Search

Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method.We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities.In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%.Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully.

Background To assess the effects of Epstein–Barr virus (EBV) and human papillomavirus (HPV) infection on the tumor microenvironment, we examined the relationship between viral infection status, macrophage migration inhibitory factor (MIF), and tumor-associated macrophages in nasopharyngeal carcinoma (NPC). Methods A tissue microarray containing 150 cores from 90 patients with NPC and six with chronic inflammation was used. EBV and HPV status were detected using in situ hybridization with commercial EBER1 and HPV16/18 probes. Immunofluorescence double staining of MIF, pan-macrophage marker CD68, M1 macrophage marker CD11c, and M2 macrophage marker CD163 were analyzed using the same tissue microarray. The levels of these markers between NPC and inflammation cases and between tumor nests and stroma were compared. Correlations among these markers were analyzed. Results We found EBER1(+) cases in 90% of NPC patients, including 10% EBV/HPV co-infection. M1 macrophages mainly infiltrated the tumor nest, while M2 macrophages infiltrated the tumor stroma. We found a significant positive correlation between EBER1 levels and MIF levels in tumor nests and a significant positive correlation between HPV16/18 and CD11c(+) cell levels in NPC tissues. Conclusions It is suggested that MIF is associated with EBV, and M1 macrophage infiltration is affected by HPV status in NPC.

To determine the efficacy of endoscopic electrocauterization for pyriform sinus fistula (PSF) using a flexible Bugbee cautery electrode. From 2009 to 2016, a total of eight patients with acute suppurative thyroiditis or cervical abscess secondary to PSF were retrospectively registered in our study (three males, five females; median age 6.5 years). All patients underwent endoscopic electrocauterization as treatment for PSF. Six of eight patients had no recurrence after the initial endoscopic electrocauterization of PSF. One patient with recurrence developed symptoms 9 days after cauterization and another experienced recurrence after 2 years. Mean follow-up for the eight patients was 50 months (range 5-96 months). No post-operative complication was reported. Endoscopic electrocauterization appears to be a less-invasive, safe, and effective method for the treatment of PSF.

Clarithromycin is a 14-membered macrolide antibiotic. Low-dose, long-term macrolide therapy is effective in patients with chronic airway diseases, such as diffuse panbronchitis, chronic bronchitis, and chronic sinusitis. However, the mechanism underlying this clinical efficacy remains unclear. The dual specificity phosphatase MKP-1 (MAPK phosphatase-1), also called DUSP (dual specificity phosphatase-1), was initially identified as an in vitro ERK-specific phosphatase, but depending on the cell type, it can also dephosphorylate other members of the MAPK family, such as p38 and JNK, and thus suppress downstream signaling of these kinases. It was recently reported that MKP-1 appears to mediate the effects of several anti-inflammatory drugs, including glucocorticoids, but the role of MKP-1 on mucin gene expression in the presence of macrolides in the human airway remains unknown. Here, we demonstrate that the MKP-1 protein is induced by clarithromycin and that clarithromycin suppresses TNF-α-induced MUC5AC mucin gene expression in a p38 MAPK-dependent manner in human airway epithelial (NCI-H292) cells. Our study thus provides new insights into the role of MKP-1 in mediating the effects of macrolides and may help in the development of new therapeutic strategies against mucin overproduction.

Primary ciliary dyskinesia (PCD) is a genetic disease inherited in an autosomal recessive manner. The prevalence of PCD is estimated to be 1 in 20,000 live births. Congenital abnormality of the primary cilia results in situs inversus in 50% of patients. Decreased function of motile cilia causes chronic rhinosinusitis, otitis media with effusion, bronchiectasis and infertility. Cases with situs inversus are considered to show "Kartagener's syndrome", and diagnosis is not difficult. However, in cases without situs inversus, the diagnosis is much more troublesome. PCD without situs inversus is thus probably underdiagnosed. Prolonged chronic cough represents an important symptom that is seen in most patients. The diagnosis of PCD requires the presence of the characteristic clinical phenotypes and either: (1) specific ciliary ultrastructural defects identified by transmission electron microscopy in biopsy samples of respiratory epithelium; or (2) identification of mutation in one of the genes known to be associated with PCD. Nasal nitric oxide concentration is extremely low in PCD, and this could be useful for screening of the disease. At present, no fundamental therapies are available for PCD. Diagnosis in the early stages is important to prevent progression of bronchiectasis and deterioration of lung function by guidance for daily life, immunization, cessation of smoking and prompt therapy at the time of respiratory tract infection. Since PCD is inherited in an autosomal-recessive manner, genetic counseling is necessary after definite diagnosis.

