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At least 487 records · Page 27Linked to original sources
PubMed2006

Ochratoxin A: apoptosis and aberrant exit from mitosis due to perturbation of microtubule dynamics?

Ochratoxin A (OTA) is a potent nephrotoxin and causes high incidences of renal tumors in rodents. The molecular events leading to tumor formation by OTA are not well defined. Early pathological changes observed in kidneys of rats treated with OTA in vivo include frequent mitotic and abnormally enlarged cells, detachment of tubule cells, and apoptosis within the S3 segment of the proximal tubule, suggesting that OTA may interfere with molecules involved in the regulation of cell division and apoptosis. In this study, treatment of immortalized human kidney epithelial (IHKE) cells with OTA (0-50 microM) resulted in a time- and dose-dependent increase in apoptosis and activation of c-Jun N-terminal kinase. At the same time, OTA blocked metaphase/anaphase transition and led to the formation of aberrant mitotic figures and giant cells with abnormally enlarged and/or multiple nuclei, sometimes still connected by chromatin bridges. Immunostaining of the mitotic apparatus using an alpha-tubulin antibody revealed defects in spindle formation. In addition, OTA inhibited microtubule assembly in a concentration-dependent manner in a cell-free, in vitro assay. Interestingly, treatment with OTA also resulted in activation of the transcription factor nuclear factor kappa B (NFkappaB), which has recently been shown to promote cell survival during mitotic cell cycle arrest. Based on these observations, we hypothesize that the mechanism by which OTA promotes tumor formation involves interference with microtubuli dynamics and mitotic spindle formation, resulting in apoptosis or-in the presence of survival signals such as stimulation of the NFkappaB pathway-premature exit from mitosis. Aberrant exit from mitosis resulting in blocked or asymmetric cell division may favor the occurrence of cytogenetic abnormalities and may therefore play a critical role in renal tumor formation by OTA.

Apoptosis↗
PubMed1999

Entrance, exit, and reentrance of one shot with a shotgun.

The case being reported is one of a homicidal shotgun fatality with an unusual wound pattern. A 34-year-old man was shot at close range with a 12-gauge shotgun armed with No. 5 birdshot ammunition. The shot entered the left axillary region, exited through the left infraclavicular region, and thereafter penetrated the left side of the neck, causing tearing of the left common carotid artery and the right internal carotid artery. The entrance wound in the axilla was larger than the other wounds, and before autopsy it was believed that the shotgun had been fired twice, causing one wound in the neck and one wound perforating the infraclavicular region and exiting through the left axillary region. Thus, this case shows that unusual wound patterns in shotgun fatalities can easily lead to incorrect assumptions with regard to number and direction of shots fired unless thorough investigation is carried out postmortem.

Adult↗
PubMed1999

Pds1p of budding yeast has dual roles: inhibition of anaphase initiation and regulation of mitotic exit.

Progression through mitosis is controlled by protein degradation that is mediated by the anaphase-promoting complex/cyclosome (APC/C) and its associated specificity factors. In budding yeast, APC/C(Cdc20) promotes the degradation of the Pds1p anaphase inhibitor at the metaphase-to-anaphase transition, whereas APC/C(Cdh1) promotes the degradation of the mitotic cyclins at the exit from mitosis. Here we show that Pds1p has a novel activity as an inhibitor of mitotic cyclin destruction, apparently by preventing the activation of APC/C(Cdh1). This activity of Pds1p is independent of its activity as an anaphase inhibitor. We propose that the dual role of Pds1p as an inhibitor of anaphase and of cyclin degradation allows the cell to couple the exit from mitosis to the prior completion of anaphase. Finally, these observations provide a novel regulatory paradigm in which the sequential degradation of two substrates is determined by the substrates themselves, such that an early substrate inhibits the degradation of a later one.

Anaphase↗
PubMed1999

Exit time of turbulent signals: a way to detect the intermediate dissipative range.

The exit-time statistics of experimental turbulent data is analyzed. By looking at the exit-time moments (inverse structure functions) it is possible to have a direct measurement of scaling properties of the laminar statistics. It turns out that the inverse structure functions show a much more extended intermediate dissipative range than the structure functions, leading to the first clear evidence of the existence of such a range of scales.

