Examination of FERMT1 expression in placental chorionic villi and its role in HTR8-SVneo cell invasion.

Transmembrane integrin receptors mediate cell-extracellular matrix as well as cell-cell adhesion. As placental trophoblast cells undergo differentiation they display changes in integrin expression or switching, but the mechanism(s) of integrin activation that supports this differentiation is still unknown. The Fermitin family of adapter proteins (FERMT 1-3) are integrin activators that mediate integrin-mediated signaling. In this study, we examined the spatiotemporal pattern of expression of FERMT1 in human chorionic villi throughout gestation and its role in HTR8-SVneo substrate adhesion and invasion. Placental villous tissue was obtained from patients undergoing elective terminations at weeks 8-14, as well as from term deliveries at weeks 37-40 and analyzed by immunofluorescence. Additionally, HTR8-SVneo trophoblast cells were transfected with FERMT1-specific siRNA or non-targeting siRNA (control) and used in cell-substrate adhesion as well as invasion assays. FERMT1 was primarily localized to membrane-associated regions at the base or around the periphery of the villous cytotrophoblast and proximal as well as distal cell column trophoblast. FERMT1 was also localized to endothelial cells of blood vessels in chorionic villi. siRNA-mediated depletion of FERMT1 in HTR8-SVneo cells did not markedly alter HTR8-SVneo cell-substrate adhesion but did significantly decrease invasion (P < 0.05) compared to control cells. These novel findings identify the presence of the integrin activator FERMT1 in trophoblast cells and that FERMT1 can regulate HTR8-SVneo cell invasion. FERMT1 may directly influence integrin activation and the subsequent integrin-mediated signaling and differentiation that underlies the acquisition of the invasive trophoblast phenotype in vivo.

Tuberculous retroperitoneal lymphadenopathy mimicking metastatic pancreatic carcinoma.

A case of retroperitoneal lymphadenopathy of tuberculous origin is reported. Despite clear representation of retroperitoneal lym-phadenopathy by abdominal ultrasonography and computerized tomography (CT), fine-needle aspiration was inconclusive. Exploratory laparotomy was necessary to make the diagnosis. Nonsurgical diagnosis of this entity continues to be a challenge.

Erythema dyschromicum perstans.

A 29-year-old woman from Trinidad experienced the rapid onset of extensive lesions characteristic of erythema dyschromicum perstans following an x-ray study using orally administered contrast. Eleven months later a skin biopsy specimen showed few epidermal changes but extensive incontinence of melanin pigment and marked dilatation of lymphatics in the superficial dermis. Results of a systemic evaluation were normal. The available data on this disease are analyzed and conclusions offered regarding its nature and causes.

Pulmonary fibrosis associated with tracheobronchial aspiration. A study of the frequency of hiatal hernia and gastroesophageal reflux in interstitial pulmonary fibrosis of obscure etiology.

Tracheobronchial aspiration of gastric secretions has been suggested in published reports as a possible cause for idiopathic pulmonary fibrosis. Forty-eight of 131 patients with roentgenographic evidence of pulmonary fibrosis had no established etiologic diagnosis after individualized evaluations. They were prospectively studied by upper gastrointestinal series to determine the incidence of gastroesophageal reflux. The incidence of both hiatal hernia and reflux were statistically higher in the study group than in a group of 270 age-matched controls who had upper gastrointestinal series for the usual indications; (2) a subgroup of 15 patients who had pulmonary fibrosis and serologic evidence which suggested immune-mediated diseases; and (3) a subgroup of 23 patients with pulmonary fibrosis of established etiology. The patients in the study group could be further characterized by clinical and roentgenographic presentations, low maximum-mid-expiratory flow rates, and lung biopsies compatible with interstitial fibrosis. These observations and other cited evidence are supportive of the concept that repeated, small tracheobronchial aspirations of gastric acid secretions over a long period of time may cause interstitial pulmonary fibrosis.