Circulating microRNAs (miRNAs) are emerging as promising non-invasive biomarkers for human cancer. Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy worldwide, but its overall survival has remained unchanged in the past 3 decades. Biomarkers for evaluating efficacy of cancer therapy are urgently needed. To explore circulating miRNAs as cancer therapy biomarkers, we initially identified that 8 miRNAs were distinctly dysregulated in cancerous tissues compared with adjacent non-cancerous counterparts from 16 patients, using microarray and real-time PCR. Based on this discovery, the comparison study was performed between pre- and 6 months post-operative paired plasma samples on 9 patients. MiR-99a, which was down-regulated in cancerous tissues, was significantly increased in plasma after operation. Meanwhile, oncomiR miR-21 and miR-223 that were up-regulated in cancerous tissues, were significantly reduced in post-operative plasma samples. We firstly report the significant changes of miR-99a in plasma of HNSCC patients after surgery. Furthermore, plasma miR-223 was inversely increased in a patient whose cancer relapsed within 6 months after operation. We conclude that these circulating miRNAs may serve as biomarkers to evaluate the efficacy of therapy and the prognosis of HNSCC.

Oxytetracycline is a broad-spectrum antibiotic, but its nonantibacterial effects in the human respiratory tract are unknown. In this study, the effects of oxytetracycline on mucus secretion and inflammation were examined by PCR and ELISA in the human airway epithelial cell line NCI-H292. Oxytetracycline (10 μg/mL) significantly inhibited TNF-α-induced MUC5AC gene expression and MUC5AC protein levels in NCI-H292 cells. It also downregulated IL-8 and IL-1β gene expression and IL-1β protein levels. Our findings demonstrated that oxytetracycline suppressed mucus production and inflammation in human respiratory epithelial cells, providing further evidence for the usefulness of oxytetracycline for human airway inflammatory diseases.

We report a case of papillary carcinoma of the thyroid gland and cervical lymph node metastases with concurrent tuberculous lymphadenitis that was diagnosed preoperatively. A 35-year-old woman presented with multiple lymph node swellings and an anterior neck mass. No findings suggesting the coexistence of pulmonary tuberculosis were present. The patient underwent a total thyroidectomy with bilateral neck dissection together with medication. Measures to prevent tuberculosis were undertaken during the perioperative period. The histopathological diagnosis was papillary carcinoma with both metastatic and tuberculous lymphadenitis of the lymph nodes in the neck. The possible coexistence of tuberculous lymphadenitis must be ruled out when lymph node swellings are observed in patients with head and neck cancer, including thyroid carcinoma.

We investigated whether IL-33 is involved in mucus overproduction and goblet cell hyperplasia in eosinophilic chronic rhinosinusitis (ECRS). IL-33 mRNA was significantly higher in the eosinophilic CRS group than in the non-eosinophilic CRS group from human nasal polyps. IL-33 induced MUC5AC mRNA and MUC5AC protein, and also goblet cell hyperplasia at air liquid interface culture in human nasal epithelial cells. In addition to that, IL-33 induced MUC5B and FOXA3, and reduces FOXJmRNA. In conclusion, our present study demonstrated that the direct evidence of IL-33 which lead to increase mucin gene and protein expression, as well as goblet cell hyperplasia. This study provides novel insights into the role of IL-33 on mucus overproduction in eosinophilic inflammation of human airways.