Journal Article↗
PubMed2003

Limit of small exits in open Hamiltonian systems.

The nature of open Hamiltonian systems is analyzed, when the size of the exits decreases and tends to zero. Fractal basins appear typically in open Hamiltonian systems, but we claim that in the limit of small exits, the invariant sets tend to fill up the whole phase space with the strong consequence that a new kind of basin appears, where the unpredictability grows indefinitely. This means that for finite, arbitrarily small accuracy, we can find uncertain basins, where any information about the future of the system is lost. This total indeterminism had only been reported in dissipative systems, in particular in the so-called intermingled riddled basins, as well as in the riddledlike basins. We show that this peculiar, behavior is a general feature of open Hamiltonian systems.

Journal Article↗
PubMed2005

Resonant exit time in stochastic and deterministic systems.

The motion of a particle in the field of a time-dependent potential is studied here both at absolute zero and in the presence of thermal agitation. The potential executes either random fluctuations or deterministic harmonic oscillations. Assuming absorbing boundaries it is always possible to find an exit time tau(ex)(kappa) which has a local minimum as a function of the potential flip rate kappa. Thus resonant activation, usually associated with diffussive systems, exists in purely deterministic systems as well. Thermal agitation merely extends the range of admissible initial conditions and renders all exit times finite.

Journal Article↗
PubMed2005

Scaling and data collapse for the mean exit time of asset prices.

We study theoretical and empirical aspects of the mean exit time (MET) of financial time series. The theoretical modeling is done within the framework of continuous time random walk. We empirically verify that the mean exit time follows a quadratic scaling law and it has associated a prefactor which is specific to the analyzed stock. We perform a series of statistical tests to determine which kind of correlation are responsible for this specificity. The main contribution is associated with the autocorrelation property of stock returns. We introduce and solve analytically both two-state and three-state Markov chain models. The analytical results obtained with the two-state Markov chain model allows us to obtain a data collapse of the 20 measured MET profiles in a single master curve.

Journal Article↗
PubMed2005

Dynamics of COPII vesicles and the Golgi apparatus in cultured Nicotiana tabacum BY-2 cells provides evidence for transient association of Golgi stacks with endoplasmic reticulum exit sites.

Despite the ubiquitous presence of the COPI, COPII, and clathrin vesicle budding machineries in all eukaryotes, the organization of the secretory pathway in plants differs significantly from that in yeast and mammalian cells. Mobile Golgi stacks and the lack of both transitional endoplasmic reticulum (ER) and a distinct ER-to-Golgi intermediate compartment are the most prominent distinguishing morphological features of the early secretory pathway in plants. Although the formation of COPI vesicles at periphery of Golgi cisternae has been demonstrated in plants, exit from the ER has been difficult to visualize, and the spatial relationship of this event is now a matter of controversy. Using tobacco (Nicotiana tabacum) BY-2 cells, which represent a highly active secretory system, we have used two approaches to investigate the location and dynamics of COPII binding to the ER and the relationship of these ER exit sites (ERES) to the Golgi apparatus. On the one hand, we have identified endogenous COPII using affinity purified antisera generated against selected COPII-coat proteins (Sar1, Sec13, and Sec23); on the other hand, we have prepared a BY-2 cell line expressing Sec13:green fluorescent protein (GFP) to perform live cell imaging with red fluorescent protein-labeled ER or Golgi stacks. COPII binding to the ER in BY-2 cells is visualized as fluorescent punctate structures uniformly distributed over the surface of the ER, both after antibody staining as well as by Sec13:GFP expression. These structures are smaller and greatly outnumber the Golgi stacks. They are stationary, but have an extremely short half-life (<10 s). Without correlative imaging data on the export of membrane or lumenal ER cargo it was not possible to equate unequivocally these COPII binding loci with ERES. When a GDP-fixed Sar1 mutant is expressed, ER export is blocked and the visualization of COPII binding is perturbed. On the other hand, when secretion is inhibited by brefeldin A, COPII binding sites on the ER remain visible even after the Golgi apparatus has been lost. Live cell imaging in a confocal laser scanning microscope equipped with spinning disk optics allowed us to investigate the relationship between mobile Golgi stacks and COPII binding sites. As they move, Golgi stacks temporarily associated with COPII binding sites at their rims. Golgi stacks were visualized with their peripheries partially or fully occupied with COPII. In the latter case, Golgi stacks had the appearance of a COPII halo. Slow moving Golgi stacks tended to have more peripheral COPII than faster moving ones. However, some stationary Golgi stacks entirely lacking COPII were also observed. Our results indicate that, in a cell type with highly mobile Golgi stacks like tobacco BY-2, the Golgi apparatus is not continually linked to a single ERES. By contrast, Golgi stacks associate intermittently and sometimes concurrently with several ERES as they move.

