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Nucleic Acids Research Nov 2000Error-free lesion bypass and error-prone lesion bypass are important cellular responses to DNA damage during replication, both of which require a DNA polymerase (Pol)....
Error-free lesion bypass and error-prone lesion bypass are important cellular responses to DNA damage during replication, both of which require a DNA polymerase (Pol). To identify lesion bypass DNA polymerases, we have purified human Polkappa encoded by the DINB1 gene and examined its response to damaged DNA templates. Here, we show that human Polkappa is a novel lesion bypass polymerase in vitro. Purified human Polkappa efficiently bypassed a template 8-oxoguanine, incorporating mainly A and less frequently C opposite the lesion. Human Polkappa most frequently incorporated A opposite a template abasic site. Efficient further extension required T as the next template base, and was mediated mainly by a one-nucleotide deletion mechanism. Human Polkappa was able to bypass an acetylaminofluorene-modified G in DNA, incorporating either C or T, and less efficiently A opposite the lesion. Furthermore, human Polkappa effectively bypassed a template (-)-trans-anti-benzo[a]pyrene-N:(2)-dG lesion in an error-free manner by incorporating a C opposite the bulky adduct. In contrast, human Polkappa was unable to bypass a template TT dimer or a TT (6-4) photoproduct, two of the major UV lesions. These results suggest that Polkappa plays an important role in both error-free and error-prone lesion bypass in humans.
Topics: 2-Acetylaminofluorene; Base Pair Mismatch; Base Sequence; Benzo(a)pyrene; Catalysis; DNA Adducts; DNA Damage; DNA-Directed DNA Polymerase; Guanine; Humans; Mutagenesis; Mutagens; Nucleotides; Proteins; Pyrimidine Dimers; Recombinant Fusion Proteins; Substrate Specificity; Templates, Genetic
PubMed: 11058110
DOI: 10.1093/nar/28.21.4138 -
European Journal of Vascular and... Jul 2011Compare the outcome of distal (bypass to the crural arteries) versus ultradistal (bypass to the pedal arteries) bypasses in patients with critical leg ischaemia (CLI). (Comparative Study)
Comparative Study
OBJECTIVES
Compare the outcome of distal (bypass to the crural arteries) versus ultradistal (bypass to the pedal arteries) bypasses in patients with critical leg ischaemia (CLI).
DESIGN
Retrospective analysis of prospectively collected data of patients with CLI undergoing infra-popliteal bypass surgery is performed.
MATERIALS AND METHODS
Patients undergoing infra-popliteal bypass at a single institution between 2004 and 2010 are included. Patency rates at 1-year and amputation-free survival at 12 and 48 months are analysed.
RESULTS
Two hundred and thirty bypasses were performed in 209 consecutive patients (156 men, median age; 76 years, range; 19-96 years). One hundred and seventy nine (78%) bypass were classified as distal and 51 (22%) as ultradistal. The incidence of diabetes mellitus was significantly higher in the ultradistal group (p=0.0025). At 1-year, the distal group primary, assisted-primary and secondary patency rates were 61.7%, 83.1% and 87.4% compared to 61.9%, 87.4% and 87.4% in the ultradistal group respectively. Amputation-free survival at 12 and 48 months was 82.9% and 61.5% in the distal group compared to 83.0% and 64.9% in the ultradistal group.
