Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EXIT”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 181 records · Page 10Linked to original sources
PubMed1990

A review of Staphylococcus aureus exit-site and tunnel infections in peritoneal dialysis patients.

Staphylococcus aureus peritoneal exit-site and tunnel infections are a source of considerable morbidity for peritoneal dialysis patients. These infections are difficult to resolve, can lead to peritonitis, and often require removal of the peritoneal catheter. Staphylococcal nasal carriage is the major risk factor for S aureus exit-site infections and peritonitis episodes. In the future, the identification of patients who are S aureus nasal carriers and then treatment of the carriage state with rifampin may prove to be a means of decreasing infection rates. The best treatment for S aureus exit-site and tunnel infections has not been established. Treatment regimens in general use include oral antibiotics or intraperitoneal vancomycin. The optimal length of therapy is also unclear. Since the development of the disconnect peritoneal dialysis system, S aureus, rather than the Staphylococcus epidermidis, is the leading cause of peritonitis. To further decrease peritonitis rates, attention must now be directed at catheter-related peritonitis episodes, with S aureus the most common cause of such episodes. Controlled, prospective studies designed to investigate methods of preventing and treating S aureus exit-site infections in peritoneal dialysis patients are needed.

Anti-Bacterial Agents↗
PubMed1990

Toxic shock syndrome with Staphylococcus aureus exit-site infection in a patient on peritoneal dialysis.

Toxic shock syndrome (TSS) associated with exit-site infection but without peritonitis has not been described. We report a case of TSS with an isolated Staphylococcus aureus exit-site infection in a boy on chronic peritoneal dialysis. The exit site had minimal erythema and no purulence. This report re-emphasizes the fact that mildly appearing cutaneous infections in patients with chronic renal failure may have significant consequences. Particular attention should be given to patients who present with constitutional symptoms that may be of short duration. The importance of culturing all sites in such cases is highlighted. The prevalence of TSS with exit-site infections is unknown, but TSS should be considered in patients presenting with similar features.

Adolescent↗
PubMed1996

A randomized trial of Staphylococcus aureus prophylaxis in peritoneal dialysis patients: mupirocin calcium ointment 2% applied to the exit site versus cyclic oral rifampin.

The objective of this study was to compare prophylaxis for Staphylococcus aureus infections in peritoneal dialysis patients using 600 mg cyclic oral rifampin for 5 days every 3 months versus mupirocin calcium ointment 2% applied daily to the exit site. The study design was a prospective randomized trial, controlling for S aureus nasal carriage. Eighty-two continuous ambulatory and continuous cyclic peritoneal dialysis patients (54% male, 71 % white, 34% insulin-dependent, mean prestudy time on peritoneal dialysis 1.2 years) were randomly assigned to cyclic rifampin (n = 41 patients) or daily exit site mupirocin prophylaxis (n = 41 patients). Mean follow-up was 1 year. S aureus catheter infection rates were 0.13/yr with mupirocin and 0.15/yr with rifampin (P = NS). Both rates were significantly lower than the center's historical rate (the period between 1983 and 1992) of 0.46/yr prior to the study (P < 0.001). S aureus peritonitis rates were 0.04/yr with mupirocin and 0.02/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.16/yr (P < 0.02). Catheter loss due to S aureus infections was 0.02/yr with mupirocin and 0/yr with rifampin (P = NS), both significantly lower than the center's historical rate of 0.12/yr (P < 0.001). There were no side effects in patients using mupirocin, but 12% were unable to continue rifampin due to side effects. We conclude that mupirocin ointment at the exit site and cyclic oral rifampin are equally effective in reducing S aureus catheter infections. In addition, rifampin or mupirocin significantly reduced S aureus peritonitis and catheter loss due to S aureus infections. Mupirocin at the exit site provides an excellent alternative prophylaxis for S aureus infections, particularly in patients who cannot tolerate oral rifampin therapy.

Administration, Cutaneous↗
PubMed1996

Peritonitis associated with exit site and tunnel infections.

