The neurotropic virus, herpes simplex type 1 (HSV-1), inhibits the excitability of peripheral mammalian neurons, but the molecular mechanism of this effect has not been identified. Here, we use ...voltage-clamp measurement of ionic currents and an antibody against sodium channels to show that loss of excitability results from the selective, precipitous, and complete internalization of voltage-activated sodium channel proteins from the plasma membrane of neurons dissociated from rat dorsal root ganglion. The internalization process requires viral protein synthesis but not viral encapsulation, and does not alter the density of voltage-activated calcium or potassium channels. However, internalization is blocked completely when viruses lack the neurovirulence factor, infected cell protein 34.5, or when endocytosis is inhibited with bafilomycin A1 or chloroquine. Although it has been recognized for many years that viruses cause cell pathology by interfering with signal transduction pathways, this is the first example of viral pathology resulting from selective internalization of an integral membrane protein. In studying the HSV-induced redistribution of sodium channels, we have uncovered a previously unknown pathway for the rapid and dynamic control of excitability in sensory neurons by internalization of sodium channels.
Ectopic pregnancy Hebertson, R M; Storey, N D
Critical care clinics,
10/1991, Letnik:
7, Številka:
4
Journal Article
Recenzirano
The incidence of ectopic pregnancy has been increasing for many years and currently is two to three times higher than it was 20 or 25 years ago. The reasons for this are complex and include increased ...rates of pelvic and tubal infection, the use of the IUD, surgery in the pelvis for infertility, sterilization and other surgical procedures, in vitro fertilization, and improved diagnosis. Normal tubal physiology, the findings in affected tubes, and the mechanisms of how the ectopic pregnancy develops and involves the tube are considered. The cardinal points of the history and physical examination are presented in considerable detail. Further, the evolution of the tools of diagnosis--curettage, culdocentesis, laparotomy, laparoscopy, hormonal tests, and ultrasound-is considered. The different approaches to therapy are presented. Salpingectomy was once the method of accepted therapy, but currently conservative management (salpingostomy) is the most acceptable approach. More recently, selected patients are being treated with observation and a small subgroup are being managed with methotrexate and other chemical agents injected directly into the ectopic pregnancy. Ectopic pregnancy is still a leading cause of maternal death despite improved diagnosis and therapy. It should be remembered, however, that the total number of women who die from this condition is less than ever before and this is despite the rising incidence of ectopic pregnancy. There is still much to be learned about ectopic pregnancy, its etiology, diagnosis, and management.
Thirty unselected patients with chronic granulocytic leukaemia (CGL), age range 22–59 years, were treated with intensive chemotherapy and G-CSF to mobilize peripheral blood progenitor cells (PBPC). ...Chemotherapy was well tolerated and PBPC were collected by leukapheresis early during white cell recovery. PBPC collections considered adequate for engraftment were collected in 21 patients. Cytogenetic analysis of all collections in these patients showed >75% Ph negativity (range 79–100%) in 10. Successful collections, ie those >75% Ph negative and with total cell count of >1 × 106 CD34+ve cells/kg or >20 × 104 CFU-GM/kg were further analysed by Southern blot or RT-PCR. All samples were positive for the bcr/abl transcript. Patients with a low Sokal score (<0.8) were more likely to achieve a successful collection. in contrast, there was no association between transcript expression and likelihood of successful collection. we have confirmed that it is possible to mobilize and collect ph-negative enriched pbpc in unselected patients with cgl. this procedure is more likely to be successful earlier rather than later in the course of the disease. whether such collections will give an advantage over unmanipulated autologous bone marrow transplantation in cgl requires further study, but our experience suggests that suitable material for autologous rescue can be obtained from approximately one third of eligible, unselected young patients.
The use of extended local anaesthesia for postoperative pain has previously been reported, and has several advantages over other methods, including ease of placement, safety, reliability, lower cost ...and effective analgesia. We present our experience with a portable elastomeric infusion device in patients undergoing arthroscopic subacromial decompression, and make a case for its potential to allow same-day discharge.
