Shinji Nishioka

Genomic structure of the human ING1 gene and tumor-specific mutations detected in head and neck squamous cell carcinomas

We characterized the genomic structure of the human ING1 gene, a candidate tumor suppressor gene, and found that the gene has three exons. We also demonstrated that four mRNA variants were transcribed from three different promoter regions. Of 34 informative cases of head and neck squamous cell carcinoma, 68% of tumors showed loss of heterozygosity at chromosome 13q33-34, where the ING1 gene is located. Here we present the first report that three missense mutations and three silent changes were detected in the ING1 gene in 6 of 23 tumors with allelic loss at the 13q33-34 region. These missense mutations were found within the PHD finger domain and nuclear localization motif in ING1 protein, probably abrogating the normal function.

Human papillomavirus as a risk factor for head and neck cancers--a case-control study.

A retrospective, case-control study was conducted to examine the relationship between the presence of human papillomavirus types 16 and 18 (HPV16/18) DNA and the risk of head and neck cancers. Twelve out of 74 (16.2%) head and neck cancers contained HPV16/18 DNA, while 3 out of 70 (4.2%) non-cancer controls showed HPV16/18 positivity by polymerase chain reaction. The presence of HPV16/18 DNA was associated with an increased risk of head and neck cancer formation, showing an odds ratio of 4.32, with a 95% confidence interval of 1.26-14.78. Although its epidemiological impact might be smaller than that of other factors like cigarette smoking, the presence of HPV16/18 DNA in the aerodigestive tract is suggested to be a risk factor for human head and neck cancers.

Presence and characterization of sensitization to staphylococcal enterotoxins in patients with allergic rhinitis.

Exotoxins derived from Staphylococcus aureus appear to be involved in the pathogenesis of allergic diseases, especially atopic dermatitis (AD). However, little is known about sensitization to enterotoxins in cases of respiratory allergies. Because the nasal cavity is a primary site of colonization by S. aureus, we sought to determine the prevalence and role of serum immunoglobulin E (IgE) antibodies against staphylococcal enterotoxin A (SEA) and SEB in patients with allergic rhinitis (AR). The presence of SEA- and SEB-specific IgE was determined in 40 patients with AR and 16 healthy control subjects. In the rhinitis group, nasal symptom score, total serum IgE, sensitization to other inhaled allergens and the presence of sinusitis were determined. Twenty-five percent of patients with AR were sensitized to SEA/SEB whereas 6.3% of controls were sensitized to the toxins. Sensitization to SEB was predominant relative to SEA. There were no significant differences in the severity of nasal symptoms and complications of other allergic diseases including AD and bronchial asthma, between patients with or without sensitization to SEA/SEB. However, patients sensitized to these toxins were likely to show increased total serum IgE and polyvalent sensitization, suggesting that exposure and subsequent sensitization to SEA/SEB may be involved in polyvalent sensitization.

Role of Macrophage Migration Inhibitory Factor in Otitis Media with Effusion in Adults

ABSTRACT Otitis media with effusion (OME) is one of the most common ear diseases. Bacterial endotoxins and several inflammatory cytokines appear to be involved in the pathogenesis of OME in children; however, little is known of the immunological aspects of the onset of OME in adults. We sought to determine the presence of macrophage migration inhibitory factor (MIF) as well as interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α), RANTES (regulated upon activation, normal T-cell expressed and presumably secreted), and endotoxin in middle ear effusions (MEEs) from adult patients with OME. In addition, the levels of MIF in MEEs from adults and children were compared. MEE was obtained from 95 adults and 11 children. The levels of MIF, IL-1β, TNF-α, and RANTES were determined by enzyme-linked immunosorbent assay, and the concentrations of endotoxin and total protein were determined by the Endospec assay and bicinchoninic acid assay, respectively. MIF was detected in 97.9% of the MEEs from adults, while endotoxin, IL-1β, TNF-α, and RANTES were detected in 96.8, 12.6, 5.3, and 43.9%, respectively. In addition, the level of MIF was significantly higher than those of endotoxin, IL-1β, and TNF-α. A positive correlation between the levels of MIF and endotoxin was observed. MIF and endotoxin were detected in 81.8 and 72.7%, respectively, of the MEEs from the children. The level of MIF was significantly higher in the children, and conversely that of endotoxin was significantly higher in the adults. These results suggest that the interaction between MIF and endotoxin may promote fluid collection in the middle ear, particularly in adults.

Comparison of Tumor Markers in Patients with Squamous Cell Carcinoma of the Head and Neck

The serum concentrations of three separate tumor markers, squamous cell carcinoma antigen (SCC Ag), carcinoembryonic antigen (CEA) and Cyfra 21-1 were clinically correlated in 86 randomly selected patients with squamous cell carcinoma involving the head and neck. Positive findings for each tumor marker were totalled and statistically analysed. The upper limits of normal for SCC Ag, CEA and Cyfra 21-1 were set at 1.5, 2.5 and 2.0 ng/ml, respectively. Positivity rates were 20.6% for SCC Ag, 14.0% for CEA and 41.7% for Cyfra 21-1. Elevated Cyfra 21-1 concentrations correlated somewhat with age, whereas elevated CEA levels correlated with the site of tumor involvement. Overall, Cyfra 21-1 appeared to be the most useful marker in head and neck squamous cell carcinoma.