We reviewed all episodes of peritonitis associated with exit site and/or tunnel infection (n = 87; rate, 0.1/yr; 13% of all peritonitis episodes) occurring from 1979 to 1995. The exit site or tunnel infection was diagnosed at the time or shortly after the patient presented with peritonitis in 66% of the episodes. In the other one third the exit site or tunnel infection was diagnosed a median of 40 days prior to the development of peritonitis. Staphylococcus aureus accounted for 52% of episodes. Pseudomonas aeruginosa was the next most common organism. In 63 (72%) of the episodes the catheter was removed to resolve the infection at a median of 8 days (range, 0 to 226 days) from the onset of peritonitis. Catheter removal after 5 days predominately for refractory peritonitis (n = 23; median time to removal, 8 days) or relapsing peritonitis (n = 11; median time to catheter removal, 103 days). Patients with relapsing peritonitis suffered two to four episodes prior to removal of the catheter. Patients with peritonitis associated with tunnel infection were more likely to lose their catheter than patients with peritonitis associated with exit site infection (86% v 58%), while Staphylococcus epidermidis infections were less likely to result in catheter loss compared with all other organisms (15% v 82%). After a protocol to reduce S aureus catheter infections was implemented in 1990, the rate of catheter-related peritonitis decreased from 0.14/yr to 0.05/yr due to a decrease in S aureus episodes. We conclude that peritonitis episodes associated with a tunnel infection infrequently resolve without catheter removal. Delayed catheter removal in such circumstances often results in refractory or relapsing peritonitis. Therefore, catheter removal should be done promptly. Antibiotic prophylaxis for S aureus can reduce catheter-related peritonitis.

Bacterial Infections↗
PubMed2000

The Bfa1/Bub2 GAP complex comprises a universal checkpoint required to prevent mitotic exit.

At the end of the cell cycle, cyclin-dependent kinase (CDK) activity is inactivated to allow mitotic exit [1]. A protein phosphatase, Cdc14, plays a key role during mitotic exit in budding yeast by activating the Cdh1 component of the anaphase-promoting complex to degrade cyclin B (Clb) and inducing the CDK inhibitor Sic1 to inactivate Cdk1 [2]. To prevent mitotic exit when the cell cycle is arrested at G2/M, cells must prevent CDK inactivation. In the spindle checkpoint pathway, this is accomplished through Bfa1/Bub2, a heteromeric GTPase-activating protein (GAP) that inhibits Clb degradation by keeping the G protein Tem1 inactive [3-5]. Tem1 is required for Cdc14 activation. Here we show that in budding yeast, BUB2 and BFA1 are also required for the maintenance of G2/M arrest in response to DNA damage and to spindle misorientation. cdc13-1 bub2 and cdc13-1 bfa1 but not cdc13-1 mad2 double mutants rebud and reduplicate their DNA at the restrictive temperature. We also found that the delay in mitotic exit in mutants with misoriented spindles depended on BUB2 and BFA1, but not on MAD2. We propose that Bfa1/Bub2 checkpoint pathway functions as a universal checkpoint in G2/M that prevents CDK inactivation in response to cell-cycle delay in G2/M.

Actins↗
PubMed2001

The cyclin-dependent kinase inhibitor Roughex is involved in mitotic exit in Drosophila.

BACKGROUND: Exit from mitosis is a tightly regulated event. This process has been studied in greatest detail in budding yeast, where several activities have been identified that cooperate to downregulate activity of the cyclin-dependent kinase (CDK) Cdc28 and force an exit from mitosis. Cdc28 is inactivated through proteolysis of B-type cyclins by the multisubunit ubiquitin ligase termed the anaphase promoting complex/cyclosome (APC/C) and inhibition by the cyclin-dependent kinase inhibitor (CKI) Sic1. In contrast, the only mechanism known to be essential for CDK inactivation during mitosis in higher eukaryotes is cyclin destruction. RESULTS: We now present evidence that the Drosophila CKI Roughex (Rux) contributes to exit from mitosis. Observations of fixed and living embryos show that metaphase is significantly longer in rux mutants than in wild-type embryos. In addition, Rux overexpression is sufficient to drive cells experimentally arrested in metaphase into interphase. Furthermore, rux mutant embryos are impaired in their ability to overcome a transient metaphase arrest induced by expression of a stable cyclin A. Rux has numerous functional similarities with Sic1. While these proteins share no sequence similarity, we show that Sic1 inhibits mitotic Cdk1-cyclin complexes from Drosophila in vitro and in vivo. CONCLUSIONS: Rux inhibits Cdk1-cyclin A kinase activity during metaphase, thereby contributing to exit from mitosis. To our knowledge, this is the first mitotic function ascribed to a CKI in a multicellular organism and indicates the existence of a novel regulatory mechanism for the metaphase to anaphase transition during development.

