATIENTS: 391 ears with perforated eardrum underwent simple underlay myringoplasty from 2000 to 2004, and which were followed up for more than six months after surgery. METHODS: After removing the margin of the perforation by a transcanal approach under local anaesthesia, a connective tissue graft was inserted through the perforation and lifted to contact the edge. Fibrin glue was dropped on the contact area. There was no packing in the canal or in the middle-ear cavity. If the perforation remained, re-closure was attempted using the patient's frozen tissue. RESULTS: The rate of closure after the initial attempt was 304/391 (77.7 per cent), and that after re-closure for unsuccessful cases was 70/87 (80.5 per cent). The overall rate was 374/391 (95.7 per cent). There were no serious complications such as sensorineural hearing loss. CONCLUSIONS: Simple underlay myringoplasty is a simple and minimally invasive procedure employing fibrin glue and has led to a high closure rate of the eardrum.

Mutation at codon 130 in hepatitis B virus (HBV) core region increases markedly during acute exacerbation of hepatitis in chronic HBV carriers.

Mutations within T-cell or B-cell epitopes are suggested to have some influence on the clinical course of chronic hepatitis B virus (HBV) infection. To investigate the relationship between liver cell injury and heterogeneity of the HBV core gene, we focused on the sequence of codon 130, which is located on both T- and B-cell epitopes, and serially analyzed the proportion of mutant virus (core130Thr) to wild-type virus (core130Pro) during the exacerbation of chronic hepatitis B. Sera obtained serially from five HBV carriers who had exacerbation of hepatitis, and three asymptomatic HBV carriers (ASCs) with persistently normal serum aminotransferase (ALT) values were studied, using the restriction fragment length polymorphism (RFLP) method. Core130Pro predominated in the sera in the remission state, but core130Thr increased markedly in parallel with ALT elevation and decreased again after the ALT peak, followed by the predominance of core130Pro, in all the five patients. In one patient, the ratio of core130Thr/core130Pro (Thr/Pro) was more than 70% at the ALT peak. On the other hand, in sera from the three ASCs core130Pro always predominated, and no divergence was identified in the ratio of Thr/Pro. Our data suggest that codon 130 is one of the most important immunogenic regions in the HBV core gene and that elevation of Thr/Pro could be the result of immune selection.

Properties of hepatitis B virus genome recovered from Vietnamese patients with fulminant hepatitis in comparison with those of acute hepatitis.

Among the many mutations found in the hepatitis B virus (HBV) genome, some have been associated with fulminant hepatitis, as exemplified by precore-defective mutations. The aim of this study was to determine whether such mutations also are found in Vietnamese cases of fulminant hepatitis B. The full-genome nucleotide sequence of HBV in three patients with fulminant hepatitis (F-2, F-3, and F-6) and one with acute hepatitis (A-3), who were admitted to Cho Ray Hospital, Ho Chi Minh City, Vietnam was ascertained. Additionally, two patients with fulminant hepatitis (F-1 and F-7) and three with acute hepatitis (A-1, A-2, and A-5) were examined only for the precore/core region of HBV. Remarkably, the nonsense mutation at precore codon 28 (Trp82Stop) was found in four of the five patients with fulminant hepatitis, while all the acute hepatitis patients harbored wild type (one had a mixture of wild and mutant types). The missense mutations within the core region, Ile97Leu and Pro130Ile/Thr/Ser, were also remarkable in fulminant hepatitis. Only F-2 was free from these precore/core mutations, but F-2 was unique in that it possessed a chimeric genotype: it could be classified into genotype C as a whole, but its X region was of genotype B, like the other four fulminant hepatitis isolates (F-1, F-3, F-6, and F-7). The codon 41 of the X protein was Pro in all three fulminant hepatitis cases examined for this region, while it was Ser in the wild-type isolates of genotype B. Of note as negative data, the mutations C1653T and T1753M of the enhancer II (Enh II) and A1762T and G1764A of the precore/core promoter regions, once reported to be relevant to severe or fulminant hepatitis, were not found in the present cases. The results with the Vietnamese cases of fulminant hepatitis corroborated results of previous studies with respect to the mutations Trp28Stop of precore and Ile97Leu and Pro130Ile/Thr/Ser of core, but not for the mutations within Enh II and precore/core promoter region. Whether the Ser41Pro mutation in the X region of genotype B HBV is Vietnam-specific or disease-specific deserves further investigation.

