Csk restrains BCR-mediated ROS production and contributes to germinal center selection and affinity maturation.

Compared with naïve B cells, the B cell receptor (BCR) signal in germinal center (GC) B cells is attenuated; however, the significance of this signaling attenuation has not been well defined. Here, to investigate the role of attenuation of BCR signaling, we employed a Csk mutant mouse model in which Csk deficiency in GC B cells resulted in augmentation of net BCR signaling with no apparent effect on antigen presentation. We found that Csk is required for GC maintenance and efficient antibody affinity maturation. Mechanistically, ROS-induced apoptosis was exacerbated concomitantly with mitochondrial dysfunction in Csk-deficient GC B cells. Hence, our data suggest that attenuation of the BCR signal restrains hyper-ROS production, thereby protecting GC B cells from apoptosis and contributing to efficient affinity maturation.

Hydrophobic Components in Light-Yellow Pulp Sweet Potato (Ipomoea batatas (L.) Lam.) Tubers Suppress LPS-Induced Inflammatory Responses in RAW264.7 Cells via Activation of the Nrf2 Pathway.

Sweet potato is a crop that is widely consumed all over the world and is thought to contribute to health maintenance due to its abundant nutrients and phytochemicals. Previous studies on the functionality of sweet potatoes have focused on varieties that have colored pulp, such as purple and orange, which contain high levels of specific phytochemicals. Therefore, in the present study, we evaluated the anti-inflammatory effects of light-yellow-fleshed sweet potatoes, which have received little attention. After freeze-drying sweet potatoes harvested in 2020, extracts were prepared from the leaves, stems, roots, and tubers in 100% ethanol. Mouse macrophage-like cell line RAW264.7 cells were cultured with 10 µg/mL of the extracts and induced lipopolysaccharide (LPS)-stimulated inflammation. Of the extracts, the tuber extracts showed the highest suppression of LPS-induced interleukin-6 (IL-6) gene expression and production in RAW264.7, which was attributed to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) oxidative stress response pathway. In addition, preparative high-performance liquid chromatography (HPLC) experiments suggested that hydrophobic components specific to the tuber were the main body of activity. In previous studies, it has been shown that the tubers and leaves of sweet potatoes with colored pulp exhibit anti-inflammatory effects due to their rich phytochemicals, and our results show that the tubers with light-yellow pulp also exhibit the effects. Furthermore, we were able to show a part of the mechanism, which may contribute to the fundamental understanding of the treatment and prevention of inflammation by food-derived components.

Effects of Additional Granola in Children's Breakfast on Nutritional Balance, Sleep and Defecation: An Open-Label Randomized Cross-Over Trial.

The contribution of breakfast to daily nutrient intake is low, particularly among children, at only about 20%, and it is difficult to determine whether children are receiving adequate nutrients at breakfast. Although alterations in breakfast content are considered to affect lifestyle habits such as sleep and defecation, there have been few intervention studies in children. The relationship between nutritional balance, dietary intake, and lifestyle habits in children remains unclear. We conducted an intervention study on elementary school children's breakfasts and observed the effects of improving the nutritional balance of breakfast on sleep parameters and defecation status. An intervention study was conducted with 26 elementary school students in Tokyo. The study design was an open-label randomized cross-over trial. Subjects consumed their usual breakfast during the control period and a granola snack containing soy protein in addition to their usual breakfast during the intervention period. Questionnaires regarding breakfast, sleep, and bowel movements were administered during each period. Based on the answers to these questionnaires, we compared the nutritional sufficiency of macronutrients, vitamins, and minerals (29 in total), as well as changes in sleep parameters and defecation status. The additional consumption of granola snacks increased the breakfast intake of 15 nutrients. The changes were particularly significant for iron, vitamin B1, vitamin D, and dietary fiber. During the intervention, sleep duration was decreased and wake-up time became earlier. In terms of defecation, the intervention did not change stool characteristics, but the frequency of defecations per week increased on average by 1.2 per week. These results suggest that the nutritional balance and the amount of breakfast are linked to sleep and defecation and that improving breakfast content can lead to lifestyle improvements in children.

Pollen Allergy Screening with Allergen-Specific and Total Immunoglobulin E Titers.

