Allergic rhinitis (AR), the most common allergic disorder of the airway, is often accompanied by bronchial asthma. However, little is known about the mechanism by which AR advances to AR comorbid with bronchial asthma (AR+Asthma). To determine the pathophysiologic features of AR and AR+Asthma, we examined subsets of follicular helper T (Tfh) cells and regulatory B (Breg) cells in peripheral blood from AR and AR+Asthma patients. The results showed polarization of Tfh2 cells within Tfh cell subsets in both AR and AR+Asthma cases. Interestingly, the %Breg cells in total B cells were decreased in AR cases and, more extensively, in AR+Asthma cases. Moreover, we found significant correlations of fractional exhaled nitric oxide and blood eosinophil levels with the index %Tfh2 cells per %Breg cells. Our findings indicate that relative decrease in Breg cells under the condition of Tfh2 cell skewing is a putative exaggerating factor of AR to bronchial asthma.

We develop a chiral SU(3) symmetric relativistic mean field model with a logarithmic potential of scalar condensates. Experimental and empirical data of symmetric nuclear matter saturation properties, bulk properties of normal nuclei, and separation energies of single-and double-hypernuclei are well explained. The nuclear matter equation of state (EOS) is found to be softened by σ ζ mixing which comes from determinant interaction. The neutron star matter EOS is further softened by hyperons.

Papillary thyroid carcinoma (PTC) is a well-differentiated endocrine malignant tumor that develops from thyroid follicular epithelium. The tumor represents the most common type of endocrine malignancy; however, its tumorigenesis is not fully elucidated. The aim of this study was to address the functional role of the sorting nexin (SNX) family in PTC because of recent experimental evidence suggesting that the SNX family members actively control endocytotic transportation as well as cell fate. Expression profiles of SNX family members of PTC showed a significant quantity of transcripts of SNX5. Further immunohistochemical analysis with an SNX5-specific monoclonal antibody established in this study consistently demonstrated the preferential expression of SNX5 in PTC (94.2%, 113/120 cases) as indicated by studies on 440 cases of various tumors. In contrast, other major carcinomas originating from the lung (2.6%, 1/38 cases), breast (5.1%, 2/39 cases), and intestine (4.2%, 1/24 cases) scarcely expressed SNX5. When we investigated models of murine thyroid tumors induced by the administration of carcinogens, high expression of Snx5 was also observed in well-differentiated thyroid tumors, further implying that the tumorigenesis of the thyroid gland was tightly associated with the abundance of SNX5/Snx5. Moreover epithelial cells expressing excess SNX5 showed high levels of Caspase-2 of an initiator caspase. Collectively these findings suggest that the evaluation of SNX5 expression would support pathological diagnosis of primary and secondary PTC. (Cancer Sci 2012; 103: 1356-1362 T he thyroid gland, controlling energy production and many metabolic pathways, is the most common site for the development of malignant tumors among a variety of endocrine organs.(1) The proportion of malignant thyroid tumors has steadily increased over the last three decades.(2-4) Most thyroid tumors originate from thyroid follicular epithelial cells known as thyrocytes and exhibit various histopathological subtypes, of which papillary thyroid carcinoma (PTC) comprises the predominant subtype, with a female:male ratio of about 3:1. While PTC generally has a favorable prognosis, the tumor can potentially metastasize to regional lymph nodes, the lung and other organs.(5-8) Pre-existing benign thyroid lesions and ionizing radiation are known risk factors, and gene alterations such as BRAF and RAS point mutations, and RET/PTC and TRK gene rearrangements have been reported in PTC. (9)(10)(11)(12)(13) Gene regulatory factors making critical contributions during the development of thyrocytes are of diagnostic value for PTC in the pathologic laboratory, including thyroid transcription factors including TTF-1 and TTF-2, a hematopoietically expressed homeobox (HHEX), and paired box gene-8 (PAX8). (14)(15)(16)(17) However, the etiology of the tumor development has not been fully clarified.Thyrocytes synthesize the thyroid hormones through a multiple intracellular process coordinated by thyroid-stimulating hormone. During the process, a transcytotic pathwa...

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Thyroid carcinoma is the most common endocrine malignancy and its prevalence has recently been increasing worldwide. We previously reported that the level of sorting nexin 5 (Snx5), an endosomal translocator, is preferentially decreased during the progression of well-differentiated thyroid carcinoma into poorly differentiated carcinoma. To address the functional role of Snx5 in the development and progression of thyroid carcinoma, we established Snx5-deficient (Snx5 ) mice. In comparison to wild-type (Snx5 ) mice, Snx5 mice showed enlarged thyroid glands that consisted of thyrocytes with large irregular-shaped vacuoles. Snx5 thyrocytes exhibited a higher growth potential and higher sensitivity to thyroid-stimulating hormone (TSH). A high content of early endosomes enriched with TSH receptors was found in Snx5 thyrocytes, suggesting that loss of Snx5 caused retention of the TSH receptor (TSHR) in response to TSH. Similar data were found for internalized EGF in primary thyrocytes. The increased TSH sensitivities in Snx5 thyrocytes were also confirmed by results showing that Snx5 mice steadily developed thyroid tumors with high metastatic potential under high TSH. Furthermore, a thyroid cancer model using carcinogen and an anti-thyroidal agent revealed that Snx5 mice developed metastasizing thyroid tumors with activation of MAP kinase and AKT pathways, which are postulated to be major pathways of malignant progression of human thyroid carcinoma. Our results suggest that thyrocytes require Snx5 to lessen tumorigenic signaling driven by TSH, which is a major risk factor for thyroid carcinoma. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.