CONCLUSIONS
This study show that both distal and ultradistal bypass have comparable outcome regardless of the co-morbidities. The authors believe that elderly patients should be offered ultradistal bypass if indicated to avoid major amputation.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Amputation, Surgical; Arterial Occlusive Diseases; Chi-Square Distribution; Comorbidity; Critical Illness; Disease-Free Survival; Female; Humans; Ischemia; Kaplan-Meier Estimate; Limb Salvage; London; Lower Extremity; Male; Middle Aged; Patient Selection; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Grafting; Vascular Patency; Young Adult
PubMed: 21514854
DOI: 10.1016/j.ejvs.2011.03.016 -
Frontiers in Surgery 2022Moyamoya disease (MMD) is a chronic, progressive cerebrovascular disease involving the occlusion or stenosis of the terminal portion of the internal carotid artery (ICA)... (Review)
Review
Moyamoya disease (MMD) is a chronic, progressive cerebrovascular disease involving the occlusion or stenosis of the terminal portion of the internal carotid artery (ICA) and the proximal anterior and middle cerebral arteries. Adults with MMD have been shown to progressively accumulate neurological and cognitive deficits without treatment, with a mortality rate double that of pediatric patients with MMD. Surgical intervention is the mainstay of treatment to prevent disease progression and improve clinical outcomes. Several different types of bypasses can be utilized for revascularization in MMD, including indirect, direct, and combined forms of extracranial-to-intracranial (EC-IC) bypass. Overall, the choice of appropriate technique requires consideration of the age of the patient, preoperative hemodynamics, neurologic status, and territories most at risk and in need of revascularization. Here, we will review the indications and surgical techniques for the treatment of adult MMD. Step-by-step instructions for performing several bypass variants with technical pearls are discussed.
PubMed: 36061058
DOI: 10.3389/fsurg.2022.966430 -
Methodist DeBakey Cardiovascular Journal 2014Microsurgery for brain aneurysms is a current relevant technique, as advances in endovascular and stent-assisted coiling have not solved many of the difficulties... (Review)
Review
Microsurgery for brain aneurysms is a current relevant technique, as advances in endovascular and stent-assisted coiling have not solved many of the difficulties inherent in the management of complex brain aneurysms. The following review highlights the importance of microsurgical bypass techniques for the management of complex cerebrovascular aneurysms and emphasizes, through two clinical cases, the technical difficulties and indications for bypass surgery. These cases demonstrate that in selected scenarios, bypass microsurgery still offers the only viable treatment for complex aneurysms.
Topics: Aneurysm, Ruptured; Embolization, Therapeutic; Endovascular Procedures; Humans; Intracranial Aneurysm; Microsurgery; Neurosurgical Procedures; Plastic Surgery Procedures; Subarachnoid Hemorrhage; Vascular Surgical Procedures
PubMed: 25624977
DOI: 10.14797/mdcj-10-4-224 -
American Journal of Public Health Mar 2023To describe minors' use of judicial bypass to access abortion and the percentage of bypass petitions denied in Florida and Texas. Data were derived from official state...
To describe minors' use of judicial bypass to access abortion and the percentage of bypass petitions denied in Florida and Texas. Data were derived from official state statistics on judicial bypasses and abortions by age in Texas and Florida; abortions in Texas among minor nonresidents were estimated. In addition, judicial bypass petitions as a percentage of abortions received by minors and judicial bypass denials as a percentage of petitions were calculated. Between 2018 and 2021, minors received 5527 abortions in Florida and an estimated 5220 abortions in Texas. Use of judicial bypass was stable at 14% to 15% in Florida and declined from 14% to 10% in Texas. Among petitions for judicial bypass, denials increased in Florida from 6% to a maximum of 13% and remained stable in Texas at 5% to 7%. Minors' use of judicial bypass in Texas and Florida is substantial. The percentage of denials is higher and increasing in Florida. Minors who need confidential abortion care may now be forced to seek judicial bypass far from home. Parental involvement laws in states that do not ban abortion will compound barriers to abortion care. (. 2023;113(3):316-319. https://doi.org/10.2105/10.2105/AJPH.2022.307173).
Topics: Pregnancy; Female; Humans; United States; Parental Consent; Minors; Judicial Role; Texas; Florida; Abortion, Induced; Abortion, Legal
PubMed: 36634290
DOI: 10.2105/AJPH.2022.307173 -
Scientific Reports Dec 2022L-nucleosides were the most important antiviral lead compounds because they can inhibit viral DNA polymerase and DNA synthesis of many viruses, whereas they may lead...