Background: Allergic rhinitis is a typical type I hypersensitivity reaction, commonly caused by inhalant allergens. Accurate identification of the causative antigen is important for rapid diagnosis and treatment initiation. Objective: This study examined the efficiency of serum-based allergen-specific immunoglobulin E and total immunoglobulin E antibody titers in screening for pollen allergy. We also examined the effect of cross-reactive carbohydrate determinants on specific immunoglobulin E titers in screening for pollen allergy, one of the causes of false positivity in specific immunoglobulin E measurements. Methods: A questionnaire was used to evaluate the symptoms of pollinosis among participants who underwent a medical examination. One hundred and thirty-two participants reported pollen allergy symptoms and 127 reported an absence of symptoms. Specific immunoglobulin E levels were measured using the AlaSTAT 3g Allergy method. Seventeen components, including four types of cross-reactive carbohydrate determinant-specific immunoglobulin E antibodies, were measured and evaluated comparatively. Results: The sensitivity and specificity of the tests in predicting the presence or absence of pollen allergy were analyzed. The values of the areas under the curves for immunoglobulin E antibody levels against cedar, cypress, orchard grass, and ragweed pollen were 0.87, 0.82, 0.63, and 0.56, respectively. A cross-reactive carbohydrate determinant-related false-positive effect on the pollen specific immunoglobulin E titer was noted in pollen screening. Conclusion: Cedar pollen-specific immunoglobulin E titers showed sufficient accuracy for use in pollen allergy screening. The study of cross-reactive carbohydrate determinants suggested that subjects who tested positive for pollen often had false-positive results due to the impact of cross-reactive carbohydrate determinants.

Involvement of galanin and galanin receptor 2 in a mouse model of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is caused by allergic reaction to allergens such as pollen. Galanin (GAL), a neuropeptide that regulates inflammatory processes, is widely expressed in the central and peripheral nervous systems. Although neuropeptides are implicated in arthritis and chemically induced ileitis, their roles in AR remain unclear. METHODS: We developed a murine model of AR and generated control, systemic sensitization, mild AR, and severe AR groups. We examined GAL and GAL receptor (GALR) mRNA and protein levels and localization patterns in each group using reverse transcription PCR, western blotting, and immunohistochemical analyses. Additionally, we evaluated the effects of M871, a GALR2 antagonist, on mice with severe AR. RESULTS: Gal and Galr2 are expressed in nasal mucosa and brain (control) samples from control and AR mice. GAL and GALR2 were expressed at similar levels and localized to ciliated epithelial and submucosal gland cells of the nasal mucosa in all four groups. Intranasal M871 administration significantly reduced the incidence of nose rubbing behaviors and sneezing (p < 0.001 in 30 min, respectively) in severe AR mice relative to that in controls. Mechanistically, we postulate that GALR2 is expressed in B cells, and M871 administration reduces IgE production, as well as the number of B cells in tissues. CONCLUSIONS: GAL signaling may not change progressively with increasing nasal sensitization, suggesting that this signaling process exacerbates, rather than directly trigger, AR. GAL-GALR2 signaling likely mediates AR development, suggesting that its inhibition represents a novel therapeutic strategy for AR.

3D Body Parts Tracking of Mouse Based on RGB-D Video from Under an Open Field.

The mouse is a valuable animal model to address the neural mechanism of higher brain function and test the pharmacodynamics of new drugs. The development of novel behavioral analysis to detect subtleties of emotion is valuable for the evolution of neuroscience research and drug discovery. 3D pose estimation is expected to contribute significantly to them. Several methods for 3D pose estimation of the mouse using optical motion capture with markers and multiple cameras have been proposed, but these methods have problems such as preparing marker sets and the influence of the markers on mouse behavior. A low-cost and simple method for markerless 3D pose estimation of the mouse using a single RGB-D (Depth) camera is proposed. As a result, the proposed method improved the accuracy of limbs tracking compared to existing limbs tracking methods. In addition, this method could track other body parts (nose, base of tail) and the center of gravity.Clinical Relevance-This study could contribute to the development of neuroscience research and drug discovery by clarifying the relationship between subtle changes in mouse behavior and emotional movements.

