Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication.IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are able to protect infants from severe disease, if administered prophylactically. However, antibody responses established after natural RSV infections are poorly protective against reinfection, and high levels of antibodies do not always correlate with protection. Therefore, RSV might be capable of interfering, at least partially, with antibody-induced neutralization. In this study, a process through which surface-expressed RSV F proteins are internalized after interaction with RSV-specific antibodies is described. One the one hand, this antigen-antibody complex internalization could result in an antiviral effect, since it may interfere with virus particle formation and virus production. On the other hand, this mechanism may also reduce the efficacy of antibody-mediated effector mechanisms toward infected cells.

Management of ruptures complicating angioplasty and stenting of supraaortic arteries: report of two cases and a review of the literature.

Vessel rupture is a rare complication of angioplasty and stent placement of the supraaortic arteries occurring in two (1.1%) of 180 vessels treated at our institution. Many different approaches to the management of this complication have been proposed. In this report, we present our experience with conservative management in two cases in which vessel rupture occurred and review the relevant literature.

Management of neuroform stent dislodgement and misplacement.

A self-expanding stent has recently been introduced for the treatment of wide-neck aneurysms. We describe two cases of stent malposition within large aneurysms. In the first case, the stent was dislodged during microcatheterization. This was managed by placement of a second stent through the interstices of the first followed by aneurysm coiling. In the second case, after deployment, the proximal portion of the stent moved into the aneurysm as the exchange guidewire was removed. This patient was treated by vessel sacrifice.

Transfer of a self-expanding stent to a braided microcatheter with the aid of transcatheter illumination: technical report and illustrative case.

A new self-expanding stent approved for the treatment of wide-necked intracranial aneurysms can be difficult to deploy in tortuous vascular anatomy. Some of the difficulty may be attributed to deformation of the delivery microcatheter. We describe a technique for transferring the stent into a braided microcatheter.

Ruptured aneurysm of the inferior thyroid artery: repair with coil embolization.

Although pseudoaneurysm of the thyrocervical trunk is seen with increasing frequency as a result of trauma or central venous cannulation, true aneurysm of the thyrocervical trunk is exceedingly rare. A 44-year-old woman presented with acute left neck swelling that progressed rapidly to respiratory distress and subsequent hemothorax. Emergency endotracheal intubation was performed for airway control, and tube thoracostomy was placed for drainage of the pleural space. A review of the literature reveals that this is the second patient known to be successfully treated by arterial embolization of a ruptured aneurysm of the inferior thyroid artery and the fifteenth known case of aneurysm of the inferior thyroid artery. Surgical or endovascular intervention has been successful. Observation has been uniformly fatal. Because life-threatening rupture is possible, the presence of this aneurysm mandates intervention. Endovascular coil embolization is a viable option for treatment of this entity.

The conception and development of a clinical laboratory in the group practice setting.

During the course of daily patient care, the need for clinical laboratory facilities presents itself over and over again. Many advantages can be realized by developing an in-house laboratory in the group practice setting: rapid test results, patient convenience, improved patient care, increased revenue, physician convenience, physician management, and prestige. An in-house clinical laboratory that is staffed by competent technicians, has a thorough quality control program, and is responsive to technological changes can play a very important role in the effective delivery of health care.

The relationship between plasma triglyceride concentrations and body fat content in male and female broilers--a basis for selection?

1. The relationship between plasma triglyceride concentrations and body fat content was examined in three groups of male and one of female broiler chickens fed ad libitum on a normal growing diet. 2. Phenotypic correlations between total plasma triglyceride concentration and fat content were +0.50, +0.37 and +0.39 for the three groups of male broilers and +0.33 for the group of females. Triglyceride content of plasma very low density lipoprotein (VLDL) plus low density lipoprotein (LDL) showed similar correlations with fat content. 3. Selection of birds from a flock of 550 male broilers on the basis of high or low plasma VLDL plus LDL triglyceride concentrations produced groups with significant differences in body fat content but little difference in body weight. 4. The results suggest that measurements of plasma triglyceride concentration could be used as an indirect means of selecting for decreased body fat content in broiler breeding programmes.

Nutritional effects on the growth and fatness of broilers.

1. Broiler chickens given diets high in protein, or choice-fed on a high protein balancer, had much lower abdominal fat contents than those reported in many recent experiments. The values for males were 10.8 g/kg liveweight at 56 d at 2.43 kg liveweight in one experiment in Scotland and 16.0 g/kg liveweight at 42 d at 1.93 kg liveweight in another in South Africa. For females the values were 18.8 g/kg liveweight at 56 d at 2.15 kg liveweight in Scotland and 15.7 g/kg liveweight at 42 d at 1.60 kg in South Africa. 2. The content of abdominal fat was, in general, increased by reducing the protein content of the diet or by dilution of the food with oil or starch. It was, in general, reduced by diluting the food with dietary fibre which also reduced liveweight gain. 3. The results are consistent with the idea that chickens attempt to control their food intake so that they achieve a particular fatness. This level of fatness differs between the sexes and between degrees of maturity.