Cetuximab is remarkable for the relatively high rate and severity of hypersensitivity reactions (HR) being reported in the literature. Screening for cetuximab‐specific IgE in serum via immunoassay has been found to be useful in preventing HR; however, these tests are known to have a low positive predictive rate. In an attempt to remedy this, we evaluated the interaction between cetuximab and IgE on basophils for predicting severe cetuximab‐induced HR. Twelve head and neck cancer patients were enrolled in this single‐institution study: four with a history of cetuximab‐induced HR and eight with no such history. Cetuximab‐specific and galactose‐α‐1,3‐galactose (α‐gal) specific IgEs in serum were measured in vitro using an enzyme‐linked immunosorbent assay (ELISA). IgE‐cetuximab binding on basophils was also analyzed to evaluate the decrease in cetuximab molecules on basophils after dissociation of IgE from FcεRI. The positive predictive value associated with the presence of cetuximab‐ or α‐gal‐specific IgE in serum was found to be only 0.67, whereas the negative predictive value was 1.00. On the other hand, in all four patients who developed HR, the cetuximab molecules on basophils were decreased significantly due to the dissociation of IgE from basophils (P

Objectives: Eosinophilic chronic rhinosinusitis (ECRS) is considered a refractory and intractable disease with thick mucus production, long-term nasal congestion, loss of sense of smell and intermittent acute exacerbations secondary to bacterial infections. In this study, we investigated which growth factor is deeply involved in the mucin overproduction in ECRS. Method: We employed fluorescence immunohistochemical analysis to evaluate whether or not TGF-α expression was upregulated in the nasal tissue of ECRS patients. We also examined MUC5AC transcription using a luciferase reporter plasmid in HM3-MUC5AC cells and A549 cells in order to assess the role of TGF-α in human epithelial cells. Results: TGF-α immunoreactivity was found markedly increased in the submucosal tissue in the ECRS patient compared with that of a normal patient and with noneosinophilic CRS. TGF-α synergized with TNF-α to upregulate MUC5AC expression in human epithelial cells through the ERK signaling pathway. Conclusion: Our results demonstrated that TGF-α was highly expressed in the upper airway tract in ECRS patients and is deeply involved in mucus hypersecretion.

Background/Aims: Long-term macrolide therapy is an effective treatment for chronic sinusitis and diffuse panbronchiolitis. However, long-term use of macrolides may promote the growth of drug-resistant bacteria; therefore, development of macrolides with no antibacterial action is desirable. A new erythromycin (EM) derivative, (8R,9S)- 8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), does not possess antibacterial action. Methods: To determine whether EM900 induced a clinically relevant anti-inflammatory response and repressed mucin gene expression in cells derived from human airway epithelia, we assessed the effects of EM900 on IL-1β-induced inflammatory cytokines in A549 cells and MUC5AC gene expression in HM3-MUC5AC cells. We also investigated the effects of EM900 on IL-1β-induced NF-ĸB activation. We performed reporter gene assays and quantitative PCR in A549 and HM3-MUC5AC cells. Results: Both EM and EM900 suppressed IL-1β-induced IL-8 expression in A549 cells. EM900 also suppressed IL-1β-induced IL-1β and TNF-α expression in A549 cells. EM900 inhibited IL-1β-induced MUC5AC expression in HM3-MUC5AC cells. Both EM and EM900 suppressed IL-1β-induced NF-ĸB activation in A549 cells. Conclusion: This study demonstrated that EM900 suppressed the induction of inflammatory cytokines and MUC5AC gene expression in cells derived from human airway epithelia, and our findings indicate that these effects may be mediated by the suppression of NF-ĸB activation.