[Neuroimaging findings of hemiconvulsions, hemiplegia, epilepsy (HHE) syndrome].

A 32-year-old man with hemiconvulsions, hemiplegia, epilepsy (HHE) syndrome is described. He was well developed with a normal pregnancy and delivery, but at age 10 months, he had status epilepticus during a febrile illness. Thereafter, he was noted to have left hemiparesis and mental retardation with recurrent hemiconvulsions. Magnetic resonance (MR) images showed atrophy and degeneration of the right cerebral cortex and white matter, homolateral thalamus, caudate nucleus, and hippocampus, with hyperintensities in both T2-weighted (TR/2200, TE/90) and proton (TR/2200, TE/30) images. There were also slight bilateral cerebellar atrophies. Quantitative single photon emission computed tomographic (SPECT) images using technetium-99m-ethyl cysteinate dimer (99mTc-ECD) revealed markedly reduced cerebral blood flow (CBF) in the right cerebral hemisphere, homolateral thalamus, caudate nucleus and bilateral cerebellum. Bilateral putamen and the medial occipital lobe showed normal findings on MR images and normal regional CBF in SPECT images. We suppose these selective neuronal injures in this case of HHE syndrome will be mainly due to histotoxic factors in epileptic brain damage.

Sound localization for a virtual sound source in cases of chronic otitis media.

Sound localization in subjects with chronic otitis media (COM) was examined before and soon after ear surgery by means of virtual sound presented by headphones, sound being synthesized based on the head-related transfer functions (HRTFs) in a normal subject. The localization ability in COM patients was usually worse than that in normal subjects, but was better than expected when compared with cases of acute loss. On the other hand, the effects of hearing improvement on localization ability observed in COM patients were smaller than those of simulated acute hearing loss achieved by earplugs in normal subjects. This seems to suggest that the localization cues in patients with chronic hearing loss are different from those under normal conditions.

Interferon-alpha-induced thyroid dysfunction in patients with chronic active hepatitis C: a transient, reversible and self-limited dysfunction.

To survey the prognoses of interferon-alpha (IFNalpha)-induced thyroid dysfunction, a total of 100 patients (49 males and 51 females) with biopsy-proven chronic active hepatitis C were studied. Either during or after IFNalpha therapy, 29 patients (33.7%) revealed suppression/elevation of thyroid stimulating hormone (TSH) or both, transient thyrotoxicosis (TSH less than 0.1 microU/ml) or transient hypothyroidism (TSH 5.0-190.95 microU/ml). However, the thyroid function normalized without supplementation of the thyroid hormone in the follow-up period. In the same period, one of the 14 control patients (7.1%) developed thyroid dysfunction. Thyroid abnormalities developed significantly more in patients with IFNalpha therapy than in those without IFNalpha therapy. The findings suggest that the occult autoimmune disorder becomes overt with IFNalpha treatment in patients with pre-existent autoimmune thyroid disease. IFNalpha-induced thyroid dysfunction is transient, reversible and self-limited. It is not necessary to discontinue IFNalpha therapy when thyroid dysfunction develops.

Serum androgen levels in hyperthyroid women.

