Atsushi Yuta

Increased expression of histamine H1 receptor mRNA in allergic rhinitis

Background Histamine plays an important role in producing nasal symptoms via histamine H1 receptor (H1R) in allergic rhinitis. It is reported that the minimum histamine concentration that induces sneezing is lower in allergic patients than in normal control subjects. Previous studies by binding assay on H1R gave divided results on whether the number of H1Rs is increased in allergic rhinitis or not.

Determination of Cellularly Processed HLA-A2402-Restricted Novel CTL Epitopes Derived from Two Cancer Germ Line Genes, MAGE-A4 and SAGE

Purpose: For identification of CTL epitopes useful for cancer vaccines, it is crucial to determine whether cognate epitopes are presented on the cell surface of target cancer cells through natural processing of endogenous proteins. For this purpose, we tried to use the cellular machinery of both mice and human to define naturally processed CTL epitopes derived from two “cancer germ line” genes, MAGE-A4 and SAGE. Experimental Design: We vaccinated newly produced HLA-A2402 transgenic mice with DNA plasmids encoding target antigens. Following screening of synthesized peptides by splenic CD8+ T cells of vaccinated mice, we selected candidate epitopes bound to HLA-A2402. We then examined whether human CD8+ T cells sensitized with autologous CD4+ PHA blasts transduced by mRNA for the cognate antigens could react with these selected peptides in an HLA-A2402-restricted manner. Results: After DNA vaccination, murine CD8+ T cells recognizing MAGE-A4143-151 or SAGE715-723 in an HLA-A2402-restricted manner became detectable. Human CTLs specific for these two peptides were generated after sensitization of HLA-A2402-positive CD8+ T cells with autologous CD4+ PHA blasts transduced with respective mRNA. CTL clones were cytotoxic toward tumor cell lines expressing HLA-A2402 and cognate genes. Taken together, these CTL epitopes defined in HLA-A24 transgenic mice are also processed and expressed with HLA-A2402 in human cells. The presence of SAGE715-723-specific precursors was observed in HLA-A2402-positive healthy individuals. Conclusions: Two novel HLA-A2402-restricted CTL epitopes, MAGE-A4143-151 and SAGE715-723, were identified. Our approach assisted by cellular machinery of both mice and human could be widely applicable to identify naturally processed CTL epitopes.

Interleukin-8 gene expression in chronic sinusitis

PURPOSE Interleukin-8 (IL-8), a monocyte-derived and macrophage-derived cytokine, displays potent chemotactic activating properties toward neutrophils and thus may contribute to the pathogenesis of chronic sinusitis. The object of this investigation was to show the expression of the IL-8 gene in chronic sinusitis by Northern blot analysis and a reverse transcription-polymerase chain reaction (RT-PCR). MATERIALS AND METHODS For Northern blot analysis, RNAs were extracted from maxillary mucosa and nasal polyps from two patients with chronic sinusitis, respectively, and from the inferior turbinate of a nasal allergy patient. For RT-PCR, RNAs were extracted from 11 patients with chronic sinusitis, 8 patients with allergic rhinitis, and 4 patients with hypertrophic rhinitis. RESULTS Whereas IL-8 mRNA was expressed in the maxillary mucosa, IL-8 transcript was not detected in the inferior turbinate by Northern blot analysis. IL-8 transcripts were detected in 45% of chronic sinusitis RNAs (5/11) and in 50% of allergic rhinitis RNAs (5/10) by RT-PCR. CONCLUSION These data suggest IL-8 may contribute to neutrophil involvement in chronic sinusitis.

Interleukin-8 Gene Expression in Middle Ear Effusions

Interleukin-8 (IL-8), a monocyte- and macrophage-derived cytokine, displays potent chemotactic-activating properties toward neutrophils, and thus may contribute to the pathogenesis of otitis media with effusion (OME). The objective of this investigation was to demonstrate the expression of the IL-8 gene in middle ear effusions (MEEs) of children and adults with OME. Ribonucleic acids (RNAs) were extracted from MEEs from 16 ears of 13 pediatric patients and 12 ears of 12 adult patients with OME. The RNAs were reverse-transcribed and amplified by the polymerase chain reaction. Interleukin-8 transcripts were detected in 75% of both pediatric (12/16) and adult MEEs (9/12). The levels of expression of IL-8 and β-actin messenger RNAs were quantitated. No significant difference was observed in IL-8/β-actin ratios between pediatric MEEs and adult MEEs. These data suggest that IL-8 may contribute to neutrophil involvement in both pediatric and adult OME.

