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Nontypeable Haemophilus influenzae (NTHi) strains form a major group of pathogenic bacteria that colonizes the nasopharynx and causes otitis media in young children. At present, there is no licensed vaccine for NTHi. Because NTHi colonizes the upper respiratory tract and forms biofilms that cause subsequent infectious events, a nasal vaccine that induces NTHi-specific secretory IgA capable of preventing biofilm formation in the respiratory tract is desirable. Here, we developed a cationic cholesteryl pullulan-based (cCHP nanogel) nasal vaccine containing the NTHi surface antigen P6 (cCHP-P6) as a universal vaccine antigen, because P6 expression is conserved among 90% of NTHi strains. Nasal immunization of mice with cCHP-P6 effectively induced P6-specific IgA in mucosal fluids, including nasal and middle ear washes. The vaccine-induced P6-specific IgA showed direct binding to the NTHi via the surface P6 proteins, resulting in the inhibition of NTHi biofilm formation. cCHP-P6 nasal vaccine thus protected mice from intranasal NTHi challenge by reducing NTHi colonization of nasal tissues and eventually eliminated the bacteria. In addition, the vaccine-induced IgA bound to different NTHi clinical isolates from patients with otitis media and inhibited NTHi attachment in a three-dimensional in vitro model of the human nasal epithelial surface. Therefore, the cCHP-P6 nanogel nasal vaccine induced effective protection in the airway mucosa, making it a strong vaccine candidate for preventing NTHi-induced infectious diseases, such as otitis media, sinusitis, and pneumonia.

Aim: The purpose of this report was to determine sudden death following operation, radiotherapy (RT), or chemoradiotherapy (CRT) for head and neck cancer. Material and methods: Data from 729 consecutive patients diagnosed with head and neck cancer (confirmed using multiple modalities) who underwent operation, RT, or CRT at Kagoshima University Hospital between April 2011, and March 2020 were analyzed. A total of 199 patients underwent operation, 223 patients underwent RT and 307 underwent CRT. A total of 175 patients who received operation, 118 patients who received RT, and 190 who received CRT showed a complete response. Results: There were 13 cases of sudden death reported in 10 years. 12 were male and 1 was female. Sudden death occurred in 3/175 patients (1.7%) who received operation, 4/118 (3.4%) who received RT, and 6/190 (3.1%) who received CRT. Conclusions: We present the first report on cases of sudden death after operation, RT, and CRT for head and neck cancer. Otolaryngologists should still follow these patients carefully after such a treatment given that sudden death does occur in some patients. [ABSTRACT FROM AUTHOR]

Background: Tonsillectomy combined with steroid pulse therapy was reported to be effective for patients with IgA nephropathy. However, the mechanisms of the effect of tonsillectomy on IgA nephropathy are unknown. Aim: The aim of this study was to investigate the involvement of the phosphorylcholine (PC)-specific immune response in the tonsils and peripheral blood of patients with IgA nephropathy. Material and methods: Tonsillar lymphocytes were isolated and the number of PC-specific immunoglobulin-producing cells was measured. Additionally, serum PC-specific immunoglobulin levels were quantified and compared with laboratory findings. Results: The number of PC-specific IgA-producing cells was increased in the tonsils of patients with IgA nephropathy. The value was significantly elevated in the group with a higher risk of initiating dialysis. In contrast, PC-specific IgM levels in the serum were significantly elevated in the group with a lower risk of initiating dialysis. Conclusions and significance: PC-specific immune responses in the tonsils and peripheral blood may be related to the pathological mechanism and progression of IgA nephropathy. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Intranasal immunization with phosphorylcholine (PC) is known to reduce immunoglobulin (Ig)E production. However, its effects on the occurrence of allergic rhinitis (AR) are unknown. This study was performed to evaluate the effects of PC-keyhole limpet hemocyanin (PC-KLH) and to examine the effects on the occurrence of AR in a murine model of AR.Study Design: In vivo study using an animal model.Methods: Forty-five female BALB/c mice were divided into three groups; those pretreated with intranasal administration of PC-KLH followed by intraperitoneal sensitization and nasal challenge with ovalbumin (OVA) (group A), those untreated with PC-KLH followed by sensitization and nasal challenge with OVA (group B), and those untreated with PC-KLH or OVA as controls (group C). Nasal symptoms, allergic inflammation in the nasal mucosa, OVA specific IgE production, and cytokine profile were compared among those three groups. Dendritic cells (DCs) were isolated from splenic cells and PC-KLH-stimulated interleukin (IL)-12p40 production was measured.Results: The mice pretreated with PC-KLH showed lower allergic nasal symptoms and inflammation compared to untreated mice. The levels of total IgE and OVA-specific IgE in serum, and IL-4 production by nasal and splenic CD4+ T cells were significantly reduced by PC-KLH pretreatment. Furthermore, IL-12p40 production by DCs was induced by PC-KLH in a dose-dependent manner.Conclusions: Intranasal administration of PC-KLH suppressed allergic inflammation in nasal mucosa and antigen-specific IgE production by downregulating Th2-type immune response. Intranasal immunization with PC might be useful to prevent AR and upper airway bacterial infection.Level Of Evidence: NA. Laryngoscope, 128:E234-E240, 2018. [ABSTRACT FROM AUTHOR]