Thyroid hormone is known to affect androgen metabolism, however, there are few studies in which alterations of androgen metabolism are simultaneously examined in patients with clinical thyroid disorders. In this study, we investigated the alterations of thyroid hormone and androgens before and during treatment in patients with hyperthyroidism. Fifteen female patients with hyperthyroidism due to Graves' disease were studied. From these patients, blood samples were obtained before treatment and at 1 month (M), 2M, 3M, 4M and 6M after beginning of treatment. Concentrations of free T4(FT4), free T3(FT3), testosterone (T), androstenedione (delta 4A), dihydrotestosterone (DHT), 5 alpha-androstane-3 alpha, 17 beta-diol(3 alpha-diol) and androsterone (AD) and sex hormone binding globulin (SHBG) were measured by radioimmunoassays (RIAs) or immunoradiometric assay (IRMA). As normal controls, ten healthy women were also studied. Before treatment concentrations of DHT (mean +/- SD: 3.35 +/- 0.78 nmol/L), 3 alpha-diol (0.78 +/- 0.11 nmol/L), AD (6.73 +/- 0.64 nmol/L) and SHBG (184.9 +/- 68.1 nmol/L) were significantly elevated compared with those of normal controls. T and delta 4A levels were not significantly different from normal values. DHT/T ratio indicating 5 alpha-reductase activity was 4.62 +/- 2.55 and significantly higher than that in normal controls. At 2 months after beginning of treatment with anti-thyroid drugs, thyroid function (FT4 and FT3) became normal and at 3 months after beginning of treatment, DHT, 3 alpha-diol, AD and DHT/T ratio decreased to normal range. SHBG level was gradually decreased, however still higher than that of the normal control group at 6 months after beginning of treatment. There was a time lag in recovery between serum androgen levels and SHBG level.

[Congenital cholesteatomas in Japanese--forty from our experience and fifty-five from a survey of the Japanese literature].

To determine the locations of congenital cholesteatomas and to elucidate the relationship between ossicular anomalies and congenital cholesteatomas, cholesteatomas from our patients and those reported in the Japanese literature were investigated. We analyzed 40 ears with congenital cholesteatomas (38 patients) experienced by us during the past 9 years. Our criteria of congenital cholesteatoma were as follows: 1. The tympanic membrane manifests neither retraction, perforation, nor granulation, 2. There is no continuity between the tympanic membrane and the matrix of a cholesteatoma. Twenty patients with past histories of otitis media were included. Thirty-three patients (87%) were males and 2 had bilateral congenital cholesteatomas. The ages of the patients ranged from 2 to 46 years (mean: 10.7). A survey of the Japanese literature revealed 55 additional cases of congenital cholesteatoma reported by others.

Hemorrhage and abnormal veins in acoustic neurinoma: MR findings.

We reviewed the MR imaging findings of 57 acoustic neurinomas which were verified at surgery or diagnosed on the basis of neuroradiological and neurootological data. Two uncommon MR findings of acoustic neurinoma were found. First, hypointense areas were observed on T2-weighted images in five of the 12 tumors larger than 25 mm in diameter. These hypointense areas represented hemosiderin deposition secondary to occult intratumoral hemorrhage. Second, curvilinear or round signal voids were noted at the periphery of 11 large or medium-sized tumors, and these corresponded to "abnormal veins" seen on angiographic studies.

Selegiline (L-deprenyl) and L-dopa treatment of Parkinson's disease: a double-blind trial.

To confirm the clinical utility of selegiline (L-deprenyl), a selective inhibitor of monoamine oxidase B, as an anti-Parkinson's disease (PD) agent, the first Japanese multi-center, double-blind comparative study of this drug was conducted. The subjects were patients who had responded poorly or suffered with other problems related to L-dopa treatment. A total of 112 patients in two groups, one given selegiline at a dose of 7.5 mg/day (Group D, n = 60) and another given a placebo (Group P, n = 52), were compared over an 8-week treatment period. The percentage patients showing "moderate improvement" or better was 34.5% in Group D, while that in Group P was 11.5% (P < 0.01). In the assessment of overall safety, 66.7% in Group D showed no adverse reactions, which was not significantly different from the result of 78.9% for Group P.

Immunopathological features of palatine tonsil characteristic of IgA nephropathy: IgA1 localization in follicular dendritic cells.

IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN, and in some cases tonsillectomy is effective for the treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or progressive events to generate nephritogenic immune complexes in IgAN. In this study we focused on the analysis of immunopathological features of the palatine tonsil characteristic of IgAN patients by using an immunohistochemical technique. The IgA1 subclass was demonstrated in follicular dendritic cells (FDC) of the tonsil of IgAN patients, but not in FDC of non-IgAN controls. On the other hand, IgA2, IgG, IgM and C3 did not show any differences in distribution between the two groups. Moreover, the expression of decay-accelerating factor (DAF), an inhibitor of homologous complement activation, and transforming growth factor-beta 1 (TGF-beta 1), an inducer of antibody-producing cells to IgA class switching, in FDC and interdigitating dendritic cells of the tonsil, respectively, which was also clarified in this study for the first time, was found to be identically distributed in the two groups. These findings may support the idea that IgA1, possibly in an immune complex form, is trapped by FDC and plays an important role in the persistent activation of particular B cell repertoires responsible for the onset and/or progression of IgAN.

[A case of a right bronchial foreign body (rice cake)].

We had a case of a bronchial foreign body (rice cake). A 73-year-old male with severe dyspnea was taken by emergency car. His right breathing sound was very weak, but chest X-ray showed no changes. We diagnosed it as right bronchial foreign body and we could endoscopically remove the foreign body with basket-forcep successfully. We could save his life.

Reinforcing aerosol cisplatin for radiotherapy of laryngeal cancer.

To attain its increased tumor concentration and to avert its systemic adverse effects, aerosol cisplatin (CDDP) was incorporated into radiotherapy (RT) of laryngeal cancer. Nine patients were asked to inhale the aerosol following each RT session. Their clinical tumor response was favorable, and histopathologic survey in selected cases revealed elimination of viable cancer cells. However limited, there have been no reports of cancer recurrence yet. This reinforcing plan of aerosol CDDP for RT bleomycin would certainly offer a better way of treating laryngeal cancer, and probably those malignancies facing the nasopharyngobronchial airway as well.

[Upper and lower airway diseases in children with persistent cough].

Persistent cough is a frequent and frustrating problem in the pediatric field. One hundred and seventy two children presenting with persistent cough for longer than 2 weeks were evaluated by both otolaryngologists and pediatricians. One hundred and twenty nine cases (75%) were found to have lower airway diseases, of which bronchial asthma, bronchitis and pneumonia, in that order, were the most common. One hundred and forty two cases (82%) had sinusitis, in 34 cases of which no causative diseases except sinusitis were found to be responsible for the persistent cough. Sinusitis was found in 90% of patients with pneumonia, 81% of those with bronchitis and 65% of those with poorly controlled asthma cases. These results revealed that sinusitis is an important causative factor for persistent cough in children. All the patients with pneumonia and bronchitis were cured by antibiotic administration for 2 weeks, whereas conservative treatment of sinusitis for as long as 6 months was less satisfactory resulting in only 60% cure, 18% improvement and 22% without improvement. In cases with sinusitis and lower airway diseases, continuous treatment for sinusitis is necessary even after treatment of the lower airway diseases has been completed.

Iodide induces transforming growth factor beta 1 (TGF-beta 1) mRNA in sheep thyroid cells.

We examined TGF-beta mRNA levels in primary sheep thyroid cell cultures to determine whether the inhibitory effects of iodide on thyroid cells could be explained by an induction of TGF-beta mRNA and if this induction was mediated by iodine organification. Thyroid cells were incubated with TSH and five additives (insulin, somatostatin, growth hormone, transferrin, and glycyl-L-histidyl-L-lysin) for 2-3 weeks and then were exposed to sodium iodide (NaI) or 1-methylimidazole-2-thiol (methimazole, MMI), or both for 72 h. Iodide at 10(-6) M and 10(-4) M significantly increased the amount of TGF-beta mRNA as determined by Northern blot analysis with a rat TGF-beta 1 cDNA probe. This increase in TGF-beta 1 mRNA was abolished by the addition of methimazole, an inhibitor of organification. These data indicate that the effects of iodide on thyroid growth and function may be mediated by a process that involves organification of iodide and increases in TGF-beta 1 mRNA levels.