Too young to talk of vertigo

In April, 2003, a previously healthy 5-year-old girl came to our hospital, with vomiting and abdominal pain. She had been vomiting several times an hour, for 8 h; the vomit did not contain blood or bile. Her medical and family histories were unremarkable; growth and developmental milestones were normal. The girl was alert and afebrile; heart rate and blood pressure were normal. General and neurological examination showed no abnormality. We diagnosed gastroenteritis, and prescribed intravenous fl uids. The girl stopped vomiting the next day, and was discharged the day after. However, she subsequently had several similar episodes of illness. On each occasion, she vomited for several hours, was treated with bed rest or intravenous fl uids, and recovered fully within a day; treatment with domperidone was ineff ective. Vomiting was often accompanied by abdominal pain and headache, but not by fever, cough, diarrhoea, or weight loss. Routine blood tests, including concentrations of glucose and ammonia, showed no abnormalities; nor did blood-gas testing. We sometimes found mild ketonuria. We found no abnormalities on electrocardiography, abdominal radiography or ultrasonography, CT of the abdomen and brain, or electroencephalography. We therefore provisionally diagnosed her illness as cyclic vomiting. 13 months after the fi rst episode, the girl’s mother revealed that before vomiting began, the patient often described feeling her head swaying. We surmised that this might be vertigo. Otoscopy showed nothing abnormal. We observed no nystagmus when the patient was at rest; reactive nystagmus was elicted from caloric refl ex testing (with warm and cold water) of the left ear, but not the right ear, implying damage to the semicircular canals of the right ear, or their aff erent nerves. Pure-tone audiometry showed mild sensorineural hearing loss in the right ear (fi gure). Ear-targeted CT showed no abnormalities. We therefore diagnosed Meniere’s disease, according to standard criteria, surmising that perhaps the patient was too young to complain of tinnitus or a sensation of aural fullness. We prescribed isosorbide, an osmotic diuretic; the patient’s vomiting and feeling of dizziness disappeared. A year after treatment started, we noted that her hearing had improved. When last seen, in June, 2008, the patient continued to be free of vomiting and vertigo; she continued to take isosorbide. Meniere’s disease, fi rst described in 1861, is idiopathic endolymphatic hydrops (excess fl uid in the inner ear), causing deafness, tinnitus, and vertigo. The median time of onset is the fourth decade; Meniere’s disease is rare in children. It is also probably underdiagnosed. Children who complain of dizziness tend to be overlooked, perhaps partly because they have diffi culty describing it, and because vaguely defi ned “dizziness” has many possible causes. Therefore, children with Meniere’s disease often present with vomiting—which can easily be misdiagnosed as cyclic vomiting or migraine (including abdominal migraine). Hearing loss sometimes develops after onset of the disease. Audiometry can be useful in identifying the cause of unexplained vomiting or “dizziness”; regrettably, it is not always widely available.

Epidemiological analysis of nasopharyngeal carcinoma in the central region of Japan during the period from 1996 to 2005

OBJECTIVE It has become clear through epidemiological analysis that the incidence of cancers of the lung, liver, colon, and rectum are increasing in Japan every year. However, there have been few epidemiological analyses of nasopharyngeal carcinoma (NPC) in Japan. The aim of this study was to analyze the epidemiology and current incidence of NPC in the Chubu region of Japan during the period from 1996 to 2005. METHODS Takeshita et al. conducted a similar investigation in the Chubu region 10 years ago, and, as a result, this is a comparative study. The Chubu region is the central region of Japanese main island. We researched NPC patients treated in hospitals in each prefecture over a 10-year period (1996-2005) using a questionnaire. RESULTS A total of 525 cases (male:385, female:134, unknown:6) were analyzed epidemiologically, histologically, serologically, and clinically in this study. The incidence per 10(5) population per year was 0.29. For the period of 1986-1995, the age-standardized incidence of NPC was 0.28 per 10(5) persons per year in Takeshitas report. There was no significant difference between the two periods. The ages of the patients ranged from 13 to 90 years. The mean age of was 55.2 years. On the basis of the World Health Organization (WHO) histological criteria, 36% of the patients were classified as WHO I, 27% as WHO II, and 37% as WHO III. Carcinoma was located in the posterosuperior region in 56%, lateral in 41%, and inferior in 3%. Tumor staging showed that 6% to belonged to stage I, 25% to stage II, 31% to stage III, and 38% to stage IV. A neck mass was present in 52% of the patients, ear symptoms in 48%, nasal symptoms in 27%, headaches in 10%, pharyngeal symptoms in 9%, ophthalmologic symptoms in 9%, and cranial neurological symptoms in 9%. The positive rates of serum titers of the antibodies to Epstein-Barr virus (EBV)-related antigens were calculated. The positive rate of anti-EBV-viral capsid antigen (VCA) immunoglobulin (Ig) G titers was 58.6%, that of anti-EBV-VCA IgA titers was 53.6%, and that of EBNA was 81%. The five-year survival rate for all patients was 67.6%, and that for those in stage I, II, III, and IV was 75%, 84%, 69%, and 53%, respectively. The five-year survival rate for stage IV was significantly lower than those for the other stages (P<0.05). CONCLUSION The age-standardized annual incidence of NPC in our survey was 0.29 per 10(5) persons per year, being relatively low and stable.

