Occluded or Not?: A Subtle Electrocardiographic Answer.
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ABSTRACT:
SUBMITTER: Plane AF
PROVIDER: S-EPMC8288577 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We recently described two opposing states of transcriptional competency. One is termed 'competent' whereby a gene is capable of responding to trans-acting transcription factors of the cell, such that it is active if appropriate transcriptional activators are present, though it can also be silent if activators are absent or repressors are present. The other is termed 'occluded' whereby a gene is silenced by cis-acting, chromatin-based mechanisms in a manner that blocks it from responding to trans-acting factors, such that it is silent even when activators are present in the cellular milieu. We proposed that gene occlusion is a mechanism by which differentiated cells stably maintain their phenotypic identities. Here, we describe chromatin analysis of occluded genes. We found that DNA methylation plays a causal role in maintaining occlusion for a subset of occluded genes. We further examined a variety of other chromatin marks typically associated with transcriptional silencing, including histone variants, covalent histone modifications and chromatin-associated proteins. Surprisingly, we found that although many of these marks are robustly linked to silent genes (which include both occluded genes and genes that are competent but silent), none is linked specifically to occluded genes. Although the observation does not rule out a possible causal role of these chromatin marks in occlusion, it does suggest that these marks might be secondary effect rather than primary cause of the silent state in many genes.
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Project description:The lactose permease of Escherichia coli (LacY) utilizes an alternating access symport mechanism with multiple conformational intermediates, but only inward (cytoplasmic)- or outward (periplasmic)-open structures have been characterized by X-ray crystallography. It is demonstrated here with sugar-binding studies that cross-linking paired-Cys replacements across the closed cytoplasmic cavity stabilize an occluded conformer with an inaccessible sugar-binding site. In addition, a nanobody (Nb) that stabilizes a periplasmic-open conformer with an easily accessible sugar-binding site in WT LacY fails to cause the cytoplasmic cross-linked mutants to become accessible to galactoside, showing that the periplasmic cavity is closed. These results are consistent with tight association of the periplasmic ends in two pairs of helices containing clusters of small residues in the packing interface between N- and C-terminal six-helix bundles of the symporter. However, after reduction of the disulfide bond, the Nb markedly increases the rate of galactoside binding, indicating unrestricted access to the Nb epitope and the galactoside-binding site from the periplasm. The findings indicate that the cross-linked cytoplasmic double-Cys mutants resemble an occluded apo-intermediate in the transport cycle.
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Project description:BACKGROUND: Wallstents (Schneider Stent, Inc., USA) used for the palliation of malignant biliary strictures, although associated with prolonged patency, can occlude. There is no consensus regarding the optimal management of Wallstent occlusion. AIMS: To evaluate the efficacy of different endoscopic methods for managing biliary Wallstent occlusion. METHODS: A multicentre retrospective study of patients managed for a biliary Wallstent occlusion. RESULTS: Data were available for 38 patients with 44 Wallstent occlusions, all of which had initial endoscopic management. Twenty four patients had died and 14 were alive after a median follow up of 231 (30-1095) days following Wallstent occlusion. Occlusions were managed by insertion of another Wallstent in 19, insertion of a plastic stent in 20, and mechanical cleaning in five. Endoscopic management was successful in 43 (98%). Following management of the occlusion, bilirubin decreased from 6.0 (0.5-34.3) to 2.1 (0.2-27.7) mg/100 ml (p < 0.05). No complications occurred. The median duration of second stent patency was 75 days (95% confidence interval 43 to 107) after insertion of another Wallstent, 90 days (71 to 109) after insertion of a plastic stent, and 34 days (30 to 38) after mechanical cleaning (NS). The respective median survivals were 70 days (22-118), 98 days (54-142), and 34 days (30-380) (NS). Incremental cost effective analysis showed that plastic stent insertion is the most cost effective option. CONCLUSION: Although all three methods are equally effective in managing an occluded Wallstent, the most cost effective method appears to be plastic stent insertion.
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Project description:PURPOSE:To develop a methodology for cannulating porcine retinal venules using a robotic assistive arm after inducing a retinal vein occlusion using the photosensitizer rose bengal. METHODOLOGY:Retinal vein occlusions proximal to the first vascular branch point were induced following intravenous injection of rose bengal by exposure to 532nm laser light delivered by slit-lamp or endolaser probe. Retinal veins were cannulated by positioning a glass catheter tip using a robotically controlled micromanipulator above venules with an outer diameter of 80?m or more and performing a preset piercing maneuver, controlled robotically. The ability of a balanced salt (BSS) solution to remove an occlusion by repeat distention of the retinal vein was also assessed. RESULTS:Cannulation using the preset piercing program was successful in 9 of 9 eyes. Piercing using the micromanipulator under manual control was successful in only 24 of 52 attempts, with several attempts leading to double piercing. The best location for cannulation was directly proximal to the occlusion. Infusion of BSS did not result in the resolution of the occlusion. CONCLUSION:Cannulation of venules using a robotic microassistive arm can be achieved with consistency, provided the piercing is robotically driven. The model appears robust enough to allow testing of therapeutic strategies aimed at eliminating a retinal vein thrombus and its evolution over time.
