Tadahito Saito

Specific mucosal immunity and enhanced nasopharyngeal clearance of nontypeable Haemophilus influenzae after intranasal immunization with outer membrane protein P6 and cholera toxin

Nontypeable Haemophilus influenzae (NTHi) is one of the leading pathogens in otitis media. Studies of vaccines against NTHi have focused on outer membrane proteins (OMPs). One outer membrane protein P6 is highly conserved among strains and is an attractive candidate for a subunit bacterial vaccine. In this study, mucosal immunity induced by intranasal immunization with P6 and cholera toxin (CT) was investigated in a mouse model. Intranasal immunization with P6 and CT evoked a good mucosal IgA as well as a systemic IgG response against P6. On the other hand, intranasal immunization with P6 alone induced a weak mucosal IgA response. Enzyme linked immunospot assay detected anti-P6 specific antibody producing cells in the nasopharyngeal mucosa of immunized mice. The protective response of intranasal immunization was demonstrated by enhancement of nasopharyngeal clearance of NTHi and inhibition of adherence of NTHi to cultured human epithelial cells. Based on these results, intranasal immunization with P6 and CT may be an effective approach to protect human from H. influenzae infections in the upper respiratory tract.

Nasopharyngeal Carriage of Drug-resistant Streptococcus pneumoniae in Children with Acute Otitis Media Evaluated by Polymerase Chain Reaction-based Genotyping of Penicillin-binding Proteins

A polymerase chain reaction (PCR)-based genotyping of the penicillin-binding protein (PBP) genes pbp1a , pbp2x and pbp2b was used to characterize Streptococcus pneumoniae isolated from the nasopharynx of children with acute otitis media (AOM). Mutations were observed in pbp1a , pbp2x and pbp2b genes in 36.5% of the strains. Decreased susceptibility to g -lactam antibiotics was closely associated with the frequency of mutations in the three PBP genes. Of penicillin-intermediately-resistant S. pneumoniae strains, 54.5% appeared to be genetically similar to penicillin-resistant S. pneumoniae strains. Of penicillin-susceptible S. pneumoniae strains, 33.3% had mutations in the pbp2x gene and showed relatively high MICs to cephalosporins. Strains with mutations in the three PBP genes were often isolated from children h 2 years old. Evaluation of mutations in PBP genes using PCR will prove useful for studying the epidemiology of antibiotic resistance.

Analysis of Viral Infection in Patients with IgA Nephropathy

We investigated viral infections in the tonsils, pharynx and renal tissues of patients with IgA nephropathy using cell culture, polymerase chain reaction (PCR) and immuno-fluorescent techniques, and measured antibody titers against numerous types of viruses. Neutralization tests found no significant inhibition of growth of adenovirus-1, 2, 3, 4, 5, 6, 7, 11 or 19, Coxsackie virus-A7, A9, A16, B1, B2, B3, B4, B5 or B6, or RS virus. Swabs of the oral cavity of patients with IgA nephropathy were cultured with Hel cells, MDCK cells, FL cells, BHK-21 cells and RD-18S cells. No cytopathic effect was detected in any of these cell cultures. We failed to detect the presence of herpes simplex virus-1 and -2, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus (EBV)-1 and -2 in tonsils, renal tissues and mouthwashings from patients with IgA nephropathy. On the other hand, EBV alone was detected with the PCR technique, in mouthwashings from 6 out of 14 patients with IgA nephropathy (42%). Immunohistological and serological analyses were done to examine the relationship between EBV and IgA nephropathy. No evidence was obtained that EBV-infected B lymphocytes were producing IgA. It seems unlikely that the viral infections examined in this study play a significant role in the pathogenesis of IgA nephropathy.