Gram-positive bacterium Streptococcus pneumoniae is an important human pathogen that colonizes the upper respiratory tract and is also the major cause of morbidity and mortality worldwide. S. pneumoniae causes invasive diseases such as pneumonia, meningitis, and otitis media. Despite the importance of pneumococcal diseases, little is known about the molecular mechanisms by which S. pneumoniae-induced inflammation is regulated, especially the negative regulatory mechanisms. Here we show that S. pneumoniae activates nuclear factor of activated T cells (NFAT) signaling pathway and the subsequent up-regulation of inflammatory mediators via a key pneumococcal virulence factor, pneumolysin. We also demonstrate that S. pneumoniae activates NFAT transcription factor independently of Toll-like receptors 2 and 4. Moreover, S. pneumoniae induces NFAT activation via both Ca2+-calcineurin and transforming growth factor-β-activated kinase 1 (TAK1)-mitogen-activated protein kinase kinase (MKK) 3/6-p38α/β-dependent signaling pathways. Interestingly, we found for the first time that tumor suppressor cylindromatosis (CYLD) acts as a negative regulator for S. pneumoniae-induced NFAT signaling pathway via a deubiquitination-dependent mechanism. Finally, we showed that CYLD interacts with and deubiquitinates TAK1 to negatively regulate the activation of the downstream MKK3/6-p38α/β pathway. Our studies thus bring new insights into the molecular pathogenesis of S. pneumoniae infections through the NFAT-dependent mechanism and further identify CYLD as a negative regulator for NFAT signaling, thereby opening up new therapeutic targets for these diseases.

Fish bones as a foreign body are often present in the palatine tonsil and the base of the tongue. Such foreign bodies can often be diagnosed with inspection only. However, it is difficult to diagnose and extirpate a foreign body when it is buried in the oral/pharyngeal mucosa. We experienced a case of a fish bone foreign body buried in the tongue muscle layer. We report herein on the case of a 49-year-old man with a fish bone foreign body buried in his tongue. The patient had noticed a sore throat since eating a sea bream and was referred to our department. Visual inspection revealed no foreign body, but CT imaging revealed a fish bone in the tongue. We performed an emergency surgical exploration of tongue to locate the fish bone. Because the fish bone as a foreign body was unable to be confirmed by palpation, we identified the location of the fish bone by intraoperative CT. This is a rare case of a fish bone buried in the tongue muscle layer, and intraoperative CT was useful in identifying the positon of the foreign body.

Objectives: The purpose of the study is to know if mucin gene expression can be detected in the middle ear effusion and if so, which mucin genes are expressed in the effusions. Methods: Mucin gene expression in the middle ear effusions obtained from five patients with otitis media with effusion were analyzed by reverse transcription-polymerase chain reaction. Ribonucleic acids (RNAs) were extracted from the effusion and the expression of 12 mucin genes was analyzed by reverse transcription-polymerase chain reaction. Results: Mucin gene expression examined by reverse transcription-polymerase chain reaction indicated the expression of MUC1 , MUC4 , MUC5AC , MUC6 , MUC7 , MUC8 , MUC9 , MUC11 and MUC12 mRNA in the effusion. This mucin gene expression was similar to that in BEAS-2B cell, a bronchial epithelial cell line. Conclusion: Middle ear effusion can give us valuable information on mucin gene expression in the middle ear. There is similarity between mucin gene expression in the middle ear effusion and that in the bronchial epithelia.

Objective To clarify 1) which mucin gene expression is influenced by glucocorticoid and 2) whether glucocorticoid influences steady-state mucin expression or mucin gene expression induced by lipopolysaccharide. Methods Dissociated cells obtained from nasal polys were cultured on a collagen gel substrate in an air-liquid interface. Dexamethasone was added to the culture medium in the steady-state and prior to the stimulation by LPS. RNAs were extracted from culture cells, and semiquantitative reverse transcriptase-polymerase chain reaction was performed for MUC2, MUC5AC, MUC5B, MUC8, and β-actin. Results Dexamethasone did not influence steady-state messenger RNA levels of either mucin gene. Dexamethasone suppressed lipopolysaccharide-induced messenger RNA levels of MUC8. Conclusion Glucocorticoid does not influence steady-state mucin gene expression but suppresses mucin gene expression induced by secretagogues such as lipopolysaccharide.

