Takemitsu Hama

IL-21 Administration into the Nostril Alleviates Murine Allergic Rhinitis

Type I allergic diseases such as allergic rhinitis are caused by IgE-mediated humoral immune responses, while eosinophils also fulfill important roles in the etiology of IgE-mediated allergy. IL-21 regulates growth, differentiation, and function of T, B, and NK cells, while the production of IgE is also influenced by IL-21. In this study we examined whether IL-21 is capable of controlling IgE-mediated allergic reactions in vivo by using the allergic rhinitis mouse model that was established by repetitive sensitization and intranasal challenge with OVA. Intranasal administration with recombinant mouse IL-21 (rmIL-21) significantly reduced the number of sneezes, as well as the serum concentration of OVA-specific IgE, in comparison with that of untreated allergic mice. The rmIL-21 treatment also suppressed germline Cε transcription in the nasal-associated lymphoid tissues, which may have, at least partly, resulted from the up-regulation of Bcl-6 mRNA caused by IL-21. Local expression of IL-4, IL-5, and IL-13 was also inhibited by the intranasal cytokine therapy whereas, in contrast, the expression of endogenous IL-21 mRNA was induced by exogenous rmIL-21. Moreover, IL-21 acted on nasal fibroblasts to inhibit production of eotaxin. This novel function of IL-21 may be associated with the attenuation of eosinophil infiltration into nasal mucosa that was revealed by histopathological observation. These results indicated that IL-21 nasal administration effectively ameliorated allergic rhinitis through pleiotropic activities, i.e., the prevention of IgE production by B cells and eotaxin production by fibroblasts.

A clinical study of endoscopic sinus surgery for sinusitis in patients with bronchial asthma.

Background: An association between bronchial asthma and sinusitis has long been suspected. Our aim is to study the clinical features of chronic sinusitis associated with bronchial asthma as two manifestations of one airway disease. Methods: We conducted a prospective analysis of the outcome of 88 patients, with or without bronchial asthma, who underwent endoscopic sinus surgery (ESS) for chronic sinusitis. Patients were divided into two groups by the presence or absence of asthma and were evaluated. One surgeon performed the ESS, and the same postoperative treatment was given to both groups. The postoperative outcomes of symptoms and objective findings related to sinusitis were evaluated numerically, with a maximum score of 2 points for each examination item. Twenty-eight patients with asthma symptoms were assessed before and after surgery, using peak flow (liter/second) and medication scores (according to US Food and Drug Administration) to determine whether bronchial asthma was improved by first-time ESS. Results: The outcomes of ESS were signifi- cantly worse in the asthma group, especially the endonasal findings. Patients suffering from chronic sinusitis and bronchial asthma showed improvement following ESS in terms of their asthma symptoms, peak flow and medication score. Patients with a good ESS result tended to have the greatest improvement in their asthma. Conclusions: We conclude that sinusitis and asthma are closely related to each other, acting as two manifestations of one airway disease. We recommend treating cases of sinusitis complicated by asthma as a single disease of the entire respiratory tract.

Real time in situ confocal imaging of calcium wave in the perfused whole heart of the rat

To understand the calcium handling in whole heart having automaticity of the sinus node, we have developed a system of in situ imaging the intracellular calcium ion concentration in the perfused whole heart of the rat. The system consists of a stage-fixed upright microscope equipped with a real-time confocal laser scanning device of a multipinhole type with a water-immersion objective lens for observation. This in situ imaging system rendered observations and analyses of the rapidly changing images of intracellular calcium dynamics possible in the whole rat heart loaded with fluo-3. The scanning was conducted at a video rate of 30 frames per second, and the confocal effects included both X and Y planes. Calcium waves were frequently interrupted by calcium transients from either external electro-stimulation pulses or spontaneous sinus rhythm. Our findings suggest that abnormal calcium waves in minute areas cannot disturb the excitation-contraction coupling in the whole heart if the myocardial cells have orderly end-on-end intercellular electric paths.

A 13-year Study of Japanese Cedar Pollinosis in Japanese Schoolchildren

BACKGROUND Japanese cedar pollen (JCP) sensitization and Japanese cedar pollinosis (JCPS) appear to be increasingly prevalent in younger children. The present study investigated factors affecting JCP sensitization and JCPS development in school children. METHODS In May or June each year from 1994 to 2006, 275-510 children were assessed for serum JCP-IgE and house dust mite (HDM)-IgE levels, and surveyed regarding rhinoconjunctival symptoms. RESULTS Strong JCP sensitization (IgE > or = 17.5 U(A)/ml) was associated with age (odds ratio (OR) = 2.65), the amount of dispersed pollen in the observed year (OR = 2.03) and in the year following birth (OR = 1.51), the month of birth (OR = 2.18), and the recent birth cohort (OR = 1.96). Symptoms were negatively correlated with the recent birth cohort (OR = 0.69) after adjusting for JCP-IgE levels. Strong HDM sensitization was associated with gender (OR = 0.65 for girls) and the recent birth cohort (OR = 1.76). CONCLUSIONS JCP sensitization appeared to be associated with the recent birth cohort and to increases in dispersed pollen just after birth and in the observed season. Although the recent birth cohort was more easily sensitized, they were not more likely to develop symptoms. In contrast to JCP sensitization, strong HDM sensitization appeared to develop prior to commencement of primary school and was more likely to affect boys.

