Chronic rhinosinusitis is a heterogeneous disease. In Europe and the United States, it has recently been divided into two subgroups: chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). The majority of CRSwNP cases have a strong tendency to recur after surgery and show eosinophil-dominant inflammation. However, this definition has proved difficult to apply in Japan and East Asia, because more than half of the CRSwNP cases do not exhibit eosinophil-dominant inflammation in these areas of the world. In Japan in the 1990s, refractory CRSwNP to the standard treatment was focused on in clinical studies and the term "eosinophilic chronic rhinosinusitis" (ECRS) was introduced to identify this subgroup of chronic rhinosinusitis in 2001. ECRS is different from non-ECRS in terms of many clinical features: symptom appearance, occurrence site of nasal polyps, CT scan findings, the histology of nasal polyps, blood examination findings, clinical course after surgery, and co-morbid asthma, etc. In this review, we describe these clinical features and mention how to make a clinical diagnosis of ECRS as well as how to treat it. Finally, we discuss the pathophysiology of ECRS. The concept of ECRS in Japan would be applicable for CRSwNP in other countries including Europe and the United States.

Ultrasonography, computed tomography, and magnetic resonance imaging were performed to differentiate preoperatively between schwannomas of the vagus nerve and schwannomas of the cervical sympathetic chain by observing the position of schwannomas in regard to the surrounding blood vessels. Ultrasonography also permitted direct visualization of the vagus nerve, so its position relative to the schwannoma could be examined. In schwannomas of the vagus nerve the schwannoma grew between the common carotid artery and the internal jugular vein or between the internal carotid artery and the internal jugular vein, resulting in an increase in the distance between the artery and vein (separation). In schwannomas of the cervical sympathetic chain, no separation was observed between the internal jugular vein and the common carotid artery or internal carotid artery. Ultrasonography with a 7.5-MHz transducer showed the derivation of the tumor from the vagus nerve in schwannomas of the vagus nerve but showed the vagus nerve on the tumor surface in schwannomas of the cervical sympathetic chain.

The extracellular pH (pHe) of tumor tissues is often acidic, which can induce the expression of several proteins. We previously showed that production of matrix metalloproteinase-9 (MMP-9) was induced by culturing cells at acidic pHe (5.4 -6.5). Here we have investigated the signal transduction pathway by which acidic pHe induces MMP-9 expression. We found that acidic pHe (5.9) activated phospholipase D (PLD), and inhibition of PLD activity by 1-butanol and Myr-ARF6 suppressed the acidic pHe-induced MMP-9 expression. Exogenous PLD, but not phosphatidylinositol-specific PLC or PLA 2 , mimicked MMP-9 induction by acidic pHe. Western blot analysis revealed that acidic pHe increased the steady-state levels of phosphorylated extracellular signal-regulated kinases 1/2 and p38 and that the PLD inhibitors suppressed these increases. Using 5-deletion mutant constructs of the MMP-9 promoter, we found that the acidic pHe-responsive region was located at nucleotide ؊670 to ؊531, a region containing the NFB binding site. A mutation into the NFB binding site reduced, but not completely, the acidic pHe-induced MMP-9 promoter activity, and NFB activity was induced by acidic pHe. Pharmacological inhibitors specific for mitogen-activated protein kinase kinase 1/2 (PD098059) and p38 (SB203580) attenuated the acidic pHe-induced NFB activity and MMP-9 expression. These data suggest that PLD, mitogen-activated protein kinases (extracellular signal-regulated kinases 1/2 and p38), and NFB mediate the acidic pHe signaling to induce MMP-9 expression. A transcription factor(s) other than NFB may also be involved in the MMP-9 expression.Proteolytic degradation of extracellular matrix is important for tumor metastasis and angiogenesis. The matrix metalloproteinases (MMPs) 1 constitute a family of extracellular matrixdegrading enzymes. Among these enzymes, MMP-9/gelatinase B plays an important role in tumor invasion and metastasis because of its specificity for type IV collagen. Because the promoter region of the MMP-9 gene contains a TATA box and nuclear factor-B (NFB) and activator protein-1 (AP-1) binding sites, expression of MMP-9 mRNA can be up-regulated by stimuli such as interleukin (IL)-1 and tumor necrosis factor-␣ (1). In addition, MMP-9 expression can be up-regulated by phorbol 12-O-tetradecanoate 13-acetate through phospholipase D (PLD) (2, 3).Mitogen-activated protein kinases (MAPKs) are crucial enzymes in the receptor-mediated signaling cascade. There are three major groups of MAPKs, extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) 1/2. PD98059 and SB203580, which are specific inhibitors of MAPK kinase (MEK) 1/2 and p38, respectively, repress MMP-9 expression and in vitro tumor cell invasion (4, 5). Moreover, the JNK inhibitor SP600125 has been shown to attenuate phorbol 12-O-tetradecanoate 13-acetate-induced MMP-9 expression (6).The extracellular pH (pHe) of solid tumors is acidic due to the presence of anaerobic glucose metabolites such as lactate. For example, the basal pHe of xenograft...

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In amyotrophic lateral sclerosis (ALS) patients, dysphagia eventually occurs independent of time of onset. We studied dysphagia conditions in the early stage of ALS, principally at the oral phase. Videofluoroscopic and manometric studies were conducted on 11 patients (5 males and 6 females, age range = 47-82 years) who were diagnosed at our Neurology Clinic as having ALS. All patients were able to ingest orally. Swallowing scores on the ALS severity scale were from 10 to 5. In the oral phase of swallowing, abnormal movements of the anterior and/or posterior tongue were recognized in 8 cases. Dysphagia severity tended to be particularly influenced by dysfunction of the posterior tongue. Manometric studies were almost normal in all cases except one. These results suggested that the early stage of dysphagia in ALS was mainly caused by oral dysfunction, and the oral phase disorders began in some cases with a decreased function of bolus transport at the anterior part of the tongue, and in other cases with a deteriorated function of holding the bolus at the posterior part of the tongue. In conclusion, the tongue function of holding the bolus in the oral cavity mainly affects the severity of the early stage of dysphagia in ALS.