| S-EPMC5046264 | biostudies-literature
Project description:Objectives Direct intrahepatic portosystemic shunt (DIPS) stent placement is an effective treatment for patients with Budd-Chiari syndrome (BCS); however, thrombotic occlusion of DIPS stent remains a cause of concern. The purpose of this study is to describe a novel technique of balloon-occluded-thrombolysis (BOT) for occluded DIPS stent, and compare it with the conventional catheter-directed-thrombolysis (CDT). Methods In this retrospective study, the hospital database was searched for BCS patients who underwent DIPS revision for thrombotic stent occlusion between January 2015 and February 2021. Patients were divided into CDT group and BOT group. The groups were compared for technical success, total dose of thrombolytic agent administered, duration of hospital stay, and primary assisted stent patency rates at 1- and 6-month follow-up. Results CDT was performed in 12 patients, whereas 21 patients underwent BOT. Complete recanalization was achieved in 66.7% (8 of 12) patients of CDT group as compared to 81% (17 of 21) patients of BOT group (nonsignificant difference, p = 0.420). BOT group had a short hospital stay (1.8 ± 0.7 vs. 3.5 ± 1.0 days) and required less dose of thrombolytic agent ([2.2 ± 0.4]x10 5 IU versus [8.3 ± 2.9]x10 5 IU of urokinase) as compared to the CDT group and both differences were statistically significant ( p < 0.001). Further, 6-month patency rate was higher in BOT group as compared to CDT group ( p = 0.024). Conclusion The novel BOT technique of DIPS revision allows longer contact time of thrombolytic agent with the thrombi within the occluded stent. This helps in achieving fast recanalization of thrombosed DIPS stent with a significantly less dose of thrombolytic agent required, thus reducing the risk of systemic complications associated with thrombolytic administration.
| S-EPMC10723961 | biostudies-literature
Project description:Image sequences of live proliferating cells often contain visual ambiguities that are difficult even for human domain experts to resolve. Here we present a new approach to analyzing image sequences that capture the development of clones of hematopoietic stem cells (HSCs) from live cell time lapse microscopy. The HSCs cannot survive long term imaging unless they are cultured together with a secondary cell type, OP9 stromal cells. The HSCs frequently disappear under the OP9 cell layer, making segmentation difficult or impossible from a single image frame, even for a human domain expert. We have developed a new approach to the segmentation of HSCs that captures these occluded cells. Starting with an a priori segmentation that uses a Monte Carlo technique to estimate the number of cells in a clump of touching cells, we proceed to track and lineage the image data. Following user validation of the lineage information, an a posteriori resegmentation step utilizing tracking results delineates the HSCs occluded by the OP9 layer. Resegmentation has been applied to 3031 occluded segmentations from 77 tracks, correctly recovering over 84% of the occluded segmentations.
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Project description:IntoductionLeriche syndrome is a special type of obliterating arterial disease of the lower limbs which results in thrombotic occlusion of the aortoiliac junction.Case reportWe report the case of a 65-year-old patient with known cardiovascular and nephrological pathological history, who presented with acute abdominal pain with intermittent claudication of the lower limbs and in whom clinical examination found abolition of the femoral pulses.DiscussionDoppler ultrasound of the abdominal aorta revealed aortic thrombosis in the lower of the renal segment extended to the iliac bifurcation with damping of upstream circulatory speeds. We supplemented with a CT angiography of the aorta and lower limbs which demonstrated extensive arterial thrombosis from the abdominal aorta to the bilateral external iliac arteries.
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Project description:Occlusion-derived virions (ODVs) of the nucleopolyhedrovirus of Culex nigripalpus (CuniNPV) were purified by Ludox density gradient ultracentrifugation, and the proteins were separated by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Proteins were identified by using Edman sequencing, matrix-assisted laser desorption ionization-time of flight mass spectrometry, nanoelectrospray quadrupole time-of-flight mass spectrometry, or a combination of these methods. Half of the 44 polypeptide sequences identified in this analysis were unique open reading frames (ORFs) encoded by the CuniNPV genome and did not show similarity to any other sequences present in protein databases. Of the 22 polypeptides that showed similarities to other baculovirus-encoded proteins, only 17 sequences have previously been identified as structural proteins. The newly identified CuniNPV structural proteins cun058, cun059, cun087, cun106, and cun109 are homologues of Autographa californica nucleopolyhedrovirus (AcMNPV) ORFs 68, 62, 98, 81, and 2, respectively. The products of four genes, namely, lef-1 (cun045), alkaline exonuclease (cun054), helicase (cun089), and DNA polymerase (cun091), were not detected in the CuniNPV ODV preparations. These four genes are conserved among all annotated baculovirus genomes, and their homologues have been detected in the ODV of AcMNPV.
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