L-nucleosides were the most important antiviral lead compounds because they can inhibit viral DNA polymerase and DNA synthesis of many viruses, whereas they may lead to mutations in DNA replication and cause genomic instability. In this study, we reported the replicative bypass of L-deoxynucleosides in recombinant DNA by restriction enzyme-mediated assays to examine their impact on DNA replication in vitro and in E. coli cells. The results showed that a template L-dC inhibited Taq DNA polymerase reaction, whereas it can be bypassed by Vent (exo) DNA polymerase as well as in cell replication, inserting correct nucleotides opposite L-dC. L-dG can be bypassed by Taq DNA polymerase and in E. coli cells, maintaining insertion of correct incoming nucleotides, and L-dG induced mutagenic replication by Vent (exo) DNA polymerase. In contrast, L-dA can induced mutagenic replication in vitro and in E. coli cells. MD simulations were performed to investigate how DNA polymerase affected replicative bypass and mutations when D-nucleosides replaced with L-nucleosides. This study will provide a basis for the ability to assess the cytotoxic and mutagenic properties of the L-nucleoside drugs.
Topics: Escherichia coli; Taq Polymerase
PubMed: 36476762
DOI: 10.1038/s41598-022-24802-5 -
PloS One 2022Femoro-popliteal bypass with autologous vascular graft is a key revascularization method in chronic limb-threatening ischemia (CLTI). However, the lack of suitable...
INTRODUCTION
Femoro-popliteal bypass with autologous vascular graft is a key revascularization method in chronic limb-threatening ischemia (CLTI). However, the lack of suitable autologous conduit may occur in 15-45% of the patients, necessitating the implantation of prosthetic or allogen grafts. Only little data is available on the outcome of allograft use in CLTI.
AIMS
Our objective were to evaluate the long term results of infrainguinal allograft bypass surgery in patients with chronic limb-threatening ischemia (CLTI) and compare the results of arterial and venous allografts.
METHODS
Single center, retrospective study analysing the outcomes of infrainguinal allograft bypass surgery in patients with CLTI between January 2007 and December 2017.
RESULTS
During a 11-year period, 134 infrainguinal allograft bypasses were performed for CLTI [91 males (67.9%)]. Great saphenous vein (GSV) was implanted in 100 cases, superficial femoral artery (SFA) was implanted in 34 cases. Early postoperative complications appeared in 16.4% of cases and perioperative mortality (<30 days) was 1.4%. Primary patency at one, three and five years was 59%, 44% and 41%, respectively, while secondary patency was 60%, 45% and 41%, respectively. Primary patency of the SFA allografts was significantly higher than GSV allografts (1 year: SFA: 84% vs. GSV: 51% p = 0,001; 3 years: SFA: 76% vs. GSV: 32% p = 0,001; 5 years: SFA: 71% vs. GSV: 30% p = 0.001). Both primary and secondary patency of SFA allograft implanted in below-knee position were significantly higher than GSV bypasses (p = 0.0006; p = 0.0005, respectively). Limb salvage at one, three and five years following surgery was 74%, 64% and 62%, respectively. Long-term survival was 53% at 5 years.
CONCLUSION
Allograft implantation is a suitable method for limb salvage in CLTI. The patency of arterial allograft is better than venous allograft patency, especially in below-knee position during infrainguinal allograft bypass surgery.
Topics: Male; Humans; Ischemia; Vascular Patency; Chronic Limb-Threatening Ischemia; Retrospective Studies; Saphenous Vein; Limb Salvage; Allografts; Treatment Outcome; Peripheral Arterial Disease; Risk Factors
PubMed: 36301873
DOI: 10.1371/journal.pone.0275628 -
American Journal of Cardiovascular... 2023This study aimed to investigate the correlation between the number of bypassed vessels, the duration of Cardiopulmonary bypass, blood transfusion requirements, revision...
OBJECTIVE
This study aimed to investigate the correlation between the number of bypassed vessels, the duration of Cardiopulmonary bypass, blood transfusion requirements, revision rates, and mortality outcomes. The objective was to get insights into the potential challenges that may arise during the postoperative phase.