Animals↗
PubMed2001

Asymmetric spindle pole localization of yeast Cdc15 kinase links mitotic exit and cytokinesis.

The inactivation of mitotic cyclin-dependent kinases (CDKs) during anaphase is a prerequisite for the completion of nuclear division and the onset of cytokinesis [1, 2]. In the budding yeast Saccharomyces cerevisiae, the essential protein kinase Cdc15 [3] together with other proteins of the mitotic exit network (Tem1, Lte1, Cdc5, and Dbf2/Dbf20 [4-7]) activates Cdc14 phosphatase, which triggers cyclin degradation and the accumulation of the CDK inhibitor Sic1 [8]. However, it is still unclear how CDK inactivation promotes cytokinesis. Here, we analyze the properties of Cdc15 kinase during mitotic exit. We found that Cdc15 localized to the spindle pole body (SPB) in a unique pattern. Cdc15 was present at the SPB of the mother cell until late mitosis, when it also associated with the daughter pole. High CDK activity inhibited this association, while dephosphorylation of Cdc15 by Cdc14 phosphatase enabled it. The analysis of Cdc15 derivatives indicated that SPB localization was specifically required for cytokinesis but not for mitotic exit. These results show that Cdc15 has two separate functions during the cell cycle. First, it is required for the activation of Cdc14. CD14, in turn, promotes CDK inactivation and also dephosphorylates of Cdc15. As a consequence, Cdc15 binds to the daughter pole and triggers cytokinesis. Thus, Cdc15 helps to coordinate mitotic exit and cytokinesis.

Cell Cycle Proteins↗
PubMed2003

Septins have a dual role in controlling mitotic exit in budding yeast.

In Saccharomyces cerevisiae, the spindle position checkpoint ensures that cells do not exit mitosis until the mitotic spindle moves into the mother/bud neck and thus guarantees that each cell receives one nucleus [1-6]. Mitotic exit is controlled by the small G protein Tem1p. Tem1p and its GTPase activating protein (GAP) Bub2p/Bfa1p are located on the daughter-bound spindle pole body. The GEF Lte1p is located in the bud. This segregation helps keep Tem1p in its inactive GDP state until the spindle enters the neck. However, the checkpoint functions without Lte1p and apparently senses cytoplasmic microtubules in the mother/bud neck [7-9]. To investigate this mechanism, we examined mutants defective for septins, which compose a ring at the neck [10]. We found that the septin mutants sep7Delta and cdc10Delta are defective in the checkpoint. When movement of the spindle into the neck was delayed, mitotic exit occurred, inappropriately leaving both nuclei in the mother. In sep7Delta and cdc10Delta mutants, Lte1p is mislocalized to the mother. In sep7Delta, but not cdc10Delta, mutants, inappropriate mitotic exit depends on Lte1p. These results suggest that septins serve as a diffusion barrier for Lte1p, and that Cdc10p is needed for the septin ring to serve as a scaffold for a putative microtubule sensor.

Cell Cycle Proteins↗
PubMed2003

Grazing exit electron probe microanalysis of submicrometer inclusions in metallic materials.

Grazing exit electron probe microanalysis (GE-EPMA) is a new method of EPMA in which characteristic X-rays emitted from only near-surface regions of a specimen are detected at extremely low exit angles near 0 degrees (the grazing exit condition). This technique requires the analytical objects exist on a flat surface. Therefore, the GE-EPMA analysis has been used only for the analysis of particles or a thin film on a flat substrate so that there were only few applications for practical analysis. As a new application, we have carried out GE-EPMA analysis of approximately 0.2-microm inclusions on stainless steel, which appeared to be a projection on the specimen surface with chemical etching. The GE-EPMA quantitative results were in excellent agreement with those of inclusions that were extracted from the stainless steel and analyzed by EPMA with conventional exit condition (30 degrees). This method could be, therefore, applied to the analysis of the submicrometer inclusion in a wide variety of metallic materials if the inclusion appears to be a projection with chemical etching treatment.