Objective: Pneumococcal infection caused by Streptococcus pneumoniae is a major upper respiratory tract disease that causes severe illness and mortality. Therefore, it is important to develop safe and effective vaccines to prevent pneumococcal infections. The goal of the study was to investigate the effectiveness of transcutaneous immunization (TCI) for induction of pneumococcal surface protein A (PspA) responses in the upper respiratory tract.Methods: C57BL/6 mice were transcutaneously immunized with 1 μg of PspA and 2 μg of cholera toxin (CT) six times at weekly intervals and compared with transcutaneously treated controls (PBS alone/PspA alone/CT alone). Two weeks after the final immunization, nasal washes (NWs), saliva, and plasma samples were collected and subjected to a PspA-specific ELISA. Three weeks after the final immunization, mice were challenged with S. pneumoniae strain EF3030, and the numbers of CFUs in NWs and nasal passages (NPs) were determined.Results: Higher levels of PspA-specific IgM, IgG, and IgA Abs were noted in plasma of TCI with PspA plus CT compared with controls. Transcutaneous immunization mice also had significantly increased PspA-specific S-IgA Ab responses in NWs and saliva and, importantly, showed significantly lower numbers of bacteria CFUs in NWs and NPs compared with controls.Conclusion: These results show that TCI with PspA plus CT induces antigen-specific mucosal and systemic immune responses. This suggests that this method is an effective mucosal immunization strategy for induction of protective pneumococcal-specific Ab responses in blockade of S. pneumoniae colonization of the nasal cavity.Level Of Evidence: NA. Laryngoscope, 128:E91-E96, 2018. [ABSTRACT FROM AUTHOR]

Objective: One in 1000-3000 carriers of human T-cell leukemia virus type 1 (HTLV-1) develops adult T-cell leukemia/lymphoma (ATLL) per year; however, the pathogenic mechanism is not completely clear. We have observed that some patients with squamous cell carcinoma (SCC) develop ATLL during treatment at our hospital. The aim of this study was to examine treatment factors associated with onset of ATLL through an evaluation of the therapeutic background of these patients.Methods: The impact of radiotherapy, chemotherapy and surgery on occurrence of ATLL was evaluated in 146 patients with head and neck SCC who were treated at our hospital between April 2010 and December 2013.Results: Of 146 patients, 17 were HTLV-1 positive and 6 developed ATLL. There was a significant relationship between ATLL development and administration of S-1 chemotherapy (p=0.0003), but not with use of radiotherapy, surgery or other drugs.Conclusion: The involvement of S-1 chemotherapy in ATLL development suggests that a test for HTLV-1 antibody should be performed before treatment and that S-1 should not be administered in HTLV-1 positive patients with head and neck carcinoma. [ABSTRACT FROM AUTHOR]

Objective Transcutaneous immunization (TCI) is a novel route of vaccination through application of a topical vaccine antigen on the skin. Phosphorylcholine (PC) is a structural component of a variety of pathogens and anti-PC immune responses protect mice against invasive bacterial diseases. The purpose of the study was to examine the effect of TCI using PC in BALB/c mice. Methods TCI was performed in BALB/c mice using PC–keyhole limpet hemocyanin (KLH) plus cholera toxin (CT). Immunogenicity was evaluated by measuring PC-specific IgG and specific IgG1, IgG2a, IgM, IgA, and secretory IgA antibodies by ELISA. The concentrations of IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-γ were also measured using ELISA for mouse. Results Six months after immunization, IgG after TCI using PC plus CT was significantly higher than in controls, but this was not found for IgA. In saliva, secretory IgA antibodies decreased with a peak level at 2–3 months. IgG1 was significantly higher than IgG2 after TCI. Production of IL-4 from CD4 + cells was significantly higher after TCI than in controls, whereas production of IFN-γ, IL-5, IL-12 and IL-13 was not detected in either group. Conclusion These results suggest that TCI using PC plus CT with BALB/c mice is a simple approach for induction of systemic and mucosal immune responses that are shifted in the Th-2 direction. [ABSTRACT FROM AUTHOR]