Background Pendred's syndrome (PS) is an autosomal recessive disorder characterized by goiter and congenital sensorineural hearing loss. Recent advances in molecular biology revealed the gene responsible for PS (PDS) and provided an important aid for the diagnosis of this condition. Methods A case of PS with huge goiter and congenital hearing impairment was diagnosed by mutational analysis of the PDS gene. Results Physical examination and computer tomography CT revealed a diffuse swelling of the thyroid gland. Thyroid function tests were normal, and the perchlorate discharge test was negative. Audiologic examination confirmed sensorineural hearing loss, and temporal bone CT revealed bilateral enlarged vestibular aqueducts. The mutational analysis revealed that the patient was homozygous for His 723 Arg (2168AG) in exon 19, a missense mutation. Conclusions The results of thyroid function tests in PS patients are usually normal, and the positive perchlorate discharge test has been used for the diagnosis. However, this is a nonspecific test and is not sensitive enough for PS. In our case, despite a negative perchlorate test, the patient was diagnosed by mutational analysis and received total thyroidectomy to relieve respiratory distress caused by thyroid enlargement. This is the first report of a mutation detected in the thyroid tissue and clearly shows that the mutation caused histopathologic change in that gland. © 2002 Wiley Periodicals, Inc.

To clarify long-term outcome of benign paroxysmal positional vertigo (BPPV), 50 patients were followed up for a mean of 52 months. Overall recurrence rate by Kaplan-Meier estimation was 37% at 60 months. The patients with horizontal canal BPPV (n = 19) had a significantly higher recurrence rate (50%) at 60 months than those with posterior canal BPPV (n = 28; 26%). There was no significant association between recurrence rates and sex or age.

Background: Interleukin-31 (IL-31) is a newly discovered T helper lymphocyte-derived cytokine that plays an important role in allergic inflammation. However, the effects of IL-31 on mucus production in nasal allergic inflammation are completely unknown. Objective: To investigate the effects of IL-31 on mucin gene expression (MUC5AC) in patients with allergic rhinitis and in human airway epithelial cells. Methods: Expression levels of IL-31 and IL-31 receptor A (IL-31RA) were evaluated in the inferior turbinate of patients with allergic rhinitis and non-allergic rhinitis with immunohistochemistry. IL-31-induced MUC5AC gene expression was measured with a MUC5AC luciferase reporter assay in human epithelial HM3-MUC5AC cells and quantified by quantitative real-time polymerase chain reaction in human airway epithelial A549 cells. Results: IL-31RA was primarily localized in submucosal glands and upregulated in allergic rhinitis. IL-31 was detected in submucosal tissue and increased in allergic inflammation. MUC5AC gene expression was induced by IL-31 stimulation both in HM3-MUC5AC and A549 cells. Additionally, IL-31 cooperated with Th2 cytokines on MUC5AC gene expression in HM3-MUC5AC cells. Conclusion: IL-31 and IL-31RA are upregulated in patients with allergic rhinitis, and induce MUC5AC gene expression in human airway epithelial cells. These findings suggest that IL-31 plays an important role in mucus overproduction in nasal allergic inflammation.

This study aims to identify predisposing characteristics of descending necrotizing mediastinitis (DNM) arising from deep neck infection (DNI) and to determine appropriate therapeutic intervention strategies. We retrospectively reviewed 54 patients (male, n = 34; female, n = 20; mean age, 64.5 years) who had been treated at Mie University Hospital for DNI between April 2001 and October 2011. Eight of nine patients who developed DNM confirmed by computed tomography of the neck and chest, underwent mediastinal drainage (video-assisted thoracic surgical drainage, n = 6; mediastinoscopy-assisted drainage, n = 2). A patient developed uncontrolled acute respiratory distress syndrome after aggressive surgery, resulting in a mortality rate of 12 %. High blood CRP values, and the pharynx and tonsils as origins of infection were factors involved in the development of DNM arising from DNI. In conclusion, DNM remains a destructive and fatal disease that requires aggressive treatment including mediastinal exploration.