The Prevalence of Odontogenic Pathology in Patients With Bilateral Rhinosinusitis.

OBJECTIVE: We investigated cases with opacification on maxillary sinus computed tomography (CT) among patients with rhinosinusitis with opacification in both paranasal sinuses (bilateral rhinosinusitis) to confirm the involvement of odontogenic infections. METHODS: This study included 75 patients who were diagnosed with bilateral rhinosinusitis based on clinical examination and evident opacification on at least one side on maxillary sinus imaging with computed tomography CT. The definition of odontogenic sinusitis was determined by examining EPT and oral findings, in addition to the CT and orthopantomography (OP), by one oral surgeon and two otolaryngologists. RESULTS: We found that 45.3% of patients had odontogenic infections, which were associated with multiple infected teeth in some cases. Odontogenic infection was observed in both sinuses in some patients. Sinusitis with polyps was frequently associated with dental infection, and some cases were also associated with mycosis. Almost no oral symptoms were observed. CONCLUSIONS: The results suggest that clinicians should consider odontogenic infection in patients with bilateral rhinosinusitis with opacification, on at least one side on maxillary sinus imaging. This means that accurate diagnosis may be challenging for otolaryngologist or dentists alone, suggesting that a collaboration between the two would be suitable for this task.

Odontogenic infection and antiresorptive agent-related osteonecrosis of the jaw with facial subcutaneous abscess formation: A retrospective clinical study of difficult-to-diagnose cases.

OBJECTIVE: The objective of this study was to analyze difficult-to-diagnose cases of odontogenic infection and antiresorptive agent-related osteonecrosis of the jaw (ARONJ) with facial subcutaneous abscesses by otolaryngologists. METHODS: The study was conducted in the department of otolaryngology of a university hospital. Seven patients exhibiting odontogenic infection and ARONJ with facial subcutaneous abscesses diagnosed at the department of otolaryngology in our hospital from January 2008 to December 2018 were included in the study. We investigated the following information obtained from the patients: clinical department for initial treatment, sex, age, offending tooth, causative disease, site of the fistula, symptoms, methods of diagnoses, and therapy. RESULTS: Odontogenic infection with facial subcutaneous abscess formation can occur in individuals in a wide range of age groups; however, the pathological manifestations of ARONJ are often observed in older women, frequently at the chin and accompanied by nodules and pain in the adjacent teeth. Computed tomography and orthopantomography are useful for diagnosis and are especially indicated for patients under long-term follow-up or with frequent recurrences. Magnetic resonance imaging, cytodiagnosis, and histological analysis might be necessary to exclude the possibility of tumors. Management of such facial subcutaneous abscesses comprises dental treatment and infection control, and f surgical removal of the abscess is usually not required. Treatments such as sequestrectomy and sitafloxacin administration are useful for patients with ARONJ. CONCLUSION: Our results demonstrated that for patients with facial subcutaneous abscesses, involvement of odontogenic infection and ARONJ should be considered.

Abducens Nerve Paralysis Induced by a Primary Solitary Sphenoid Sinus Mucocele with Broad Osseous Thinning at the Cranial Base.

Primary solitary sphenoid sinus mucocele is rare, generally presenting with headaches or eye symptoms at the anatomical site. We report the case of a 39-year-old woman incidentally diagnosed with sphenoid sinus mucocele during a complete medical checkup. Imaging revealed that the cystic wall had developed from the rear sphenoid sinus and had spread expansively to diminish the clivus; however, no symptoms were reported, and the patient was managed with close observation. During the follow-up period, diplopia developed suddenly due to isolated left-sided abducens nerve paralysis. An endoscopic endonasal approach was used to open the frontal cystic wall, and fascia lata and fat were used for cranial base reinforcement to avoid future cerebrospinal fluid leakage, resulting in improvement during the early stages of follow-up. Treatment options for sphenoid sinus mucoceles include close observation or surgery. In our case, we chose surgery because of an acute symptomatic manifestation during observation.

Relationships of opacification in the nasal sinuses, rhinosinusitis, and antiresorptive agent-related osteonecrosis of the jaw.