Journal Article↗
PubMed2002

APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit.

Cyclin degradation is central to regulation of the cell cycle. Mitotic exit was proposed to require degradation of the S phase cyclin Clb5 by the anaphase-promoting complex activated by Cdc20 (APC(Cdc20)). Furthermore, Clb5 degradation was thought to be necessary for effective dephosphorylation and activation of the APC regulatory subunit Cdh1 (also known as Hct1) and the cyclin-dependent kinase inhibitor Sic1 by the phosphatase Cdc14, allowing mitotic kinase inactivation and mitotic exit. Here we show, however, that spindle disassembly and cell division occur without significant APC(Cdc20)-mediated Clb5 degradation, as well as in the absence of both Cdh1 and Sic1. We find instead that destruction-box-dependent degradation of the mitotic cyclin Clb2 is essential for mitotic exit. APC(Cdc20) may be required for an essential early phase of Clb2 degradation, and this phase may be sufficient for most aspects of mitotic exit. Cdh1 and Sic1 may be required for further inactivation of Clb2-Cdk1, regulating cell size and the length of G1.

Amino Acid Motifs↗
PubMed2006

The reversibility of mitotic exit in vertebrate cells.

A guiding hypothesis for cell-cycle regulation asserts that regulated proteolysis constrains the directionality of certain cell-cycle transitions. Here we test this hypothesis for mitotic exit, which is regulated by degradation of the cyclin-dependent kinase 1 (Cdk1) activator, cyclin B. Application of chemical Cdk1 inhibitors to cells in mitosis induces cytokinesis and other normal aspects of mitotic exit, including cyclin B degradation. However, chromatid segregation fails, resulting in entrapment of chromatin in the midbody. If cyclin B degradation is blocked with a proteasome inhibitor or by expression of non-degradable cyclin B, Cdk inhibitors will nonetheless induce mitotic exit and cytokinesis. However, if after mitotic exit, the Cdk1 inhibitor is washed free from cells in which cyclin B degradation is blocked, the cells can revert back to M phase. This reversal is characterized by chromosome recondensation, nuclear envelope breakdown, assembly of microtubules into a mitotic spindle, and in most cases, dissolution of the midbody, reopening of the cleavage furrow, and realignment of chromosomes at the metaphase plate. These findings demonstrate that proteasome-dependent degradation of cyclin B provides directionality for the M phase to G1 transition.

Animals↗
PubMed2003

A non-proteolytic function of separase links the onset of anaphase to mitotic exit.

Separase is a protease that triggers chromosome segregation at anaphase onset by cleaving cohesin, the chromosomal protein complex responsible for sister chromatid cohesion. After anaphase, cells exit from mitosis; that is, they complete downregulation of cyclin-dependent kinase activity, undergo cytokinesis and enter G1 of the next cell cycle. Here we show that separase activation at the onset of anaphase is sufficient to promote release from the nucleolus and activation of the budding yeast phosphatase, Cdc14, a key step in mitotic exit. The ability of separase to activate Cdc14 is independent of its protease function but may involve promoting phosphorylation of the Cdc14 inhibitor Net1. This novel separase function is coregulated with its proteolytic activity by the separase inhibitor securin. This helps to explain the coupling of anaphase and mitotic exit--after securin degradation at anaphase onset, separase cleaves cohesin to trigger chromosome segregation and concurrently uses a non-proteolytic mechanism to initiate mitotic exit.

Anaphase↗
PubMed2005

Shh directs cell-cycle exit by activating p57Kip2 in the zebrafish retina.