Local Administration Trials of Interleukin-2 for Head and Neck Cancer

Recombinant interleukin-2 (rIL-2) has been administered locally in 20 patients with head and neck cancer. Two complete responses in lower lip cancer and 1 partial response in lingual cancer have been obtained. Immunohistological study reveals that tumor infiltrating lymphocytes (TILs), including activated T lymphocytes and natural killer cells, are increased after rIL-2 use. Intraarterial chemotherapy, performed subsequently to the local use of rIL-2 results in a dramatic decrease in tumor size within a short time, and a high frequency of CR cases is observed. Local use of rIL-2 is beneficial for treatment of head and neck cancers, and induction immunochemotherapy combining locally used rIL-2 and arterially infused anticancer drugs plays an important role in a multidisciplinary treatment for these cancers.

Middle ear adenoma with neuroendocrine differentiation

The lining of the middle ear cleft is normally a thin modified respiratory type mucosa. Normal mucosa of the middle ear is devoid of salivary type seromucous glands. Middle ear adenoma is a rare tumor that seems to be derived from the middle ear mucosa. This tumor has been previously described under a variety of names because of its different nature and biological behavior. We herein report a case of middle ear tumor that shows adenomatous and neuroendocrine features. A 64-year-old woman presented with a history of hearing loss, tinnitus and stuffy feeling of the right ear. The patient was treated two times for ear polyp. She finally underwent a tympanomastoidectomy and there was no evidence of recurrence 18 months after the procedure. Histopathological examination displayed cuboidal and columnar cells, arranged as glands, trabeculae and solid sheets. Neuroendocrine differentiation was revealed by immunohistochemical staining with polyclonal antibodies against neuron specific enolase and chromogranin antigens.

Mucoepidermoid Carcinoma in the Nasopharynx.

We report a case of mucoepidermoid carcinoma in the nasopharynx. A woman, aged 59, who suffered from chronic otitis media with effusion was referred to our department due to a mass lesion on the Rosenmullers fossa. The mass lesion was pathologically diagnosed as a mucoepidermoid carcinoma. CT and MRI scans showed a well bordered round shadow which was limited to the orifice of the left eustachian tube, without invasion of the skull base.As the patient did not agree to surgical treatment, we selected radiotherapy using a gamma knife for treatment of the nasopharyngeal tumor. The tumor responded well to gamma knife treatment and disappeared with 30Gy irradiation (Edge dose). The patient has shown no recurrence of the tumor for a year and 6 months after treatment. Gamma knife radiotherapy may be one potential treatment strategy for intractable lesions of the head and neck such as mucoepidermoid carcinoma in the nasopharynx.

A Report of Meningioma Extending to the Middle Ear.

Intracranial meningioma is common, 13 to 18% of all intracranial tumors.However, extracranial meningioma, in paticular middle ear meningioma is very rare. Two of our patients had meningiomas extending to middle ear cavity, a 49-year-old and 59-year-old females. In both cases, it was considered that the tumor had extended to the middle ear cavity through the jugular foramen. This route of extension of tumors causes hoarseness due to invasion of the vagus nerve. In the diagnosis of hoarseness, such intracranial lesions must be kept in mind.

Syphilis of the inner ear causing fluctuating hearing loss responsive to steroid therapy.

Inner ear syphilis is a well-known disorder, associated with various chronic symptoms, which is difficult to treat. The present report describes late congenital inner ear syphilis in a patient followed for about two years. Fluctuating hearing loss responded to long-term steroid therapy. The general treatment of inner ear syphilis is discussed with reference to the previous literature.

Significance of Immunotherapy in Head and Neck Cancer

Immunological surveillance has been elucidated and many cytokines, which participate in the immunological response between cancer and host, has been detected with recent progress of biotechnology. Furthermore, recent genetic engineering enables clinical application of these cytokines in cancer treatment. In this article, the role of immunotherapy in multimodal treatment for head and neck cancer is reviewed, and clinical evaluation and prospect of local administration of recombinant interleukin-2 (rIL-2) is discussed.

MRI in head and neck.

Magnetic resonance imaging (MRI) was used in the diagnosis of head and neck tumors. The advantages and the problems of MRI are discussed and compared with those of X-ray computed tomography.MRI provides more detailed information about the nature and the depth of in-filtration of tumors, not only because of the excellent soft-tissue contrast, but also because multiple directions can be used. An additional benefit is the much easier identification of cervical vascular structures by MRI.