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At least 451 records · Page 25Linked to original sources
PubMed1998

Prenatal MRI evaluation of giant neck masses in preparation for the fetal exit procedure.

Airway compromise at birth can be anticipated with giant neck masses, so that as much anatomic information as possible is necessary prior to delivery to establish a diagnosis and assess the airway. With this study, we evaluated the usefulness of prenatal magnetic resonance imaging (MRI) for evaluation of giant fetal neck masses prior to operating on placental support, the Ex Utero Intrapartum Treatment (EXIT) procedure, performed to secure the neonatal airway. Three pregnant women with an ultrasound (US) diagnosis of fetal giant neck mass were referred for prenatal MRI. As this was our initial experience performing prenatal MRI, a variety of imaging sequences were used including spin-echo, fast gradient-echo, half-fourier single shot turbo spin-echo (Haste), and echo-planar imaging (EPI). All sequences performed were able to demonstrate the fetal airway relative to the mass. In addition, the images were able to give a more global definition of the mass because of the larger field of view than could be obtained with MRI compared to US. The Haste sequence provided the best definition of a mass because of decreased motion artifacts. The prenatal diagnosis on MRI was teratoma in two and lymphangioma in one and was confirmed at birth. MRI provided essential information about the diagnosis and the anatomy of the giant neck masses and adjacent airway in three fetuses prior to selection for the EXIT surgical procedure.

Airway Obstruction↗
PubMed1999

Transport in finite size systems: An exit time approach.

In the framework of chaotic scattering we analyze passive tracer transport in finite systems. In particular, we study models with open streamlines and a finite number of recirculation zones. In the nontrivial case with a small number of recirculation zones a description by means of asymptotic quantities (such as the eddy diffusivity) is not appropriate. The nonasymptotic properties of dispersion are characterized by means of the exit time statistics, which shows strong sensitivity on initial conditions. This yields a probability distribution function with long tails, making impossible a characterization in terms of a unique typical exit time. (c) 1999 American Institute of Physics.

Journal Article↗
PubMed2006

CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit.

In vertebrate meiosis, unfertilized eggs are arrested in metaphase II by cytostatic factor (CSF), which is required to maintain mitotic cyclin-dependent kinase activity. Fertilization triggers a transient increase in cytosolic free Ca(2+), which leads to CSF inactivation and ubiquitin-dependent cyclin destruction through the anaphase promoting complex or cyclosome (APC/C). The Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and the Polo-like kinase Plx1 are essential factors for Ca(2+)-induced meiotic exit, but the critical targets of these kinases were unknown. The APC/C inhibitor Emi2 or XErp1 has recently been characterized as a pivotal CSF component, required to maintain metaphase II arrest and rapidly destroyed in response to Ca(2+) signaling through phosphorylation by Plx1 and ubiquitination by the SCF(betaTrCP) complex. An important question is how the increase in free Ca(2+) targets Plx1 activity toward Emi2. Here, we demonstrate that CaMKII is required for Ca(2+)-induced Emi2 destruction, and that CaMKII functions as a "priming kinase," directly phosphorylating Emi2 at a specific motif to induce a strong interaction with the Polo Box domain of Plx1. We show that the strict requirement for CaMKII to phosphorylate Emi2 is a specific feature of CSF arrest, and we also use phosphatase inhibitors to demonstrate an additional mode of Emi2 inactivation independent of its destruction. We firmly establish the CSF component Emi2 as the first-known critical and direct target of CaMKII in CSF release, providing a detailed molecular mechanism explaining how CaMKII and Plx1 coordinately direct APC/C activation and meiotic exit upon fertilization.

Animals↗
PubMed2003

A discrete water exit pathway in the membrane protein cytochrome c oxidase.

By using the non-redox-active Mg2+/Mn2+ site of cytochrome c oxidase as a probe, water access from the outside of the enzyme and water escape from the buried active site were studied. Water movement was time-resolved by monitoring the magnetic interaction of the oxygen isotope 17O with the Mn2+ by using a rapid freeze-quench-electron spin echo envelope modulation technique. Rapid (msec) access of water from the bulk phase to the Mn2+ was demonstrated by mixing cytochrome c oxidase with H217O. To determine whether a channel involving the Mn2+ was used for water exit from the active site, samples incubated in 17O2 were allowed to turn over approximately five times before freezing. The 17O, now in the form of H217O, was detected at the Mn2+. The significant broadening of the Mn2+ signal after the limited number of turnovers strongly suggests that the water exits the protein by means of one discrete pathway, not by random diffusion.

