Pseudomonas aeruginosa can develop resistance to polymyxin and other cationic antimicrobial peptides. Previous work has shown that mutations in the PmrAB and PhoPQ regulatory systems can confer low to moderate levels of polymyxin resistance (MICs of 8 to 64 mg/liter) in laboratory and clinical strains of this organism. To explore the role of PhoPQ in high-level clinical polymyxin resistance, P. aeruginosa strains with colistin MICs > 512 mg/liter that had been isolated from cystic fibrosis patients treated with inhaled colistin (polymyxin E) were analyzed. Probable loss-of-function phoQ alleles found in these cystic fibrosis strains conferred resistance to polymyxin. Partial and complete suppressor mutations in phoP were identified in some cystic fibrosis strains with resistance-conferring phoQ mutations, suggesting that additional loci can be involved in polymyxin resistance in P. aeruginosa. Disruption of chromosomal phoQ in the presence of an intact phoP allele stimulated 4-amino-L-arabinose addition to lipid A and induced transcription from the promoter of the pmrH (arnB) operon, consistent with the known role of this lipid A modification in polymyxin resistance. These results indicate that phoQ loss-of-function mutations can contribute to high-level polymyxin resistance in clinical strains of P. aeruginosa.

Robotic technology can be used safely to create laparoscopic microsurgical anastomoses with adequate patency rates. Robotic technology has the potential to make laparoscopic microsuturing easier.

Melanoma arises through complex genetic and epigenetic changes resulting in uncontrolled proliferation, invasion and metastatic disease. Semaphorins are critical regulators of axon guidance through interaction with their receptors, Plexins and neuropilins. Aberrant expression of Plexin receptors is been linked with progression of a variety of tumors. Plexin B1, the Semaphorin 4D receptor, activates the oncogenic receptors c-Met and ErbB-2, leading to speculation that it promotes tumor growth through stimulation of these receptors. We show that Plexin B1 is lost in metastatic melanoma and in deeply invasive primary tumors in vivo. Introduction of Plexin B1 into a human metastatic melanoma cell line suppressed proliferation, enhanced migration, stimulated Akt activation, and rendered cells resistant to cis-platin induced apoptosis. Unexpectedly, Plexin B1 inhibited c-Met by up to 54% in response to the c-Met ligand, hepatocyte growth factor, with a concordant loss of phosphorylation of the c-Met substrate, Gab1. Loss of Plexin B1 is predicted to function as a classic tumor suppressor protein in melanomas in which progression is c-Met dependent. However, because Plexin B1 activates Akt, and suppresses apoptosis, Plexin B1 likely plays a complex role in melanoma progression, and may be a predictive marker for tumor sensitivity to chemotherapeutic agents.

Optical magnification and long instrumentation significantly increase surgical tremor, which makes laparoscopic microsuturing difficult. Therefore, laparoscopic tubal anastomosis has not gained wide acceptance among gynecologic surgeons. Robotic assistance facilitates this type of procedure by filtering tremor, reducing the surgeon's fatigue, and scaling the maneuvers. The authors have successfully completed a case of laparoscopic tubal reanastomosis using a "master-slave" robot to perform the standard microsuturing technique. A 33-year-old woman, gravida 2, para 2, requested reversal of her previous tubal ligature. A right isthmic-isthmic tubal anastomosis was performed laparoscopically, with faithful adherence to the authors' standard technique applied at laparotomy. Full robotic assistance was used to anastomose the tube. A chromotubation test showed anastomotic patency without leak. The patient recovered uneventfully after surgery and was discharged within 24 h after the procedure. Laparoscopic microsurgical tubal anastomosis with full robotic assistance is feasible and safe in humans.