The Hedgehog (Hh) family of signalling proteins control both differentiation and proliferation during animal development. Previous studies have shown that Hh signalling has a stimulatory effect on the cell cycle in several organs by controlling core cell-cycle components. Here, we show that Sonic hedgehog (Shh) signalling has the opposite effect in the zebrafish retina, where it leads to cell-cycle exit, and that this is mediated by transcriptional activation of the cyclin kinase inhibitor p57Kip2. The loss of p57Kip2 activity strongly resembles the Shh mutant eye phenotype, and overexpression of p57Kip2 rescues cell-cycle exit in Shh mutants, indicating that p57Kip2 is both necessary and sufficient to mediate Shh-induced cell-cycle exit in the retina. These findings raise the possibility that stimulation of cell-cycle exit through regulation of core cell-cycle components may be part of a general mechanism required for Hh-directed differentiation.

Animals↗
PubMed1980

Quantitative analysis of proton-linked transport system. beta-Galactoside exit in Escherichia coli.

The exit of lactose and thiomethyl-beta-D-galactoside from Escherichia coli ML308-225 has been studied to determine the role of carrier-dependent (zero-trans efflux) and carrier-independent (leak) processes. On the basis of its sensitivity to p-chloromercuribenzene sulphonate the exit of lactose was found to be almost wholly mediated by the carrier. Consistent with this conclusion was the finding that the rate of exit of this sugar was dependent on the external pH, being considerably slower at acid pH. On the other hand exit of thiomethyl-beta-D-galactoside was found to be composed of both carrier-dependent and carrier-independent processes. Both processes exhibited first-order kinetics with the rate constants for zero-trans efflux and leak being 0.137 min-1 and 0.079 min-1, respectively. The relevance of these findings for out earlier proposal for the methods of attenuation of solute accumulation is discussed [Booth, Mitchell & Hamilton (1979) Biochem. J. 182, 687--696].

4-Chloromercuribenzenesulfonate↗
PubMed2000

A jump in cycle length of orthodromic common atrial flutter during catheter ablation at the isthmus between the inferior vena cava and tricuspid annulus; evidence of dual isthmus conduction directed to dual septal exits.

INTRODUCTION: In orthodromic common atrial flutter (AFL), details of intraseptal propagation of the flutter (FL) wave exiting from the isthmus between the inferior vena cava and tricuspid annulus (IVC-TA isthmus) remain unknown. We hypothesized the existence of dual septal exits of the FL wave from the IVC-TA isthmus to both the anterior, coronary sinus ostium (CSO-TA) isthmus, and the posterior septal (IVC-CSO) isthmus, and that the IVC-TA isthmus might consist of dual muscle bundles directed to both septal isthmuses over the eustachian ridge; therefore, segmental ablation of the IVC-TA isthmus could change intraseptal FL wave propagation. METHODS AND RESULTS: To test the hypothesis, we investigated the influence of segmental ablation of the IVC-TA isthmus on intraseptal FL wave propagation. In seven of 40 (18%) consecutive patients, segmental ablation of the ventricular side of the IVC-TA isthmus during orthodromic common AFL led to sudden prolongation of the flutter cycle length (FCL) (from 266 +/- 33 ms to 291 +/- 45 ms) associated with changes in intraseptal activation sequences. They consisted of prolongation of the interval between the IVC-TA isthmus and the CSO (from 38 +/- 13 ms to 86 +/- 25 ms), shortening of the interval between the CSO and His (from 31 +/- 15 ms to 9 +/- 15 ms), and atrial electrogram polarity change at the His-bundle recording site. Morphological change in the FL wave was also seen on the 12-lead ECG. CONCLUSIONS: In some patients, segmental ablation of the IVC-TA isthmus can lead to a jump in FCL and changes in intraseptal activation sequences of FL waves due to anterior-to-posterior shifting of the septal exit. This indicates that the IVC-TA isthmus may contain dual circumferential muscle bundles as conduction pathways directed to dual septal exits both anterior and posterior to the CSO.

Atrial Flutter↗
PubMed2004

Regulation of cyclin-dependent kinase activity during mitotic exit and maintenance of genome stability by p21, p27, and p107.