Bacterial Proteins↗
PubMed1982

Nascent polypeptide chains emerge from the exit domain of the large ribosomal subunit: immune mapping of the nascent chain.

The site of the nascent polypeptide chain as it leaves the ribosome has been localized on the "exit domain" of the Escherichia coli ribosome by using IgG antibodies directed against the enzyme beta-galactosidase (EC 3.2.1.23). Thus, a functional site has been mapped on intact 70S ribosomes. The exit site is on the large subunit, approximately 70 A from the interface between subunits and nearly 150 A from the central protuberance, the likely site of peptide transfer. It is adjacent to the region corresponding to the rough endoplasmic membrane binding region of the eukaryotic ribosome but distant from ribosomal components participating in mRNA recognition and polypeptide elongation (i.e., distant from the "translational domain"). These results, together with the protease protection experiments of others, provide evidence that the nascent protein chain probably passes through the ribosome in an unfolded, fully extended conformation.

Binding Sites↗
PubMed1996

Surface antigen cross-linking triggers forced exit of a protozoan parasite from its host.

We used the common fish pathogen Ichthyophthirius multifiliis as a model for studying interactions between parasitic ciliates and their vertebrate hosts. Although highly pathogenic, Ichthyophthirius can elicit a strong protective immune response in fish after exposure to controlled infections. To investigate the mechanisms underlying host resistance, a series of passive immunization experiments were carried out using mouse monoclonal antibodies against a class of surface membrane proteins, known as immobilization antigens (or i-antigens), thought to play a role in the protective response. Such antibodies bind to cilia and immobilize I. multifiliis in vitro. Surprisingly, we found that passive antibody transfer in vivo caused rapid exit of parasites from the host. The effect was highly specific for a given I. multifiliis serotype. F(ab)2 subfragments had the same effect as intact antibody, whereas monovalent Fab fragments failed to protect. The activity of Fab could, nevertheless, be restored after subsequent i.p. injection of bivalent goat anti-mouse IgG. Parasites that exit the host had detectable antibody on their surface and appeared viable in all respects. These findings represent a novel instance among protists in which protective immunity (and evasion of the host response) result from an effect of antibody on parasite behavior.

Animals↗
PubMed1998

Endogenous E2F-1 promotes timely G0 exit of resting mouse embryo fibroblasts.

Much evidence strongly suggests a positive role for one or more E2F species in the control of exit from G0/G1. Results described here provide direct evidence that endogenous E2F-1, as predicted, contributes to progression from G0 to S. By contrast, cycling cells lacking an intact E2F-1 gene demonstrated normal cell cycle distribution. Therefore, E2F-1 exerts a unique function leading to timely G0 exit of resting cultured primary cells, while at the same time being unnecessary for normal G1 to S phase progression of cycling cells.

Animals↗
PubMed1998

Exit of major histocompatibility complex class II-invariant chain p35 complexes from the endoplasmic reticulum is modulated by phosphorylation.

The Iip35 isoform of the major histocompatibility complex (MHC) class II-associated invariant chain (Ii) contains an endoplasmic reticulum (ER) targeting motif, but in B cell lines the ER retention is ineffective and a fraction of Iip35 is transported through the Golgi complex associated with class II molecules. We found Iip35 (but not Iip33, the major form of Ii) to be phosphorylated in B cell lines, as well as in transfected HeLa cells. The phosphorylation of Iip35 was found to be necessary for the exit of Iip35-class II complexes out of the ER. This requirement suggests that phosphorylation may change the interaction with factors responsible for ER retention/retrieval, and we did find that phosphorylated Iip35 associates with 14-3-3 proteins, a family of adaptor proteins that are involved in coordinating signal transduction pathways. This finding raises the intriguing possibility that the exit of Ii-class II complexes from the ER is regulated by intracellular signaling events.

14-3-3 Proteins↗
PubMed2001

Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis.