Quercetin Stimulates Na+/K+/2Cl− Cotransport via PTK-Dependent Mechanisms in Human Airway Epithelium

We investigated regulatory mechanisms of Cl(-) secretion playing an essential role in the maintenance of surface fluid in human airway epithelial Calu-3 cells. The present study reports that quercetin (a flavonoid) stimulated bumetanide-sensitive Cl(-) secretion with reduction of apical Cl(-) conductance, suggesting that quercetin stimulates Cl(-) secretion by activating an entry step of Cl(-) across the basolateral membrane through Na(+)/K(+)/2Cl(-) cotransporter (NKCC1). To clarify the mechanism stimulating NKCC1 by quercetin, we verified involvement of protein kinase (PK)A, PKC, protein tyrosine kinase (PTK), and cytosolic Ca(2+)-dependent pathways. A PKA inhibitor (PKI-14-22 amide), a PKC inhibitor (Gö 6983) or a Ca(2+) chelating agent did not affect the quercetin-stimulated Cl(-) secretion. On the other hand, a PTK inhibitor (AG18) significantly diminished the stimulatory action of quercetin on Cl(-) secretion without inhibitory effects on apical Cl(-) conductance, suggesting that a PTK-mediated pathway is involved in the stimulatory action of quercetin. The quercetin action on Cl(-) secretion was suppressed with brefeldin A (BFA, an inhibitor of vesicular transport from ER to Golgi), and the BFA-sensitive Cl(-) secretion was not observed in the presence of an epidermal growth factor receptor (EGFR) kinase inhibitor (AG1478), suggesting that quercetin stimulates Cl(-) secretion by causing the EGFR kinase-mediated translocation of NKCC1 or an NKC1-activating factor to the basolateral membrane in human airway epithelial Calu-3 cells. However, the surface density of NKCC1 was not increased by quercetin, but quercetin elevated the activity of NKCC1. These observations indicate that quercetin stimulates Cl(-) secretion by activating NKCC1 via translocation of an NKCC1-activating factor through an EGFR kinase-dependent pathway.

Fibrolipoma of the parotid in a child

Fibrolipoma is a rare benign tumor found predominantly in middle and later life; it is very uncommon in children1 There are many reports in literature of resected fibrolipomas of the oral cavity.2,3 However, there are only a few reports of fibrolipoma in the parotid. This report describes a case of a S-year-old girl with fibrolipoma of the parotid gland. This is the youngest such patient to be found in the literature. lobules of yellow adipose tissue separated by white fibrous septa. No hemorrhage, necrosis, or calcification was noted. Microscopic examination of sections stained by hematoxylin and eosin showed lobules of mature adipose tissue mixed with a network of fibrous connective tissue (Fig 4). The fibrous elements contained numerous fibrocytes, suggesting the presence of mature collagen. The adipose component consisted of mature adipocytes. The histopathological features were consistent with a fibrolipoma.

Interleukin-21 as an Effective Suppressant for IgE-mediated Allergic Hypersensitivity Reactions

IgE plays essential roles in the pathogenesis of many allergic disorders including bronchial asthma, allergic rhinitis, atopic dermatitis, and anaphylaxis. If IgE production can be effectively and safely controlled in patients, such procedures may alleviate allergic symptoms, leading to novel therapeutic and prophylactic interventions of allergic diseases. Interleukin-21 (IL-21) is a cytokine produced by activated T cells. It exerts pleiotrophic immunomodulatory functions through acting on various immune cells including T, B, and NK cells. To analyze influence of exogenous IL-21 in vivo, we inserted an expression unit of IL-21 cDNA into an Epstein-Barr virus (EBV)-based artificial chromosome, so that extremely powerful and long-lasting expression of the cytokine can be achieved in vivo in the liver. Peanut anaphylactic mice were established by repetitive immunization with the crude peanut extract (CPE) as an allergen, and they received intravenous administration of the DNA construct through the tail vein under high pressure. As the results, anaphylactic symptoms were completely abrogated by the IL-21 gene treatment, in striking contrast to untreated allergic mice that showed extremely severe systemic disturbance. Serum level of IgE was also drastically suppressed by IL-21 gene treatment. Then we used recombinant IL-21 (rIL-21) to treat anaphylactic as well as allergic rhinitis mice, which also showed significant remission of the diseases. As the mechanisms of the IgE regulation, we found that expression of germ line Cepsiv transcript was suppressed in B cells that were treated with rIL-21 in vitro or in vivo, suggesting that IL-21 effectively suppressed the class switch recombination (CSR) to IgE. The present findings strongly suggest that IL-21 can be used as a novel molecular medicine to control allergy. It was also shown that the EBV-based artificial chromosome provides a useful means to analyze bioactivity in vivo of various genes in mammals, providing a platform to investigate functions of genes as well as to discover promising molecules for therapeutic molecular targeting to treat various disorders.

A Case of Embolization for Recurrent Epistaxis after Maxillary and Ethmoidal Artery Ligation.

Maxillary and ethmoidal artery ligation is generally effective for treating severe epistaxis. However, we have occasionally experienced continuous or recurrent bleeding after this procedure. We encountered a 81-year old male with severe epistaxis occuring 5 years after ligation of the internal maxillary artery and anterior ethmoidal artery. Nasal packing was not effective and angiography was performed by Seldingers method in order to confirm the site of bleeding. As a result, the reconstruction of flow to the internal maxillary artery through a collateral was found, and embolization was performed with a gelatin sponge. No further epistaxis or side effects from the embolization occurred. Therapeutic intraarterial embolization is useful for controlling severe epistaxis such as that caused by failed ligation.