Conclusion: Keratin-specific immune responses in tonsils may be associated with the pathogenesis of pustulosis palmaris et plantaris (PPP). Evaluation of keratin-specific immune responses in tonsils might be useful to predict the effectiveness of tonsillectomy for patients with PPP. Objectives: The aim of the present study was to clarify the role of keratin-specific immune responses in the pathogenesis of PPP in tonsils. It has been reported that anti-keratin antibodies in serum were higher in patients with PPP and decreased after tonsillectomy, indicating that anti-keratin antibodies might be generated in tonsils. Methods: In order to demonstrate the presence of keratin-specific immune responses in tonsils, the numbers of keratin-specific antibody-forming cells (AFCs) in tonsillar and peripheral blood lymphocytes were examined by enzyme-linked immunospot assay. The prognosis of PPP was compared after tonsillectomy. Results: The numbers of keratin-specific IgM and IgG AFCs in tonsils and of IgG AFCs in peripheral blood were significantly increased in patients with PPP. The numbers of keratin-specific IgG AFCs in peripheral blood correlated positively with tonsil and serum IgG antibodies specific to keratin. Our data show that a good prognosis in patients with PPP depended on the numbers of keratin-specific IgG and IgM AFCs in peripheral blood and the levels of keratin-specific IgG antibodies in serum being significantly decreased 6 months after tonsillectomy. [ABSTRACT FROM AUTHOR]

Abstract: Many countries throughout the world have experienced an increase in the prevalence of allergic rhinitis (AR), which has come to be a major cause of morbidity in developed countries. The pathology underlying AR is regarded as IgE-mediated type I allergy characterized by mucosal inflammation that occurs in response to allergen exposure. In Japan, AR caused by Japanese cedar pollen, the most common allergic disease, has become a salient public health challenge. Almost all primary care physicians and otorhinolaryngologists have been consulted by AR patients between February and April. Although most such patients have received treatment, numerous patients with AR have not received proper examinations for AR. Clinical guidelines are systematically developed statements that are designed to help practitioners make decisions about appropriate and effective health care. Guidelines in many countries including Japan have been published for AR. Unfortunately, those guidelines have remained untested. Moreover, they might be difficult for non-specialists to use. In this review, we specifically examine the present standard examination for diagnosis of AR and optimal classification for AR in Japan. We hope that this review would be used not only for the support of daily practice but also for selection of AR patients for clinical trials. [Copyright &y& Elsevier]

Abstract: Objective: In Japan, fourteen-membered ring macrolides, antibacterial agents, and S-carboxymethylcysteine (SCMC; carbocisteine), a mucolytic, are commonly used to treat chronic rhinosinusitis (CRS), and they are also used in combination. However, no large-scale randomized study has examined the effects of these pharmacotherapies. The aim of this study is to evaluate the effect of combined administration of clarithromycin (CAM), a fourteen-membered ring macrolide, and SCMC, compared with CAM single therapy. Methods: Patients with CRS were centrally registered and randomly assigned to treatment with CAM (200mg/day) alone (monotherapy group) or CAM (200mg/day) in combination with SCMC (1500mg/day; combination group) for 12 weeks. We assessed the clinical efficacy of the treatments using measures of subjective symptoms and objective findings, health-related quality of life (HRQOL) determined by the 20-Item Sino-Nasal Outcome Test (SNOT-20) score and computed tomography (CT) score. Results: Four hundred twenty-five subjects were enrolled (combination group, 213; monotherapy group, 212). At week 12 of treatment, the rate of effectiveness was significantly higher in the combination group (64.2%) compared with the monotherapy group (45.6%; P =0.001). In addition, objective findings, including characteristics of nasal discharge (P =0.008) and post-nasal discharge (P =0.002) were significantly improved in the combination group. In both groups, SNOT-20 and CT scores were significantly improved from week 0 (P <0.001), and were not significantly different between groups. Conclusion: The results indicated that long-term combination therapy with SCMC at a dose of 1500mg/day and CAM at a dose of 200mg/day is effective for improving subjective symptoms and objective findings in adult patients with CRS. [Copyright &y& Elsevier]