Intraerythrocytic malaria parasites replicate by the process of schizogeny, during which time they copy their genetic material and package it into infective merozoites. These merozoites must then exit the host cell to invade new erythrocytes. To better characterize the events of merozoite escape, erythrocytes containing Plasmodium falciparum schizonts were cultured in the presence of the cysteine protease inhibitor, l-transepoxy-succinyl-leucylamido-(4-guanidino)butane (E64). This treatment resulted in the accumulation of extraerythrocytic merozoites locked within a thin, transparent membrane. Immunomicroscopy demonstrated that the single membrane surrounding the merozoites is not erythrocytic but rather is derived from the parasitophorous vacuolar membrane (PVM). Importantly, structures identical in appearance can be detected in untreated cultures at low frequency. Further studies revealed that (i) merozoites from the PVM-enclosed merozoite structures (PEMS) are invasive, viable, and capable of normal development; (ii) PEMS can be purified easily and efficiently; and (iii) when PEMS are added to uninfected red blood cells, released merozoites can establish a synchronous wave of infection. These observations suggest that l-transepoxy-succinyl-leucylamido-(4-guanidino)butane (E64) causes an accumulation of an intermediate normally present during the process of rupture. We propose a model for the process of rupture: merozoites enclosed within the PVM first exit from the host erythrocyte and then rapidly escape from the PVM by a proteolysis-dependent mechanism.

Animals↗
PubMed1998

Induced activation of the Toxoplasma gondii nucleoside triphosphate hydrolase leads to depletion of host cell ATP levels and rapid exit of intracellular parasites from infected cells.

The nucleoside triphosphate hydrolase of Toxoplasma gondii is a potent apyrase. The protein is synthesized in large amounts and transported through the secretory pathway of the parasite and into the vacuolar space in an oxidized and thereby enzymatically inactive form. Complete activation of the purified enzyme is known to require dithiols (e.g. DTT); subcellular fractionation demonstrates that little if any (<5%) of the enzyme in the vacuolar space is active in the absence of DTT. Both native and epitope-tagged nucleoside triphosphate hydrolase (NTPase) were partially activated during immunoprecipitation, precluding precise assessment of enzyme activity in the vacuolar space but suggesting that protein-protein interactions may trigger activation. When infected cells were treated with DTT, the NTPase was activated in a dose-response fashion, as assessed by migration on SDS-polyacrylamide gel electrophoresis and by an increase in enzymatic activity. After activation, enzyme activity decreased with time in the presence of DTT; this inactivation was slowed by the presence of excess ATP. A rapid fall in host cell ATP was accompanied by an abrupt exit of parasites from cells. These results demonstrate that the oxidation/reduction status of the NTPase, the only parasite dense granule protein that contains disulfide bonds, is tightly controlled within the vacuolar space and may influence parasite exit from cells.

Acid Anhydride Hydrolases↗
PubMed1999

Inactivation of p42 mitogen-activated protein kinase is required for exit from M-phase after cyclin destruction.

By using cycling Xenopus egg extracts, we have previously found that if mitogen-activated protein kinase (p42 MAPK) is activated on entry into mitosis (M-phase), the extract is arrested with condensed chromosomes and spindle microtubules. Here we show that these arrested extracts have high levels of M-phase promoting factor (MPF, Cyclin B/Cdc2) activity, stabilized levels of Cyclin B, and sustained M-phase-specific phosphorylations. We also examined the role of p42 MAPK in DNA damage checkpoint-arrested extracts that were induced to enter M-phase by the addition of Cdc25C protein. In these extracts, Cdc25C protein triggers the abrupt, premature activation of MPF and entry into M-phase. MPF activity then drops suddenly due to Cyclin B proteolysis, just as p42 MAPK is activated. Unexpectedly, however, M-phase is sustained, as judged by maintenance of M-phase-specific phosphorylations and condensed chromosomes. To determine if this M-phase arrest depended on p42 MAPK activation, we added PD98059 (PD), an inhibitor of p42 MAPK activation, to egg extracts with exogenous Cdc25. Both untreated and PD-treated extracts entered M-phase simultaneously, with a sharp peak of MPF activity. However, only PD-treated extracts subsequently exited from M-phase and entered interphase. In PD-treated extracts, p42 MAPK was not activated, and the transition to interphase was accompanied by the formation of decondensed nuclei and the disappearance of M-phase-specific phosphorylation of proteins. These results show that although entry into M-phase requires the activation of MPF, exit from M-phase even after cyclin destruction, is dependent on the inactivation of p42 MAPK.