Binding Sites↗
PubMed2005

PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 is a plant-specific SEC12-related protein that enables the endoplasmic reticulum exit of a high-affinity phosphate transporter in Arabidopsis.

PHOSPHATE TRANSPORTER1 (PHT1) genes encode phosphate (Pi) transporters that play a fundamental role in Pi acquisition and remobilization in plants. Mutation of the Arabidopsis thaliana PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 (PHF1) impairs Pi transport, resulting in the constitutive expression of many Pi starvation-induced genes, increased arsenate resistance, and reduced Pi accumulation. PHF1 expression was detected in all tissues, particularly in roots, flowers, and senescing leaves, and was induced by Pi starvation, thus mimicking the expression patterns of the whole PHT1 gene family. PHF1 was localized in endoplasmic reticulum (ER), and mutation of PHF1 resulted in ER retention and reduced accumulation of the plasma membrane PHT1;1 transporter. By contrast, the PIP2A plasma membrane protein was not mislocalized, and the secretion of Pi starvation-induced RNases was not affected in the mutant. PHF1 encodes a plant-specific protein structurally related to the SEC12 proteins of the early secretory pathway. However, PHF1 lacks most of the conserved residues in SEC12 proteins essential as guanine nucleotide exchange factors. Although it functions in early secretory trafficking, PHF1 likely evolved a novel mechanism accompanying functional specialization on Pi transporters. The identification of PHF1 reveals that plants are also endowed with accessory proteins specific for selected plasma membrane proteins, allowing their exit from the ER, and that these ER exit cofactors may have a phylum-specific origin.

Amino Acid Sequence↗
PubMed1999

Towards an exit wave in closed analytical form.

A simple but sufficiently accurate expression is obtained for the exit wave of a crystal in zone-axis orientation. The exit wave at each atom column can be parametrized with only one parameter, which is a function of the projected 'weight' of the column.

Journal Article↗
PubMed1997

Anopheles gambiae gonotrophic cycle duration, biting and exiting behaviour unaffected by permethrin-impregnated bednets in The Gambia.

Permethrin-impregnated bednets protect children against malaria in The Gambia, where Anopheles gambiae complex mosquitoes are the main vectors of malaria. However, no effect has been found on mosquito density, parous rates or sporozoite rates in An.gambiae sensu lato populations; only a reduction in the numbers of mosquitoes resting indoors in rooms with treated bednets. A possible explanation for this paradox is that exposure to treated bednets leads to changed vector behaviour such as a shift in biting time, a diversion to biting outdoors instead of indoors, to biting animals instead of humans, or to increased duration of the gonotrophic cycle. To investigate these possibilities, we observed the biting and existing behaviour of An.gambiae in ten pairs of villages, in half of which the residents used permethrin-treated bednets. The possible influence of treated bednets on the gonotrophic cycle length was evaluated by mark-release-recapture experiment. No significant difference was found between villages with treated and untreated bednets in the indoor/outdoor ratio of human biting, in mean biting times or in human blood indices of An.gambiae females found resting indoors in the mornings. The proportions of unfed, fed or gravid An.gambiae females collected in exit traps, and the number of females exiting showed no significant differences between rooms with treated and untreated bednets. Indications for a gonotrophic cycle length of 2 days were found. No evidence for any change in duration of the gonotrophic cycle in relation to exposure to treated bednets was found, although the number of recaptures was low in the villages with treated bednets. Since equal numbers of infective An.gambiae were found in villages with treated or untreated bednets, and no changes in mosquito behaviour were detected, we cannot account for how children are protected against malaria by treated bednets. One possibility is that mosquitoes divert to bite other hosts, including adults.