The TGF-beta (transforming growth factor-beta) pathway represents an important signalling pathway involved in regulating diverse biological processes, including cell proliferation, differentiation and inflammation. Despite the critical role for TGF-beta in inflammatory responses, its role in regulating NF-kappaB (nuclear factor-kappaB)-dependent inflammatory responses still remains unknown. In the present study we show that TGF-beta1 synergizes with proinflammatory cytokine TNF-alpha (tumour necrosis factor-alpha) to induce NF-kappaB activation and the resultant inflammatory response in vitro and in vivo. TGF-beta1 synergistically enhances TNF-alpha-induced NF-kappaB DNA binding activity via induction of RelA acetylation. Moreover, synergistic enhancement of TNF-alpha-induced RelA acetylation and DNA-binding activity by TGF-beta1 is mediated by PKA (protein kinase A). Thus the present study reveals a novel role for TGF-beta in inflammatory responses and provides new insight into the regulation of NF-kappaB by TGF-beta signalling.

Transforming growth factor-beta (TGF-beta) family members are multifunctional growth factors involved in regulating diverse biological processes. Despite the critical role for TGF-beta in regulating cell proliferation, differentiation, migration and development, its role in regulating NF-kappaB-dependent inflammatory response still remains unclear. Here, we show that TGF-beta1 induces acetylation of NF-kappaB p65 subunit to synergistically enhance bacterium nontypeable Haemophilus influenzae-induced NF-kappaB activation and inflammatory response in vitro and in vivo. The TGF-beta1-induced acetylation of p65 is mediated via a Smad3/4-PKA-p300-dependent signaling pathway. Acetylation of p65 at lysine 221 by TGF-beta1 is critical for synergistic enhancement of bacteria-induced DNA-binding activity, NF-kappaB activation, NF-kappaB-dependent transcription of TNF-alpha and IL-1beta and interstitial polymorphonuclear neutrophil infiltration in vitro and in vivo. These studies provide new insights into the novel regulation of NF-kappaB by TGF-beta signaling.

In review of the past studies on NF-kappaB regulation, most of them have focused on investigating how NF-kappaB is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-kappaB and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-kappaB-dependent inflammatory response via activation of multiple signaling pathways in vitro and in vivo. The classical IKKbeta-IkappaBalpha and p38 MAPK pathways are involved in synergistic activation of NF-kappaB via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-kappaB via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-kappaB-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases.

The transforming growth factor beta (TGF-beta) pathway represents an important signaling pathway involved in the regulation of diverse biological processes, including cell proliferation, differentiation, and apoptosis. Despite the known role of TGF-betaR-mediated signaling in suppressing immune response, its role in regulating human Toll-like receptors (TLRs), key host defense receptors that recognize invading bacterial pathogens, however, remains unknown. Here, we show for the first time that TGF-betaR-Smad3/4 signaling pathway acts as a positive regulator for TLR2 induction by bacterium nontypeable Hemophilus influenzae (NTHi) in vitro and in vivo. The positive regulation of TLR2 induction by TGF-betaR is mediated via a dual mechanism involving distinct signaling pathways. One mechanism involves functional cooperation between the TGF-betaR-Smad3/4 pathway and NF-kappaB pathway. Another involves MAP kinase phosphatase 1 (MKP-1)-dependent inhibition of p38 MAPK, a known negative regulator for TLR2 induction. Moreover, we showed that TbetaR-mediated signaling is probably activated by NTHi-derived TGF-beta mimicry molecule via an autocrine-independent mechanism. Thus, our study provides new insights into the role of TGF-beta signaling in positively regulating host defense response by tightly controlling the expression level of TLR2 during bacterial infections and may lead to new therapeutic strategies for modulating host defense and inflammatory response.