Animals↗
PubMed2002

Control of mitotic exit in budding yeast. In vitro regulation of Tem1 GTPase by Bub2 and Bfa1.

The elimination of mitotic kinase activity at the end of mitosis is essential for progression to the next stage of the eukaryotic cell cycle. In budding yeast, this process is controlled by a regulatory cascade called the mitotic exit network. Extensive genetic data indicate that mitotic exit network activity is determined by a GTP-binding protein, Tem1, and its putative regulators, Bub2, Bfa1, and Lte1. Here we describe the purification and in vitro activities of Tem1, Bub2, and Bfa1. We describe the nucleotide binding properties of Tem1 and characterize its intrinsic GTPase activity. The combination of Bfa1 and Bub2 acts as a two-component GTPase-activating protein for Tem1. In the absence of Bub2, Bfa1 inhibits the GTPase and GTP exchange activities of Tem1. This inhibition is elicited by either the N- or C-terminal regions of Bfa1, which also retain some ability to co-activate GTPase activity in the presence of Bub2. Although the C-terminal region of Bfa1 binds to Bub2, no interaction of the N-terminal half of Bfa1 with Bub2 was detected despite their combined GAP activity. Therefore, we propose that Bfa1 acts both as an adaptor to connect Bub2 and Tem1 and as an allosteric effector that facilitates this interaction.

Cell Cycle Proteins↗
PubMed2003

Apolipoprotein B100 exit from the endoplasmic reticulum (ER) is COPII-dependent, and its lipidation to very low density lipoprotein occurs post-ER.

Hepatic apolipoprotein B100 (apoB100) associates with lipids to form dense lipoprotein particles in the endoplasmic reticulum (ER) and is further lipidated to very low density lipoproteins (VLDL). Because the VLDL diameter can exceed 200 nm, classical ER-derived vesicles may be unable to accommodate VLDLs. Using hepatic membranes and cytosol to reconstitute ER budding, apoB100-containing vesicles sedimented distinct from those harboring more typical cargo but contained Sec23. Moreover, ER exit of apoB was inhibited by dominant-negative Sar1. Budding required Sar1 regardless of whether oleic acid (OA) was added to stimulate apoB lipidation; therefore, either large apoB100-lipoproteins reside in secretory vesicles, or full lipidation occurs post-ER. Using membranes from cells incubated in the presence or absence of OA, we determined that apoB100-lipoproteins in ER vesicles had not become lipidated to VLDLs. VLDL particles resided in the Golgi, but not the ER, after fractionation of OA-treated cells. We conclude that apoB100-lipoproteins exit the ER in COPII vesicles, but under conditions favorable for VLDL formation final lipid loading occurs post-ER.

Animals↗
PubMed2006

BM88 is a dual function molecule inducing cell cycle exit and neuronal differentiation of neuroblastoma cells via cyclin D1 down-regulation and retinoblastoma protein hypophosphorylation.

Control of cell cycle progression/exit and differentiation of neuronal precursors is of paramount importance during brain development. BM88 is a neuronal protein associated with terminal neuron-generating divisions in vivo and is implicated in mechanisms underlying neuronal differentiation. Here we have used mouse neuroblastoma Neuro 2a cells as an in vitro model of neuronal differentiation to dissect the functional properties of BM88 by implementing gain- and loss-of-function approaches. We demonstrate that stably transfected cells overexpressing BM88 acquire a neuronal phenotype in the absence of external stimuli, as judged by enhanced expression of neuronal markers and neurite outgrowth-inducing signaling molecules. In addition, cell cycle measurements involving cell growth assays, BrdUrd incorporation, and fluorescence-activated cell sorting analysis revealed that the BM88-transfected cells have a prolonged G(1) phase, most probably corresponding to cell cycle exit at the G(0) restriction point, as compared with controls. BM88 overexpression also results in increased levels of the cell cycle regulatory protein p53, and accumulation of the hypophosphorylated form of the retinoblastoma protein leading to cell cycle arrest, with concomitant decreased levels and, in many cells, cytoplasmic localization of cyclin D1. Conversely, BM88 gene silencing using RNA interference experiments resulted in acceleration of cell proliferation accompanied by impairment of retinoic acid-induced neuronal differentiation of Neuro 2a cells. Taken together, our results suggest that BM88 plays an essential role in regulating cell cycle exit and differentiation of Neuro 2a cells toward a neuronal phenotype and further support its involvement in the proliferation/differentiation transition of neural stem/progenitor cells during embryonic development.