Objectives/Hypothesis: Viral upper respiratory tract infections (URIs) are often followed by secondary bacterial infections. To better understand this phenomenon, we examined the impact of the viral agent polyinosine-polycytidylic acid [Poly (I:C)] on the adherence of Streptococcus pneumoniae (Spn) to pharyngeal epithelial cells. Study Design: In vitro model of cultured human pharyngeal epithelial cells. Methods: Detroit 562 cells, a human pharyngeal carcinoma cell line, were pretreated with Poly (I:C). Poly (I:C)-induced expression of platelet-activating factor receptor (PAF-R) was assayed using real-time polymerase chain reaction, flow cytometry, and immunofluorescence microscopy. Bacterial adhesion to these epithelial cells was assessed using immunofluorescence microscopy and colony formation assays. Results: Pretreatment with Poly (I:C) increased mRNA and protein expression of PAF-R in Detroit 562 cells and enhanced the adherence of Spn to these epithelial cells. Conclusions: RNA viral infection can enhance PAF-R expression in epithelial cells and increase the adherence of Spn. These findings might explain in part the mechanisms that underlie the increase in bacterial infection following URIs. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective of this study was to assess the reliability and validity of a Japanese version of the 20-Item Sino-Nasal Outcome Test SNOT-20, which is one of the quality-of-life (QOL) evaluation sheets for chronic rhinosinusitis (CRS), and assess its reliability and validity. Methods: The SNOT-20 was conducted in patients with CRS and in healthy volunteers. The response rate was evaluated as the feasibility of this test, and reliability and internal consistency were assessed as reliability. In addition, concurrent validity and discriminant validity were assessed as validity. Results: Regarding the feasibility of this test, the response rate for each question item in the SNOT-20 was nearly 100% for all 20 items. For reliability, test–retest reliability was r =0.890 and the internal consistency was α =0.903. For validity, the concurrent validity was r =0.162 when compared with objective findings in the nasal cavity, and was r =0.431 when compared with the score for general physical condition, which evaluate the patient''s general condition. Discriminant validity was significantly higher in patients with CRS than in healthy volunteers (p <0.001). Moreover, when the discriminant validity was assessed using an ROC (receiver operating characteristic) curve, it was found that ROC-AUC (the area under the curve)=0.775. Conclusion: The reliability and validity of a Japanese version of the SNOT-20 were assessed in this study. It is thought that the SNOT-20 serves as a useful QOL evaluation sheet for CRS. [Copyright &y& Elsevier]

Objectives/Hypothesis: One of the major functions of vascular endothelial growth factor (VEGF) is increasing vascular permeability. We previously reported that VEGF is present in nasal secretions in rhinosinusitis, particularly in allergic rhinitis, and is hyperproduced immediately after antigen provocation. However, its function in nasal mucosa has not yet been investigated. This study was designed to estimate the increased vascular permeability by VEGF in nasal mucosa and to discuss its possible role in allergic rhinitis. Study Design: Prospective animal experiment. Methods: Hartley guinea pigs were used. Ethyl carbamate was injected into the abdomen for anesthesia, followed by intravenous injection of Evans blue into the femoral vein. Phosphate buffered saline, histamine, or VEGF was then applied to nasal cavities. Nasal mucosa was harvested after saline reflux from heart with phlebotomy by amputating the abdominal aorta. Tissue samples were soaked in formamide for 12 hours at 63°C to extract dye exudates from nasal mucosa. To analyze vascular permeability, dye was quantified by colorimetry. Results: VEGF increased vascular permeability in nasal mucosa, and was more than 1 × 106 times more potent than histamine on the basis of molar units. Although increased vascular permeability by VEGF was not inhibited by histamine 1 receptor antagonist, it was markedly inhibited by anti-VEGF receptor antibodies. Conclusions: VEGF increased vascular permeability to a greater degree than histamine in nasal mucosa via a different pathway. Regulating VEGF may be a new therapeutic option for persistent nasal symptoms in allergic rhinitis. Laryngoscope, 2010 [ABSTRACT FROM AUTHOR]

Conclusions. The effect of a zinc-containing compound, Polaprezinc, was shown to clinically improve the disease conditions of idiopathic taste disorders with no serious side effects in a well controlled double-blinded clinical study. Objectives. The purpose of the present study was to evaluate the efficacy and safety of a zinc-containing compound in the treatment of patients with idiopathic taste disorders, including patients with low serum zinc, by a Good Clinical Practice (GCP)-compliant, randomized, placebo-controlled, double-blind, multi-center clinical study. Subjects and methods. A group of 109 patients suffering from taste disorders was assigned into placebo and three treatment groups. Each group of patients was given either placebo (n=28), or 17 mg (n=27), 34 mg (n=26) or 68 mg (n=28) of oral zinc, Polaprezinc preparations, daily for 12 weeks. Results. The group of patients given 68 mg zinc showed a significant improvement in their gustatory sensitivity compared with the placebo group. The most common side effects observed were increase in serum triglyceride and serum alkaline phosphatase, decrease in serum iron, and some gastrointestinal incidents, although they were not serious. [ABSTRACT FROM AUTHOR]

Presents research on the development of vaccines for otitis media. Demonstration of the reduction of the nasopharyngeal carriage of vaccine-type pneumococci; Advantage of pneumococcal protein vaccines over PS-protein conjugate vaccines; Determination of the location of the Hap protein responsible for binding to eukaryotic cells and extracellular matrix protein.