COOH-terminal (S3) domains are conserved within the MscL family of bacterial mechanosensitive channels, but their function remains unclear. The X-ray structure of MscL from Mycobacterium tuberculosis (TbMscL) revealed cytoplasmic domains forming a pentameric bundle (Chang, G., R.H. Spencer, A.T. Lee, M.T. Barclay, and D.C. Rees. 1998. Science. 282:2220–2226). The helices, however, have an unusual orientation in which hydrophobic sidechains face outside while charged residues face inside, possibly due to specific crystallization conditions. Based on the structure of pentameric cartilage protein , we modeled the COOH-terminal region of E. coli MscL to better satisfy the hydrophobicity criteria, with sidechains of conserved aliphatic residues all inside the bundle. Molecular dynamic simulations predicted higher stability for this conformation compared with one modeled after the crystal structure of TbMscL, and suggested distances for disulfide trapping experiments. The single cysteine mutants L121C and I125C formed dimers under ambient conditions and more so in the presence of an oxidant. The double-cysteine mutants, L121C/L122C and L128C/L129C, often cross-link into tetrameric and pentameric structures, consistent with the new model. Patch-clamp examination of these double mutants under moderately oxidizing or reducing conditions indicated that the bundle cross-linking neither prevents the channel from opening nor changes thermodynamic parameters of gating. Destabilization of the bundle by replacing conservative leucines with small polar residues, or complete removal of COOH-terminal domain (Δ110–136 mutation), increased the occupancy of subconducting states but did not change gating parameters substantially. The Δ110–136 truncation mutant was functional in in vivo osmotic shock assays; however, the amount of ATP released into the shock medium was considerably larger than in controls. The data strongly suggest that in contrast to previous gating models (Sukharev, S., M. Betanzos, C.S. Chiang, and H.R. Guy. 2001a. Nature. 409:720–724.), S3 domains are stably associated in both closed and open conformations. The bundle-like assembly of cytoplasmic helices provides stability to the open conformation, and may function as a size-exclusion filter at the cytoplasmic entrance to the MscL pore, preventing loss of essential metabolites.
Vascular anomalies, including vascular malformations and tumors, are frequently straightforward to detect; however, accurate diagnosis and appropriate treatment are often challenging. Misdiagnosis of these lesions can lead clinicians in the wrong direction when treating these patients, which can have unfavorable results. This review presents an overview of the classification systems that have been developed for the diagnosis of vascular lesions with a focus on the imaging characteristics. Pictorial examples of each lesion on physical examination, as well as non-invasive and minimally invasive imaging are presented. An overview of the endovascular treatment of these lesions is also given. In some cases, vascular anomalies may be associated with an underlying syndrome and several of the most commonly encountered syndromes are discussed. Understanding of the classification systems, familiarity with the treatment options and knowledge of the associated syndromes are essential for all physicians working with this patient population. The approach to the described entities necessitates an organized multi-disciplinary team effort, with diagnostic imaging playing an increasingly important role in the proper diagnosis and a combined interventional radiologic and surgical treatment method showing promising results.
The membership of the Society of Interventional Radiology (SIR) Standards of Practice Committee represents experts in a broad spectrum of interventional procedures from the private and academic sectors of medicine. Generally, Standards of Practice Committee members dedicate the vast majority of their professional time to performing interventional procedures; as such, they represent a valid broad expert constituency of the subject matter under consideration for standards production.Technical documents specifying the exact consensus and literature review methodologies as well as the institutional affiliations and professional credentials of the authors of this document are available upon request from SIR, 3975 Fair Ridge Dr., Suite 400 N., Fairfax, VA 22033. METHODOLOGYSIR produces its Standards of Practice documents using the following process. Standards documents of relevance and timeliness are conceptualized by the Standards of Practice Committee members. A recognized expert is identified to serve as the principal author for the standard. Additional authors may be assigned dependent upon the magnitude of the project.An in-depth literature search is performed using electronic medical literature databases. Then, a critical review of peer-reviewed articles is performed with regard to the study methodology, results, and conclusions. The qualitative weight of these articles is assembled into an evidence table, which is used to write the document such that it contains evidence-based data with respect to content, rates, and thresholds (Fig E1 and Table E1, available online at www.jvir.org).When the evidence of literature is weak, conflicting, or contradictory, consensus for the parameter is reached by a minimum of 12 Standards of Practice Committee members using a modified Delphi consensus method (Appendix A). For purposes of these documents, consensus is defined as 80% Delphi participant agreement on a value or parameter.The draft document is critically reviewed by the Standards of Practice Committee members by telephone conference calling or face-to-face meeting. The finalized draft from the Committee is sent to the SIR membership for further input/criticism during a 30-day comment period. These comments are discussed by the Standards of Practice Committee, and appropriate revisions are made to create the finished standards document. Prior to its publication, the document is endorsed by the SIR Executive Council.
Objective As the utility of Child-Pugh (C-P) class is limited by the subjectivity of ascites and encephalopathy, we evaluated a previously established objective method, the albumin-bilirubin (ALBI) grade, as a prognosticator for yttrium-90 radioembolization (RE) treatment for patients with hepatocellular carcinoma (HCC). Materials and Methods A total of 117 patients who received RE for HCC from 2 academic centers were reviewed and stratified by ALBI grade, C-P class, and Barcelona Clinic Liver Cancer stage. The overall survival (OS) according to these 3 criteria was evaluated by Kaplan-Meier survival analysis. The utilities of C-P class and ALBI grade as prognostic indicators were compared using the log-rank test. Multivariate Cox regression analysis was performed to identify additional predictive factors. Results Patients with ALBI grade 1 (n = 49) had superior OS than those with ALBI grade 2 (n = 65) (P = 0.01). Meanwhile, no significant difference was observed in OS between C-P class A (n = 100) and C-P class B (n = 14) (P = 0.11). For C-P class A patients, the ALBI grade (1 vs. 2) was able to stratify 2 clear and nonoverlapping subgroups with differing OS curves (P = 0.03). Multivariate Cox regression test identified alanine transaminase, Barcelona Clinic Liver Cancer stage, and ALBI grade as the strongest prognostic factors for OS (P < 0.10). Conclusions ALBI grade as a prognosticator has demonstrated clear survival discrimination that is superior to C-P class among HCC patients treated with RE, particularly within the subgroup of C-P class A patients. ALBI grade is useful for clinicians to make decisions as to whether RE should be recommended to patients with HCC.
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