Dilated Intercellular Spaces in Eosinophilic Esophagitis

2014 ◽  
Vol 59 (5) ◽  
pp. 589-593 ◽  
Author(s):  
Alberto Ravelli ◽  
Vincenzo Villanacci ◽  
Moris Cadei ◽  
Maurizio Fuoti ◽  
Giada Gennati ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tetsuo Shoda ◽  
Kenneth M. Kaufman ◽  
Ting Wen ◽  
Julie M. Caldwell ◽  
Garrett A. Osswald ◽  
...  

AbstractEosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease with a complex underlying genetic etiology. Herein, we conduct whole-exome sequencing of a multigeneration EoE pedigree (discovery set) and 61 additional multiplex families with EoE (replication set). A series of rare, heterozygous, missense variants are identified in the genes encoding the desmosome-associated proteins DSP and PPL in 21% of the multiplex families. Esophageal biopsies from patients with these variants retain dilated intercellular spaces and decrease DSP and PPL expression even during disease remission. These variants affect barrier integrity, cell motility and RhoGTPase activity in esophageal epithelial cells and have increased susceptibility to calpain-14–mediated degradation. An acquired loss of esophageal DSP and PPL is present in non-familial EoE. Taken together, herein, we uncover a pathogenic role for desmosomal dysfunction in EoE, providing a deeper mechanistic understanding of tissue-specific allergic responses.


Light and electronmicroscopic observations of changes throughout the small intestine of foetal, and both suckled and unsuckled newborn pigs are reported. Foetal animals between 73 days gestation and term showed vacuolation in the terminal ileum. This was most extensive between 90 and 100 days when the terminal 30% of the small intestine contained vacuolated cells. The apical region of such cells contained a system of smooth tubes and vesicles, some of which showed evidence of a characteristic surface pattern. The vacuoles contained material of variable electron density and were sometimes seen apparently discharging their contents into the dilated intercellular spaces. Unsuckled newborn animals showed most of the features described above, but, in addition, the vacuolated cells contained large numbers of electron dense inclusions. In suckled animals from birth to 70 h of age there were considerable variations in cellular structure, which could be related to the position in the small intestine, the position on the villus and the age of the animal. The structural features described are discussed in relation to the transfer of colostrum immunoglobulins into the circulation. Keywords: swine, foetus, newborn, small intestine, structure.


2006 ◽  
Vol 42 (5) ◽  
pp. 510-515 ◽  
Author(s):  
Alberto M. Ravelli ◽  
Vincenzo Villanacci ◽  
Nella Ruzzenenti ◽  
Piergiovanni Grigolato ◽  
Pamela Tobanelli ◽  
...  

2008 ◽  
Vol 21 (8) ◽  
pp. 757-764 ◽  
Author(s):  
N. A. Tobey ◽  
T. M. Gambling ◽  
X. C. Vanegas ◽  
J. L. Carson ◽  
R. C. Orlando

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