The Effect of Pemphigus Sera on Apoptosis of Keratinocytes / 대한피부과학회지

BACKGROUND: Pemphigus is an autoimmune blistering disease of skin and mucous membrane characterized by loss of adhesion between keratinocytes, a process known as acantholysis. The target molecules of autoantibodies are desmogleins which belong to cadherin family proteins of desmosome. Independently from the autoantibodies involved, the question whether apoptosis plays a role in the pathogenesis of pemphigus has not been addressed. OBJECTIVES: The purpose of this study was to determine if pemphigus sera induce apoptosis in HaCaT cells and to elucidate the mechanism of apoptosis induced by pemphigus sera. METHODS: We treated pemphigus sera on HaCaT cells for 48h and investigated whether apoptosis was induced or not through FACS analysis and TUNEL staining. In addition, we performed western blot analysis to detect cleavage of PARP, cytosolic cytochrome c and activation of caspase-8, 3, which play a major role in apoptosis. Soluble Fas ligand protein level in pemphigus sera was compared with the level in normal sera by ELISA. Pemphigus sera from which IgG was eliminated, were treated on HaCaT cells to elucidate the role of IgG in pemphigus sera-induced apoptosis. RESULTS: Using FACS analysis with Annexin-V and PI staining, we have shown that pemphigus sera induced apoptosis in HaCaT cells. TUNEL staining assay also confirmed the apoptosis were induced in HaCaT cells after treatment of pemphigus sera. Western blot analysis showed activation of caspase-3, release of cytochrome c, cleavage of PARP and decrease of procaspase-8 which is proform of active caspase-8 in HaCaT cells treated with pemphigus sera. We could not detect increased Fas ligand protein level in pemphigus sera compared with the level in normal sera. Moreover, since the removal of IgG obliterated the apoptosis inducing effects of pemphigus sera in HaCaT cells, IgG might be involved in the activation of caspase-8 and caspase-3. CONCLUSION: We concluded that treatment of pemphigus serum induces the apoptosis of HaCaT cells through, at least in part, activation of caspase-8, caspase-3 and cytochrome c related mechanism, and that IgG in the pemphigus serum rather than Fas ligand is involved in the apoptosis. These results suggest that apoptosis may play an important role in the pathomechanism of pemphigus lesion.

Pulmonary Artery Sling with Situs Solitus Dextroposition of Heart and Left Superior Vena Cava

Pulmonary artery sling is a rare congenital cardiovascular anomaly which presents clinical obstructive symptoms and signs of trachea, right main bronchus and esophagus due to left pulmonary artery abnormaly arises from proximal part of right pulmonary artery. Aberrant left pulmonary artery courses to the right above right main bronchus and then turns to the left, and courses to between the anterior of the esophagus and the posterior aspect of trachea. One of important clinical significances of the pulmonary artery sling is associated with intracardiac anomalies, and with tracheal stenosis and bronchomalacia due to press tracheobronchial tree by the aberrant pulmonary artery. It has been thought that embryological malconnection between the pulmonary artery bud from left sixth arch and the pulmonary posterior branchial plexus in the left lung bud. We had experienced 21 months old male infant with left pulmonary artery sling associated with persistent left superior vena cava and dextropostioned heart. The heart seems to move to right hemithorax due to hypoplasia or segmental atelectasis of right lung.

A case of congenital goiter with congenital hypothyroidism due to organification defect

We experienced a case of congenital goiter with congenital hypothyroidism in 45 day-old male, who complained of respiratory difficulty and anterior neck mass. After admission, he was diagnosed congenital hypothyroidism by the clinical manifestations and laboratory tests including biochemistry, radioimmunoassay, radioisotope study, perchlorate discharge test, and bone radiography. We obtained positive finding at the perchlorate discharge test and found that his congenital goiter with congenital hypothyroidism was manifested by organification defect. We started treatment with L-thyroxine orally at 6th hospital day. The case was presented with brief review of literatures.