Malignant external otitis is a severe infection of the external auditory canal, generally caused by Pseudomonas aeruginosa in elderly diabetics patients. We describe a case of malignant external otitis in a 63-year-old man with severe otalgia, purulent otorrhea and polypoid granulation of the external auditory canal. Local debridement, insulin treatment and 6-week intravenous antibiotic therapy with carbapemens were very effective and the granulation tissue disappeared completely. However, the patient readmitted for recurrent disease 3 weeks later, despite the oral and ear drop administration with new quinolone. No recurrence has been noted after 4-week additional treatment with intravenous carbapenems followed by 3-week treatment with Burow's solution as ear drops.

We describe a rare case of high-pressure grease injury of the face in a 48-year-old man with severe facial edema, soft palate swelling, and bleeding from the nose and mouth. Preoperative computed tomography (CT) revealed multiple low-density areas in nasal cavity, subcutaneous tissue of the cheek, soft palate, right maxillary sinus, and right infratemporal fossa. The patient complained of a dyspnea feeling, and immediate tracheostomy was performed. The grease was removed by the Caldwell-Luc incision approach but was partially left in the infratemporal fossa. After the operation, the patient still complained cheek and temporal pain. CT and magnetic resonance imaging were useful to diagnose the remaining grease, and the remnant of the grease was completely removed by the Weber-Fergusson incision approach.

Pranlukast is a selective cysteinyl leukotriene(1 )(cysLT(1)) receptor antagonist, and is now widely used in the treatment of asthma. The anti-asthmatic effect of pranlukast may be rendered not only by antileukotriene activity, but also by other pharmacological activity. This study was designed to investigate whether pranlukast had inhibitory effects on nuclear factor-kappaB (NF-kappaB) activation and mucin gene expression in cultured human epithelial cells. Luciferase assay was mainly used for analysis. Cultured epithelial cells were transfected with NF-kappaB luciferase vector, MUC2 or MUC5AC luciferase vectors. Lipopolysaccharide (LPS) significantly increased NF-kappaB activation in NCI-H292 cells, which was inhibited by the pretreatment by pranlukast in a dose-dependent manner. Either LTD(4) or pranlukast alone did not increase NF-kappaB activation in NCI-H292 cells. Pranlukast also inhibited NF-kappaB activation induced by phorbol 12-myristate 13-acetate (PMA). Pranlukast also significantly inhibited LPS-induced MUC2 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) analysis in NCI-H292 cells. Pranlukast also inhibited LPS-induced MUC2 gene expression in HM3-MUC2 cells. However, pranlukast did not inhibit MUC5AC gene transcription activity induced by lipoteichoic acid (LTA) in NCI-H292 cells. These results suggest that pranlukast may inhibit NF-kappaB activation and MUC2 gene transcription through pathways distinct from cysLT(1) receptor antagonism in cultured human epithelial cells.

Macrolide antibiotics are believed to inhibit mucus secretion but the mechanism of action is unclear. This study was designed to investigate an effect of roxithromycin on MUC2 gene expression in cultured intestinal epithelial cells (HM3-MUC2 cells). A reporter gene assay was used for analysis. Roxithromycin suppressed MUC2 gene transcriptional activity in a dose-dependent manner in HM3-MUC2 cells. Phorbol 12-myristate 13-acetate (PMA), lipoteichoic acid (LTA), lipopolysaccharide (LPS) and leukotriene D4 (LTD4) significantly increased MUC2 luciferase activities in the following order: PMA > LTA > LTD4 > LPS. Roxithromycin also decreased MUC2 gene transcriptional activity induced by PMA in a dose-dependent manner. NF-ĸB activation, but not AP-1 activation, was significantly suppressed by roxithromycin in HM3-MUC2 cells. A suppression of NF-ĸB activation was also observed in NCI-H292 cells. These results suggest that roxithromycin suppresses MUC2 gene expression in epithelial cells and that this suppression is probably via inhibition of NF-ĸB activation.

We reported a case of thyroglossal duct cancer, which metastasized to the bilateral cervical lymph nodes. The cervical lymph node metastases were detected in the upper portion of the neck. According to the results obtained in the preoperative fine needle aspiration cytology, the lymph node metastases were classified as group V and a diagnosis of papillary carcinoma was made. The preoperative studies with 123 I revealed no concentration in the submittal tumor. In our surgical procedure, bilateral supraomohyoid neck dissection was added to excision of the tumor. Conclusion: In view of the fact that thyroglossal duct cancer metastasized bilaterally to cervical lymph nodes in the present case, we experienced an extremely rare case.