Animals↗
PubMed2007

Association of protein biogenesis factors at the yeast ribosomal tunnel exit is affected by the translational status and nascent polypeptide sequence.

Ribosome-associated protein biogenesis factors (RPBs) act during a short but critical period of protein biogenesis. The action of RPBs starts as soon as a nascent polypeptide becomes accessible from the outside of the ribosome and ends upon termination of translation. In yeast, RPBs include the chaperones Ssb1/2 and ribosome-associated complex, signal recognition particle, nascent polypeptide-associated complex (NAC), the aminopeptidases Map1 and Map2, and the Nalpha-terminal acetyltransferase NatA. Here, we provide the first comprehensive analysis of RPB binding at the yeast ribosomal tunnel exit as a function of translational status and polypeptide sequence. We measured the ratios of RPBs to ribosomes in yeast cells and determined RPB occupation of translating and non-translating ribosomes. The combined results imply a requirement for dynamic and coordinated interactions at the tunnel exit. Exclusively, NAC was associated with the majority of ribosomes regardless of their translational status. All other RPBs occupied only ribosomal subpopulations, binding with increased apparent affinity to randomly translating ribosomes as compared with non-translating ones. Analysis of RPB interaction with homogenous ribosome populations engaged in the translation of specific nascent polypeptides revealed that the affinities of Ssb1/2, NAC, and, as expected, signal recognition particle, were influenced by the amino acid sequence of the nascent polypeptide. Complementary cross-linking data suggest that not only affinity of RPBs to the ribosome but also positioning can be influenced in a nascent polypeptide-dependent manner.

Cross-Linking Reagents↗
PubMed1996

The Coma Exit Chart: assessing the patient in prolonged coma and the vegetative state.

The patient who remains in prolonged coma or in the vegetative state presents major problems in medicine, ethics and resource economics. Diagnosis and decision making are often difficult. A Coma Exit Chart can be developed using the parameters of the Glasgow Coma Scale to measure the exiting of the patient from prolonged coma or the vegetative state.

Awareness↗
PubMedDate not supplied

Evidence-based programs for the prevention of early exit from work.

Aging of the population and lowered average age of retirement imply greatly increased public costs for pensions and health care in western societies. Prolongation of working life is necessary to counteract large budget deficits, and most western countries are now in the process of changing public retirement benefits. However, a prolongation must be accomplished without threatening the well-being of elderly persons, and therefore working life needs changes that accommodate the capacity and demands of an aging work force are needed. No scientific intervention studies have as yet demonstrated that early exits from working life can be prevented while work ability, health, productivity, and a high quality of life are maintained. However, several studies on return-to-work after prolonged sick leave, re-entry to work after lay-offs, risk factors for early retirement, risk/health factors for maintained work ability, and case studies provide indirect support for the feasibility of preventing early exits, Scientific studies comparing different approaches, and performed in varying cultural and environmental conditions, are needed.

Evidence-Based Medicine↗
PubMed2002

Bereavement support for couples following death of a baby: program development and 14-year exit analysis.

Program development, implementation, and a 14-year exit analysis of a bereavement support program for couples whose baby died in the Neonatal Intensive Care Unit (NICU) is presented. A closed, hospital-based, time-limited (12 weeks) format was used. Team leadership was used and 54% of bereaved NICU parents participated. Each group was structured with a 2-week introductory period, open format grief-focused weekly discussions,evaluation in Week 11, and summary session with termination in Week 12. The exit analysis details program strengths, weaknesses, and recommendations. Bereavement support groups are one part of what we contend should be a comprehensive bereavement program,organized to care for families prior to, during, and after a baby's death. A sensitive, spiritually aware, supportive environment should be maintained throughout with relationship building as a cornerstone of the program.

Bereavement↗