Animals↗
PubMed1992

Chinese medical school exit objectives: a multi-institutional survey of teacher opinion.

This paper describes a collaborative survey of Chinese medical school teacher opinion concerning clinical behaviours and skills that Chinese students should be expected to demonstrate prior to graduation from medical school. Selected teachers from four Chinese medical schools indicated whether each of 77 objectives was: essential for every student to know or demonstrate prior to graduation; useful but not essential; or not applicable to their educational programmes. Results show teachers' expectations regarding some of the behaviours and skills Chinese medical school teachers consider to be important for students to learn. Forty-nine per cent of the exit objectives were regarded as essential by 75% or more of the teachers. The most essential objectives involved performing clinical procedures, collaborating and communicating with health care professionals, conducting organ system examinations, formulating hypotheses and defining problems. Other essential objectives were concerned with communicating with patients and their families, maintaining currency within the discipline, and recognition, evaluation and triage of patients with life-threatening or chronic conditions. Exit objectives related to health promotion and risk assessment were regarded as useful but not essential at the undergraduate level. Implications for Chinese medical education are discussed.

China↗
PubMed1980

Exit block in myxedema, treated effectively by thyroid hormone therapy.

A case of a 71-year-old female who developed exit block one year after implantation of a pervenous pacemaker is reported. The pacemaker had been implanted for sick sinus syndrome; the exit block was probably due to the development of severe myxedema which caused high pacing threshold. Normal pacing threshold was obtained on the seventh day of adequate thyroid hormone therapy and a follow-up one year later revealed effective control of the myxedema and no abnormalities in the function of the pacemaker system.

Aged↗
PubMed2006

Surveillance cultures of tunneled cuffed catheter exit sites in chronic hemodialysis patients are of no benefit.

Catheter-related infections are a major cause of morbidity and mortality in hemodialysis (HD) patients. This study evaluated the utility of surveillance swab cultures (Ssc) of tunneled cuffed catheter (TCC) exit sites as a prediction and prevention strategy for infection. A 6-month prospective-controlled trial with 94 chronic HD patients with a TCC who received monthly Ssc and were stratified by dialysis day into topical therapy based on Ssc results (Group A) or no therapy (Group B). Outcomes were exit site infection (ESI) and catheter-associated bacteremia (CAB). The overall monthly prevalence of positive Ssc was 14.9%. There was no difference in the number of positive Ssc (17.7% vs. 11.6%, p > 0.05) or ESI (19.6% vs.16.3%, p > 0.05) between Groups A and B, respectively. Catheter-associated bacteremia was higher in Group A (17.7% vs. 4.7%, p = 0.05). There were significantly more ESI in the patients treated for a positive Ssc. In Group A, the incidence of ESI was significantly higher in those treated for a positive vs. negative Ssc (55% vs. 12%, p = 0.009) and CAB rates trended higher with positive Ssc (22.2% vs. 16.7%, p > 0.05). The strategy of treating positive surveillance cultures is not beneficial. Positive Ssc do not predict the occurrence of catheter-related infection, and treatment of these cultures may lead to increased infection rates.

Aged↗
PubMedDate not supplied

Buildup/surface dose and exit dose measurements for a 6-MV linear accelerator.

The central axis dose distribution in the buildup region for the Varian Clinac 6/100 6-MV x-ray beam was measured in a polystyrene phantom using a fixed volume (0.5 cm3) parallel-plate ionization chamber (2.4-mm plate separation). Results for the surface dose measurements ranged from approximately 8% of the maximum dose for a 5 X 5 cm field, up to 36% for a 40 X 40 cm field, 100-cm source-skin distance. The effect of a 0.6-cm-thick polycarbonate blocking tray and metal filters on the surface and buildup dose is also reported. In addition, ionization measurements were made to document the dose perturbations caused by the absence of backscattering material at the exit surface of a polystyrene phantom. Exit dose measurements showed a 15% reduction in dose with essentially no scattering material beyond the measurement point. Near full scatter condition could be restored by placing 5-10 mm (depending on field size) of unit density material directly behind the ion chamber's distal surface.