Background: Airway epithelial cells produce cytokines and participate in the regulation of mucosal immunity. Although nasal epithelial cells express histamine receptors, it is not exactly known how nasal epithelial cells respond to histamine. Objective: The objective of this study was to examine whether histamine can alter the expression of the 4 genes encoding H 1 receptor, IL-8, TNF-α, and ZO-1 tight-junction protein in cultured nasal epithelial cells. Methods: We added histamine or vehicle to cultured human nasal epithelial cells and extracted RNA from them 4 hours later. After DNase treatment, mRNAs of β-actin, H 1 receptor, IL-8, TNF-α, and ZO-1 tight-junction protein were amplified by using RT-PCR. Results: Histamine significantly upregulated IL-8 mRNA expression and significantly downregulated ZO-1 mRNA expression. The latter effect was blocked by pretreatment with mepyramine, an H 1 receptor antagonist. Conclusion: The reduction of ZO-1 mRNA by histamine may cause increased permeability of the mucosa during allergic reactions in the nose. (J Allergy Clin Immunol 2001;107:310-4.)

Postoperative parathyroid function was evaluated in 24 total thyroidectomy and 8 subtotal thyroidectomy patients seen by our department between January 1995 and July 1997. Parathyroid function was assessed by measuring the level of serum intact parathyroid hormon (intact-PTH). Hypoparathyroidism was avoided in 23 patients (95.8%) who received a total thyroidectomy and in 7 patients (87.5%) who received a subtotal thyroidectomy. Supplementary therapy for hypoparathyroidism was not required as long as the blood supply to more than two parathyroid glands was preserved. Half of the patients in this study did not require any postoperative supplementary therapy. Thus, the preservation of more than two parathyroid glands is essential for the prevention of hypoparathyroidism. In cases where the parathyroid glands had been resected, parathyroid gland transplantation were performed. In all cases, supplementary therapy was eventually no longer required. In two cases requiring supplementary therapy, a normal range of parathyroid activity was observed 30 months after surgery. The administration of vitamin D3 may suppress the recovery of parathyroid function in patients recieving parathyroid transplantations.

In our hospital, ultrasonography is performed for patients who come for thyroid cancer screening. Seventy-eight patients with thyroid cancer which was found by such screening were operated on from 1989 to 1998, while 287 patients with thyroid cancer found by other methods were operated on during the same period in our department. The age of the patients at surgery in the screening group was younger than that of the contrast group. In the screening group, 41 (52.6%) patients had small thyroid cancer, a higher rate that in the contrast group. Invasion of surrounding organs by the primary cancer was observed in only one patient (1.3%) in the screening group, a rate of invasion that was statistically lower than that in the contrast group. Twenty-six patients with benign thyroid disease detected in our screening were operated on during the same period. Careful selection of patients who need fine-needle aspiration cytology is demanded of head and neck surgeons, and careful evaluation of indicators is necessary to avoid surgery in the case of benign thyroid disease.

During a 66-month period, 2849 patients with thyroid gland tumor were examined by fine needle aspiration cytology (FNA) under ultrasonographic imaging at Yamada Red Cross Hospital. Of these patients, 333 received surgical therapy and histological examinations were performed. FNA yielded an accuracy of 92.4%, a specificity of 100% and a sensitivity of 88.3%. There were 16 false-negative reports which were mainly considered to be due to calcified lesions, cystic lesion, or follicular carcinoma. Among the 188 negative cases, 24 cases (12.8%) proved to be positive by repeated FNA-Preoperative FNA provides cytological information and may assist in the determination of the operative indication. This approach resulted in an increased rate of surgery of thyroid malignancies among all thyroid gland surgeries. This method need to be improved to reduce false-negative results and the combination of FNA diagnosis and other examination is necessary.