To study the regulation of cyclin-dependent kinase (CDK) activity during mitotic exit in mammalian cells, we constructed murine cell lines that constitutively express a stabilized mutant of cyclin A (cyclin A47). Even though cyclin A47 was expressed throughout mitosis and in G1 cells, its associated CDK activity was inactivated after the transition from metaphase to anaphase. Cyclin A47 associated with both p21 and p27 during mitotic exit, implicating these proteins in CDK inactivation. However, cyclin A47 was fully inhibited during the M-to-G1 transition in p21(-/-) p27(-/-) fibroblasts. Also, the CDKs associated with cyclin A47 were not inactivated by phosphorylation at tyrosines. The protein responsible for CDK inactivation during mitotic exit in p21/p27 null cells was the Rb family member, p107. p107 bound to cyclin A47 when p21 and p27 were absent, and cyclin A47-CDK activity was not inactivated during the M-to-G1 transition in p21(-/-) p27(-/-) p107(-/-) null fibroblasts. Enforced expression of cyclin A in cells lacking all three CDK inhibitors induced rapid tetraploidization, indicative of mitotic failure/endoreduplication. We concluded that cyclin proteolysis and CDK inhibitors constitute redundant pathways that control cyclin A-CDK activity during mitotic exit in mammalian cells and that loss of these pathways can cause genetic instability.

3T3 Cells↗
PubMed2002

Bfa1 can regulate Tem1 function independently of Bub2 in the mitotic exit network of Saccharomyces cerevisiae.

In budding yeast, exit from mitosis is achieved by inactivation of Cdc28/Clb2 activity. Although it is not clear at present how mitotic exit is triggered, a growing body of evidence suggests that the Tem1 GTPase plays a critical role in mediating this pathway and that Bfa1 and Bub2 constitute a two-component GTPase-activating protein to negatively regulate Tem1. Here, we have demonstrated that introduction of bfa1 Delta suppresses the growth defects associated with the cdc5-1 mutation significantly better than that of bub2 Delta, suggesting that Bfa1 may have a previously uncharacterized role in this pathway. Overexpression of BFA1 efficiently arrested the cell cycle at postanaphase even in the absence of BUB2, whereas overexpression of BUB2 weakly induced mitotic arrest only in the presence of BFA1. Coimmunoprecipitation and in vitro binding studies indicate that Bfa1 binds strongly to Tem1 independently of Bub2. Provision of GDP+AlF(4)(-), which mimics the GTPase transition state, enhanced the Bub2-Tem1 interaction both in vitro and in vivo. Interestingly, introduction of bfa1 Delta, but not bub2 Delta, greatly increased the interaction between Tem1 and Cdc15, a step that is thought to be critical for activating the mitotic exit network. Our data suggest that, in addition to its role as a putative, two-component GTPase-activating protein with Bub2, Bfa1 also can play a role in the regulation of mitotic exit by directly inhibiting the interaction between Tem1 and Cdc15 even in the absence of Bub2.

Cell Cycle Proteins↗
PubMed1998

The von Hippel-Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal.

The inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene predisposes affected individuals to the human VHL cancer syndrome and is associated with sporadic renal cell carcinomas (RCC) and brain hemangioblastomas. VHL-negative 786-0 RCC cells are tumorigenic in nude mice which is suppressed by the reintroduction of VHL. Remarkably, this occurs without affecting the growth rate and cell cycle profile of these cells in culture. The 786-0 cell line, like many cancer cells, fails to exit the cell cycle upon serum withdrawal. Here, it is shown that reintroduction of the wild-type VHL gene restores the ability of VHL-negative RCC cancer cells to exit the cell cycle and enter G0/quiescence in low serum. Both VHL-positive and VHL-negative RCC cells exit the cell cycle by contact inhibition. The cyclin-dependent kinase inhibitor, p27, accumulates upon serum withdrawal, only in the presence of VHL, as a result of the stabilization of the protein. We propose that the loss of wild-type VHL gene results in a specific cellular defect in serum-dependent growth control, which may initiate tumor formation. This is corrected by the reintroduction of wild-type VHL, implicating VHL as the first tumor suppressor involved in the regulation of cell cycle exit, which is consistent with its gatekeeper function in the kidney.

Animals↗