Humans↗
PubMed1998

Effective dose in diagnostic radiology as a function of x-ray beam filtration for a constant exit dose and constant film density.

Individual organ absorbed dose and total effective dose for nine common radiographic projections were investigated as a function of half-value-layer, HVL, and total equivalent filtration for the following cases: (1) with the patient exit dose held constant and (2) with the film density held constant. As expected, the absorbed dose to organs proximal to the x-ray beam entry point tracked with skin dose as a function of HVL, whereas organ dose distal to the x-ray beam entry point was almost independent of HVL. Dose to organs near mid-line showed an intermediate HVL dependence. For the nine radiographic projections, increasing the total filtration from 1.5 to 4.0 mm Al while holding the kVp fixed resulted in mean decreases in the effective dose of 17% for the case of a constant exit dose, and 25% for a constant film density with a "400 speed" rare-earth screen-film system. The decreases in the mean skin entrance doses were 38% and 45%, respectively. With the screen-film system, the average effective dose decreased at 16% per mm of added Al between 1.5 and 2.5 mm Al total filtration, and at 7% per mm between 2.5 and 4.0 mm. These results partially support the NCRP Report No. 102 recommendation that the minimum filtration be 2.5 mm Al for general diagnostic x-ray tubes. They also suggest, using the linear no-threshold radiation risk model, that further significant reductions in stochastic risk to the U.S. population can be achieved by raising the minimum beyond 2.5 mm. Experience over a 12 year period in our tertiary care teaching hospital indicates that adding 1-1.5 mm Al filtration beyond the 2.5 mm minimum does not pose a problem in terms of additional tube loading or reduction in image quality. However, these issues need to be more formally addressed.

Abdomen↗
PubMed2000

Monte Carlo studies of the exit photon spectra and dose to a metal/phosphor portal imaging screen.

The energy spectra and the dose to a Cu plate/Gd2O2S phosphor portal imaging detector were investigated for monoenergetic incident beams of photons (1.25, 2, and 5 MeV). The Monte Carlo method was used to characterize the influence of the patient/detector geometry, detector material and design, and incident beam energy on the spectral distribution and the dose, at the imaging detector plane, of a photon beam scattered from a water phantom. The results show that radiation equilibrium is lost in the air gap and that, for the geometries studied, this effect led to a reduction in the exit dose of up to 40%. The finding that the effects of the air gap and field size are roughly complementary has led to the hypothesis that an equivalent field size concept may be used to account for intensity and spectral changes arising from air gap variations. The copper plate preferentially attenuates the low-energy scattered photons incident on it, while producing additional annihilation, bremsstrahlung, and scattered photons. As a result, the scatter spectra at the copper surface entrance of the detector differs significantly from that at the Cu/phosphor interface. In addition, the mean scattered photon energy at the interface was observed to be roughly 0.4 MeV higher than the corresponding effective energy for 2 MeV incident beams. A comparison of the dose to various detector materials showed that exit dosimetry errors of up to 24% will occur if it is assumed that the Cu plate/Gd2O2S phosphor detector is water equivalent.

Computer Simulation↗
PubMed1977

Different binding sites for entry and exit of amino acids in whole cells of Mycobacterium phlei.

On the basis of mutual inhibition of uptake with different amino acids in whole cells of Mycobacterium phlei, it was demonstrated that the binding site of proline was different from those of all other amino acids studied. Other groups of amino acids share a common binding site: lysine, histidine, and arginine; valine, leucine, and isoleucine; tryptophan, tyrosine, and phenylalanine; glutamic acid and aspartic acid. The exit and entry processes were studied for proline, glutamine, and glutamic acid. It was observed that in each case the entry and exit processes were mediated by different membrane sites.

Amino Acids↗