OBJECTIVE: Bone turnover suppression agents are widely used for prophylaxis of bone metastases from cancer and osteoporosis; the occurrence of their side effect, antiresorptive agent-related osteonecrosis of the jaw (ARONJ), has been increasing. We investigated the relationships between opacification in the nasal sinuses, rhinosinusitis, and ARONJ based on data obtained from oral surgeons. METHODS: We examined 132 patients who had been clinically diagnosed with ARONJ based on clinical observations; all patients had undergone treatment at the Departments of Otorhinolaryngology and Oral Surgery. In 16 of the 132 patients, we confirmed a diagnosis of osteonecrosis of the upper jaw and the presence of ipsilateral opacification of the maxillary sinus. We analyzed the data of these 16 patients in detail. RESULTS: Five of the 16 patients had some nasal symptoms and had been diagnosed with rhinosinusitis. The opacification of the rhinosinuses improved, partially improved, and remained unchanged after treatment in 10, three, and two patients, respectively; notably, imaging assessment could not be conducted after treatment in one case. CONCLUSIONS: Although there is no consensus regarding the treatment of sinusitis accompanying ARONJ, attempts to improve the causal foci and conservative treatment may offer favorable results; thorough investigation is necessary in refractory cases before determining the use of surgery.

Modified Lothrop (Draf III) procedure for the treatment of a recurrent orbitofrontal cholesterol granuloma: A case report.

Orbitofrontal cholesterol granuloma is a rare occurrence. Here, we present a case involving a 64-year-old man with a recurrent orbitofrontal cholesterol granuloma treated by the Modified Lothrop (Draf III) procedure. The patient, who had a history of trauma and previous sinus surgery, presented with chief complaints of nasal congestion, olfactory impairment, and diplopia. We suspected chronic sinusitis; computed tomography showed a soft-tissue shadow extending from the bilateral frontal sinuses to the ethmoid sinuses, with a cyst in the right orbitofrontal region. We performed endoscopic surgery for removal of the mass, and histopathological analysis of the resected specimen confirmed a diagnosis of cholesterol granuloma. The lesion recurred 2 months later, and we performed revision surgery using the Modified Lothrop or Draf III procedure. The patient showed no relapse at the 5-year follow-up. These findings suggest that the Draf III procedure is an effective surgical treatment for cholesterol granulomas.

Two Cases of Allergic Fungal Sinusitis with Differing Postoperative Course.

Allergic fungal sinusitis (AFS) often develops in unilateral paranasal sinuses, which must be differentiated from tumors. When AFS develops on both sides, however, it must be differentiated from eosinophilic chronic sinusitis with evident eosinophilic infiltration at nasal/paranasal sinus mucosa; both conditions are highly recurrent and commonly considered intractable paranasal sinusitis. Surgical correction is the primary treatment method for AFS, as it is essential to connect the paranasal sinus communication to ensure exhaustive resection of the pathologic mucosa and for nasal steroids to reach each paranasal sinus. We recently encountered two AFS cases with differing postoperative courses. Case 1 showed evident exacerbation in the computed tomography findings, which suggests progression to eosinophilic sinusitis. Case 2 showed a benign prognosis without recurrence. Close long-term follow-up should be mandatory after surgery for the treatment of AFS.

Biphasic low-grade nasopharyngeal papillary adenocarcinoma: a case report and literature review.

BACKGROUND: Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is distinctly rare. We report a patient with a uniquely biphasic LGNPPA; additionally, we review similar tumors reported in the literature. CASE PRESENTATION: A 56-year-old man presented with an asymptomatic pedunculated tumor in the vault of the nasopharynx, at the junction of the nasal septum and the roof, which was discovered during screening for laryngeal cancer. To obtain a definitive diagnosis, the patient underwent endoscopic endonasal surgery under general anesthesia. Immunohistochemical analysis of the tumor revealed it to be an LGNPPA with a prominent spindle cell component. CONCLUSION: To our knowledge, this is the fourth reported LGNPPA exhibiting a spindle cell component and the second with a prominent pathological condition. The prognosis of LGNPPA is usually excellent. Therefore, it is important for clinicians to scrutinize the lesion's pathology to avoid unnecessary, disfiguring surgery.

Gastrin-Releasing Peptide Is Involved in the Establishment of Allergic Rhinitis in Mice.