Bone destruction mechanisms in chronic otitis media with cholesteatoma: specific production by cholesteatoma tissue in culture of bone-resorbing activity attributable to interleukin-1 alpha.

To clarify specific mechanisms underlying cholesteatoma-induced bone destruction, surgical specimens of middle ear inflammatory granulation tissue with or without cholesteatoma were maintained in vitro and the bone-resorbing activity in their culture supernatants was analyzed by means of calcium release from mouse calvaria. Almost the same levels of bone-resorbing activity and prostaglandin (PG) E2 were found in the supernatants of both types of tissue. By contrast, aural polyp tissue yielded hardly any such activity or PGE2. Under the influence of indomethacin, however, only tissue with cholesteatoma produced considerable bone resorption activity, whereas PGE2 production was suppressed completely. Such activity in the cholesteatoma culture supernatant was not due to contamination of endotoxin and proved to be blocked by the introduction of anti-interleukin (IL)-1 alpha antibody into the calvarial assay system. Anti-IL-1 beta antibody had no effect on such activity. Interleukin-1 alpha was detected only in cholesteatoma tissue culture supernatants by means of enzyme-linked immunosorbent assay and by bioassay. These data suggest that the bone destruction in otitis media with cholesteatoma may be attributed to IL-1 alpha in addition to PGE2.

Effect of external auditory canal pressure upon the hearing threshold in patients with Menière's disease.

Fluctuation of hearing at low frequencies is one of the most characteristic findings in Meniere's disease and seems to be a phenomenon closely related to changes of endolymphatic pressure and volume. In the present study, pressure was applied to the external auditory canal of patients with Meniere's disease, and the effect on the bone conduction threshold was examined at times of depressed and improved hearing. In more than half of these cases, it was found that the pressure effect was marked at the time of improved hearing acuity, but not at the time of depressed hearing. This effect was also confirmed in more objective experiments with guinea pigs. It is concluded that the fluctuation of hearing in Meniere's disease seems to be a phenomenon accompanying the endolymphatic pressure change in the scala media.

[Gellé test in patients of Menière's disease and fluctuating low tone hearing loss].

The threshold shift at 500 Hz bone conduction under positive and negative static pressure of 400 mmH2O applied to the external auditory canal was examined in 20 patients of Meniere's disease with fluctuating low tone hearing loss, 21 patients of sensorineural hearing loss without fluctuating and 24 normal controls. In contrast to the 10 to 15 dB threshold shift in the latter two groups (non-fluctuating group, 14.8 +/- 5.1 dB at positive and 11.1 +/- 5.7 dB at negative; normal controls, 13.6 +/- 5.4 dB at positive and 9.3 +/- 5.3 dB at negative), the former showed a significantly smaller shift (3.2 +/- 6.1 dB at positive and 2.3 +/- 4.5 dB at negative) while hearing was depressed. However, when the hearing was improved, the pressure effect became greater even in the former group (11.3 +/- 5.3 dB at positive and 9.1 +/- 4.8 dB at negative). To understand further details of these phenomena, we performed electrophysiological animal experiments. Through a small hole made on the guinea pig's cochlear bony wall, 300 mmH2O pressure was applied to the scala tympani and the threshold of 500 Hz CM was examined in both endolymphatic sac obliterated ears and non-obliterated ears. In 14 non-obliterated ears 21.1 +/- 5.1 dB threshold shift was recorded, whereas it was only 1.6 +/- 2.6 dB in 9 obliterated ears at 4-6th postoperative days. These results seem to reflect that the endolymphatic pressure is great during the early stage of hydrops.(ABSTRACT TRUNCATED AT 250 WORDS)