Separation and characterization of nonphosphorylated and serine-phosphorylated urokinase. Catalytic properties and sensitivity to plasminogen activator inhibitor type 1.

Urokinase synthesized by human A431 epidermoid carcinoma cells is phosphorylated on serine (Mastronicola, M. R., Stoppelli, M. P., Migliaccio, A., Auricchio, F., and Blasi, F. (1990) FEBS Lett. 266, 109-114). To test the possibility that phosphorylation may have specific effects on urokinase function, the phosphorylated and nonphosphorylated forms of urokinase were separated by Fe(3+)-Sepharose chromatography. Both forms exhibit indistinguishable Km and kcat for plasminogen activation. On the other hand, their sensitivity toward the specific plasminogen activator inhibitor type 1 is different as assessed by measuring both the stability of the covalent complex and the residual enzymatic activity. Phosphorylated urokinase was 50% inhibited at a concentration of plasminogen activator inhibitor type 1 4-fold higher than nonphosphorylated urokinase (0.7 versus 0.15 nM). Furthermore about 10% of phosphorylated urokinase was resistant to plasminogen activator inhibitor type 1 at a concentration as high as 20 nM. Thus, phosphorylation affects urokinase sensitivity to plasminogen activator inhibitor type 1, therefore resulting in a net, although indirect, increase of urokinase activity. These results suggest the existence of a novel cellular regulatory mechanism of extracellular proteolysis

Partial pharyngolaryngectomy with infrahyoid flap: Our experience

Aim: We evaluated a cohort of advanced hypopharyngeal squamous cell carcinoma, treated with conservative surgery, reconstruction with infrahyoid flap and radio-chemotherapy. Methods: We used partial pharyngo-laryngectomy and radio-chemotherapy to treat fifty-seven patients with stage III–IV hypopharyngeal SCC from November 1994 to December 2011. Clinical examination and speech therapy evaluation were used for estimation of laryngeal function. Results: All patients received a partial pharyngo-laryngectomy. All patients underwent neck dissection; 56 patients received bilateral neck dissection. Reconstruction was achieved by infra-hyoid flap. Five-year overall and disease-specific survival rates were 54.4% and 61.4%, respectively. Successful laryngeal function preservation with complete five-year remission was achieved in 44% of the patients. Conclusion: Selected even if advanced carcinomas of the hypopharynx maybe treated with partial pharyngo-laryngectomy with reconstruction with pedicled flap. Both oncological and functional results showed a good outcome

Transit time of swallowing after subtotal laryngectomy

Introduction: The aim of subtotal laryngeal surgery (Cricohyoidopexy= CHP and Cricohyoidoepiglottopexy= CHEP) is to create a simplified but functional neolarynx. The neolarynx permits the passage of air, the closure of the airway, and ensures phonation through the vibration of the cricoid and arytenoid mucosa; furthermore, it allows the recovery of shallowing, optimizing the closure of the neoglottis with the movement of the remaining arytenoids. The aim of the present study was to evaluate, on a long term basis, the efficiency of the swallowing function comparing swallowing times in CHEP and CHP with and without functional neck dissection (FND). Materials and methods: A radiological study was conducted on 48 patients selected from a group of 253, who underwent subtotal laryngectomies at the "G. Ferreri" Department of Otorhinolaryngology, Audiology and Phoniatrics of the University of Rome "La Sapienza". The selection of the 48 patients was carried out based on the following criteria: type of surgery, date of surgery (follow up of at least 12 months), patients who were not treated with radiotherapy before or after surgery, patients who were also examined with fibrolaryngoscopy and videofluowscopy, patients not affected by motor deficits involving plwnatory and swallowing regions (stroke, lesions of the central nervous system), negative follow up (no evidence of disease). The parameters for evaluating the functional recovery were the times the nasogastric tube and tracheotomy tube were kept in place. The functional recovery-times of the groups thus formed were compared to one another. Through videofluoroscopy the authors evaluated oral transit times (OTT) and pharyngeal transit times (PTT) as parameters of deglutition. Results: The results consistently showed that swallowing time remains under one second as in individuals with normal swallowing functions. Conclusion: The study of deglutition limes, conducted at least 12 months after surgery, does not show any substantial differences between CHEP and CHP with reference to pharyngeal transit and oral transit times