OBJECTIVE: Gastrin-releasing peptide (GRP) is a neuropeptide that targets transmembrane-type receptors. Its role in allergic rhinitis (AR) has yet to be investigated. The present study utilized the nasal mucosa of AR model mice to examine GRP and GRP receptor (GRPR) expression levels, localization, and other factors to evaluate their role in AR pathology. STUDY DESIGN: In vivo study in an animal model. METHODS: GRP and GRPR expression levels were examined in three different AR models established in BALB/c mice. In addition, a GRPR antagonist (RC-3095) was administered to AR mice to investigate its effect. The distribution of GRPR expression on mast cells in the nasal mucosa with AR was examined. Finally, we investigated the inhibitory effect of RC-3095 on allergy symptoms induced by histamine. RESULTS: GRP and GRPR were highly expressed in the nasal mucosal epithelium and interstitial tissues surrounding the nasal glands in AR groups according to immunostaining. GRP and GRPR expression as determined by western blotting increased in the nasal mucosa as the degree of nasal sensitization increased. In addition, the average counts of sneezing and nasal rubbing after treatment in the AR + RC-3095 group were significantly lower than those in the AR + nasal saline group. Mast cells often colocalized with GRPR around nasal glands. Moreover, RC-3095 was effective in reducing sneezing induced by histamine. CONCLUSION: The GRP-GRPR system is likely to be involved in allergic inflammation. This system may represent a novel therapeutic target for refractory AR. LEVEL OF EVIDENCE: NA. Laryngoscope, E377-E384, 2018.

Involvement of cross-reactive carbohydrate determinants-specific IgE in pollen allergy testing.

BACKGROUND: Specific IgE antibodies against the low-molecular-weight carbohydrate antigen that does not bridge IgE molecules on mast cells are not associated with clinical symptoms. Cross reactivity can be determined in allergen-specific IgE detection assays when the carbohydrate structures between pollen allergens and plant derived food allergens are similar; in such cases, false positive results for grain or legume allergens can be reported for pollen allergic patients who are not sensitized to those allergens. This phenomenon arises owing to the presence of cross-reactive carbohydrate determinants (CCDs). OBJECTIVE: This study aimed to assess the impact of CCD interference on the results for pollen allergen-specific IgE antibodies in the general adult population and to perform CCD inhibition tests evaluating the involvement of CCD on samples positive to pollen allergens. METHODS: Serum samples from 322 subjects were tested for IgE antibodies to pollens and CCD. The research subjects were given questionnaires about pollen allergic symptoms to help assess the presence of allergies. Allergen IgE antibodies for Japanese cedar, Japanese cypress, orchard grass, ragweed, MUXF, bromelain, horseradish peroxidase (HRP), and ascorbate oxidase (ASOD) were analyzed. RESULTS: It was observed that among individuals who tested positive to any of the pollen allergens, the positive ratio of CCD-specific IgE antibody was the highest for HRP (13.5%-50.0%). The results from the inhibition tests revealed that CCD was marginally present. Although IgE antibodies for cedar pollen did not react with CCD, IgE antibodies for Japanese cypress, orchard grass, and ragweed might be detected by the presence of CCD. CONCLUSION: The results of the inhibition tests revealed the obvious presence of CCD suggesting its involvement. Considering these findings, careful evaluation of patient IgE results should be performed for Japanese cypress, orchard grass, and ragweed.

Inhibition of epithelial-mesenchymal transition by cetuximab via the EGFR-GEP100-Arf6-AMAP1 pathway in head and neck cancer.

BACKGROUND: Despite improved survival by the addition of a monoclonal antibody against epidermal growth factor receptor (EGFR), cetuximab, to chemotherapy or radiotherapy for squamous cell carcinoma of the head and neck (SCCHN), cetuximab by itself is not a potent antiproliferative agent against SCCHN. We aimed to elucidate working mechanism of cetuximab in SCCHN. METHODS: The effect of cetuximab on the proliferation, migration, invasion, epithelial-mesenchymal transition, and signaling events downstream of the EGFR were investigated in 4 SCCHN cell lines. The in vivo efficacy of cetuximab was evaluated in a xenotransplant model. RESULTS: Cetuximab inhibited migration, invasion, epithelial-mesenchymal transition, and lymph node metastasis by suppressing EGFR-GEP100-Arf6-AMAP1 pathway, but it did not inhibit cancer cell proliferation. CONCLUSION: The improved survival by the addition of cetuximab is likely to be attributable to the antiepithelial-mesenchymal transition action of cetuximab via inhibiting EGFR-GEP100-Arf6-AMAP1 pathway. © 2016 Wiley Periodicals, Inc. Head Neck 39: 476-485, 2017.