Non-recurrent inferior laryngeal nerve with multiple arterial abnormalities.

Non-recurrent inferior laryngeal nerve (NRILN) is a rare embryologic anomaly that can increase the risk of injury during thyroid surgery. Although the association between the NRILN and an aberrant right subclavian artery has been reported, to date there have been no reports describing cases of NRILN with multiple vascular abnormalities. A 60-year-old man with papillary thyroid carcinoma and a history of right internal carotid artery occlusion by thrombosis was examined with magnetic resonance angiography (MRA). The right NRILN was found during a total thyroidectomy with surrounding lymph node dissection. MRA revealed an aberrant right subclavian artery and aplasia of the bilateral posterior communicating arteries composing the circle of Willis. This is the first clinical report demonstrating NRILN with multiple vascular abnormalities. Patients with NRILN must be examined for vascular anomalies and associated lesions such as aneurysms and thromboembolism.

MUC2 mucin gene expression in the nose and maxillary sinus

PURPOSE The MUC2 gene encodes the core protein of a mucin expressed in the intestine and lower airway. The purpose of this study is to examine if the MUC2 gene is expressed in the nose and maxillary sinus. MATERIALS AND METHODS A Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were performed. For the Northern blot analysis, RNAs were extracted from maxillary mucosae and nasal polyps of patients with chronic sinusitis and from the inferior turbinates of a nasal allergy patient. For RT-PCR, RNAs were extracted from 10 patients with chronic sinusitis, 4 patients with allergic rhinitis, 2 patients with hypertrophic rhinitis, and 6 volunteers with normal nasal mucosa. RESULTS Hybridization of the Northern blot with SMUC41 (a part of MUC2) cDNA probe showed clear bands in 2 of the 3 samples. In RT-PCR, the first round of amplification (35 cycles) failed to give any bands, but the additional 30 cycles with internal primers gave bands in 6 of 22 samples. CONCLUSIONS These results indicate that MUC2 mucin gene is expressed in the nose and paranasal sinus. This two-round RT-PCR method will be useful for analysis of MUC2 mucin gene expression using relatively small amount of RNA.

Severity Assessment of Japanese Cedar Pollinosis Using the Practical Guideline for the Management of Allergic Rhinitis in Japan and the Allergic Rhinitis and its Impact on Asthma Guideline

BACKGROUND This study intended to assess the severity of Japanese cedar pollinosis using the Practical Guideline for the Management of Allergic Rhinitis in Japan (PG-MARJ) and the Allergic Rhinitis and its Impact on Asthma (ARIA) Guideline. METHODS An Internet questionnaire survey of patients with pollinosis was conducted in mid-May 2011 and responses were obtained from 3382 individuals who had potential symptoms of Japanese cedar pollinosis from February to early May 2011 and who had experienced such symptoms for at least two pollen seasons. RESULTS According to PG-MARJ, 23.5% of the respondents had severest rhinitis, 29.4% severe rhinitis, 31.3% moderate rhinitis, 13.8% mild rhinitis and 2.0% asymptomatic rhinitis. According to ARIA, 67.2% of them had moderate/severe persistent rhinitis, 23.8% moderate/severe intermittent rhinitis, 4.4% mild persistent rhinitis and 4.6% mild intermittent rhinitis. CONCLUSIONS Moderate to severe rhinitis was diagnosed in more than 80% of the respondents according to PG-MARJ, while moderate/severe rhinitis was diagnosed in more than 90% of the respondents according to ARIA. Most of the respondents suffered relatively severe pollinosis. More than 80% of the respondents had all the three major symptoms (i.e., sneezing, rhinorrhea and nasal blockage). Disagreement in the severity assessment between the two guidelines was noted in approximately 20% of the respondents.

Squamous cell carcinoma of the nasolacrimal duct

Tumors originating from the nasolacrimal duct are exceedingly rare. Only a few cases have been reported previously. In advanced cases with extended tumor, differential diagnosis from lacrimal sac tumor is difficult. A 68-year-old Japanese man with intractable dacryocystitis was examined with intranasal endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). Squamous cell carcinoma extended from a medial site in the left orbit to the lacrimal orifice. En bloc resection was performed and histopathological examination of the surgical specimen using serial section suggested that the origin of the tumor was located in the nasolacrimal duct. This is the first case in nasolacrimal duct carcinoma whose differential diagnosis of origin has been studied in detail. We showed that pathological study using serial section along the duct provides useful information for diagnosing the tumor origin in addition to that obtained from imaging studies.