Forty patients undergoing arthroscopic subacromial decompression were followed-up. At the end of the procedure, an epidural catheter connected to a portable elastomeric local anaesthetic infusion system was inserted into the subacromial space. All patients were electively admitted for overnight stay postoperatively and assessed using a visual analogue scale (VAS) to evaluate their level of pain.
No patient reported severe pain at any stage. None of the patients required any parenteral opiate analgesia with the pump in situ.
These findings suggest that the use of this elastomeric infusion device following shoulder surgery allows safe and early discharge of patients with decreased need for parenteral opiate analgesia.
...a considerable number of intensive care unit patients who are transferred will continue to be accompanied by inexperienced, ill equipped staff. 4 The setting up of regional dedicated transfer ...teams is urgently required to reduce the inherent risks associated with the transport of critically ill patients. 5 This should not, however, deflect attention from the need, as our figures show, for more intensive care unit beds. ...this happens, the number of transfers of critically ill patients due to the shortage of locally available beds will continue to rise.
The work described in this paper forms part of CONTESSB, a collaborative project performed by a consortium of major companies and universities in the United Kingdom. The project concerns the use of ...environmental simulation in the testing, evaluation, and validation of high-integrity systems in a range of industrial areas including the nuclear, defence, aerospace, avionics, automotive, railway, and process control industries. The paper looks at the requirements for environmental simulators for critical systems and discusses their use in demonstrating system safety. It also considers the development of the simulator and suggests methods of integrating this into the overall project development lifecycle.
Patterns of expression of surface-associated antigens were analyzed in the filarial nematode Brugia malayi immediately prior, and during development in the vertebrate host. Two surface-associated ...protein molecules, i.e., accessible to surface radioiodination and soluble in aqueous buffers, were investigated: Mrs 29-30,000 and 16,000, both of which are antigenic in infected animals. The Mr 29-30,000 glycoprotein is expressed in a surface-associated manner by adult worms and by fourth-stage larvae, but is not detectable in preparasitic third-stage larvae. The 16,000 component, which appears not to be glycosylated, is surface-associated in adult worms and fourth-stage larvae. In contrast to the 29-30,000 glycoprotein, the 16,000 protein is also expressed both by pre- and postparastic third-stage larvae. However, it becomes surface-associated only after infection. Thus, immediately prior, and during development within the vertebrate host, B. malayi displays at least two different patterns of expression of surface-associated antigens: (i) de novo, intiated either immediately after infection (phase specific) or during genesis of the fourth-stage larva (stage specific); (ii) continuous, but with phase-dependent surface exposure of previously cryptic antigens, during the transition from intermediate to definitive host.
Background: Previous studies of ion channel regulation by G proteins have focused on the larger, heterotrimeric GTPases, which are activated by heptahelical membrane receptors. In contrast, studies ...of the Rho family of smaller, monomeric, Ras-related GTPases, which are activated by cytoplasmic guanine nucleotide exchange factors, have focused on their role in cytoskeletal regulation.
Results: Here we demonstrate novel functions for the Rho family GTPases Rac and Rho in the opposing hormonal regulation of voltage-activated, ether-a-go-go-related potassium channels (ERG) in a rat pituitary cell line, GH4C1. The hypothalamic neuropeptide, thyrotropin-releasing hormone (TRH) inhibits ERG channel activity through a PKC-independent process that is blocked by RhoA(19N) and the Clostridium botulinum C3 toxin, which inhibit Rho signaling. The constitutively active, GTPase-deficient mutant of RhoA(63L) rapidly inhibits the channels when the protein is dialysed directly into the cell through the patch pipette, and inhibition persists when the protein is overexpressed. In contrast, GTPase-deficient Rac1(61L) stimulates ERG channel activity. The thyroid hormone triiodothyronine (T3), which antagonizes TRH action in the pituitary, also stimulates ERG channel activity through a rapid process that is blocked by Rac1(17N) and wortmannin but not by RhoA(19N).
Conclusions: Rho stimulation by G13-coupled receptors and Rac stimulation by nuclear hormones through PI3-kinase may be general mechanisms for regulating ion channel activity in many cell types. Disruption of these novel signaling cascades is predicted to contribute to several specific human neurological diseases, including epilepsy and deafness.
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