Rhinogenic intracranial complication with postoperative frontal sinus pyocele and inverted papilloma in the nasal cavity: A case report and literature review.

We report a patient who had rhinogenic intracranial complication with postoperative frontal sinus pyocele and inverted papilloma in the nasal cavity. A 72-year-old woman had undergone surgery for frontal sinusitis via external incision at another hospital 13 years previously. Left-sided hemiparesis appeared in the patient and gradually worsened. Five days later, she exhibited disorientation, abnormal behavior, poor articulation, and difficulty in standing. Therefore, she was taken to the neurosurgery department by ambulance. An extensive frontal sinus pyocele was suspected, and a cerebral abscess and edema of the frontal lobe were observed on magnetic resonance imaging. After antibiotics, steroid and glycerol were administered for a few weeks; disorientation and left hemiparesis improved. Next, craniotomy for complete removal of the brain abscess by neurosurgeons and endoscopic endonasal surgery by otolaryngologists were carried out at the same surgery. From the analysis of the pathological mucosa sample taken from the right ethomoidal sinus during surgery, an inverted papilloma was diagnosed. The patient completely recovered and is currently receiving follow-up examination. Regarding rhinogenic intracranial complications, ascertaining clinical condition in order to determine the need for either immediate radical surgery, or for curative surgery after waiting for improvement of the overall body condition by conservative management, is still needed.

An Inflammatory Pseudotumor Arising from Pterygopalatine Fossa with Invasion to the Maxillary Sinus and Orbital Cavity.

We report a patient who had an inflammatory pseudotumor (IPT) that invaded to the maxillary sinus and orbital cavity, with the left pterygopalatine fossa as the principal site; this is a very rare case. The patient was an 83-year-old woman who suddenly became aware of impairment in the eyesight and visual field of the left eye. CT images showed a neoplastic lesion that invaded to the maxillary sinus and orbital cavity, with the left pterygopalatine fossa as the principal site, and also showed contrast effects. To obtain a definitive diagnosis from histopathological analysis, the lesion was biopsied, and she was diagnosed as the inflammatory pseudotumor with the immunohistochemical study and multiplex polymerase chain reaction-based clonality assays. The patient had a lymphoid-predominant lesion that responded to radiotherapy but corticosteroids were not effective. It is important to scrutinize the pathology to avoid unnecessary and mutilating surgery.

Intra-Adenoid Cyst: A Case Report with an Immunohistochemical Study and Review of Literature.

A woman in her 50s was referred to our department with the chief complaint of nasal congestion and pharyngeal discomfort. The patient had been diagnosed with sleep apnea at the Department of Internal Medicine, and had undergone nasal continuous positive airway pressure (nCPAP) therapy, but her response to the treatment was poor. A cystic lesion occupying the nasopharynx, which was detected by nasopharyngeal fiberscopy, computed tomography, and magnetic resonance imaging, was thought to be the cause of the nasal congestion, pharyngeal discomfort, and obstructive sleep apnea syndrome (OSAS). Consequently, the patient underwent extirpation of the lesion under general anesthesia for the purpose of obtaining a definitive diagnosis as well as for treatment of the nasopharyngeal tumor. The diagnosis of intra-adenoid cyst was eventually made based on the pathological findings, which revealed lymphoid tissue accompanied by expansion of the crypt, as well as inflammatory cell infiltration with follicular hyperplasia. After the operation, the patient reported subjective improvement of her symptoms, and began to respond to the nCPAP therapy for her sleep apnea syndrome. Nasopharyngeal cysts, in particular adult intra-adenoid cyst, are relatively rare. The outcomes of the current case indicated that the presence of a nasopharyngeal cystic disease was hampering the nCPAP treatment of refractory OSAS.