METHODS
Our study covered a total of 677 patients from January 2015 to January 2021. The study and analysis focused on many factors including the surgical procedure, the number of bypassed vessels, transfusion requirements, comorbidities, revision rates, the administration of blood thinners, and early mortality.
RESULTS
Male patients numbered 513 and female patients 164. The combined coronary artery bypass grafting surgeries were 187, whereas the isolated ones were 490. Combination procedures traditionally used one- and two-vessel bypass grafting. 30.9% of patients had three vessels, while 31.6% had four. The typical blood transfusion has 4.2 erythrocytes. Fresh frozen plasma averaged 2.9 units, platelets 2.4 units, and whole fresh blood 2.6 units. The average cardiopulmonary bypass time was 145.1 and cross-clamp time was 89.3.
CONCLUSION
Six vessel bypasses have the highest revision rate. Transfusion rises with longer cardiopulmonary bypass and cross-clamp periods. Using acetylsalicylic acid before surgery increases the need for fresh frozen plasma and platelets. However, warfarin sodium increases the need for fresh frozen plasma and increases mortality. The revision highly linked with total CPB, cross-clamp times, all blood transfusions, and mortality.
PubMed: 38026113
DOI: No ID Found -
Toxicological Research Oct 2017Aryl hydrocarbons such as 3-nitrobenzanthrone (NBA), 4-aminobiphenyl (ABP), acetylaminofluorene (AAF), benzo(a)pyrene (BaP), and 1-nitropyrene (NP) form bulky DNA... (Review)
Review
Aryl hydrocarbons such as 3-nitrobenzanthrone (NBA), 4-aminobiphenyl (ABP), acetylaminofluorene (AAF), benzo(a)pyrene (BaP), and 1-nitropyrene (NP) form bulky DNA adducts when absorbed by mammalian cells. These chemicals are metabolically activated to reactive forms in mammalian cells and preferentially get attached covalently to the or C8 positions of guanine or the position of adenine. The proportion of and C8 guanine adducts in DNA differs among chemicals. Although these adducts block DNA replication, cells have a mechanism allowing to continue replication by bypassing these adducts: translesion DNA synthesis (TLS). TLS is performed by translesion DNA polymerases-Pol η, κ, ι, and ζ and Rev1-in an error-free or error-prone manner. Regarding the NBA adducts, namely, 2-(2-deoxyguanosin--yl)-3-aminobenzanthrone (dG--ABA) and -(2-deoxyguanosin-8-yl)-3-aminobenzanthrone (dG-C8-ABA), dG--ABA is produced more often than dG-C8-ABA, whereas dG-C8-ABA blocks DNA replication more strongly than dG--ABA. dG--ABA allows for a less error-prone bypass than dG-C8-ABA does. Pol η and κ are stronger contributors to TLS over dG-C8-ABA, and Pol κ bypasses dG-C8-ABA in an error-prone manner. TLS efficiency and error-proneness are affected by the sequences surrounding the adduct, as demonstrated in our previous study on an ABP adduct, -(2-deoxyguanosine-8-yl)-4-aminobiphenyl (dG-C8-ABP). Elucidation of the general mechanisms determining efficiency, error-proneness, and the polymerases involved in TLS over various adducts is the next step in the research on TLS. These TLS studies will clarify the mechanisms underlying aryl hydrocarbon mutagenesis and carcinogenesis in more detail.
PubMed: 29071010
DOI: 10.5487/TR.2017.33.4.265 -
Cold Spring Harbor Perspectives in... Apr 2011Classical secretion consists of the delivery of transmembrane and soluble proteins to the plasma membrane and the extracellular medium, respectively, and is mediated by... (Review)
Review
Classical secretion consists of the delivery of transmembrane and soluble proteins to the plasma membrane and the extracellular medium, respectively, and is mediated by the organelles of the secretory pathway, the Endoplasmic Reticulum (ER), the ER exit sites, and the Golgi, as described by the Nobel Prize winner George Palade (Palade 1975). At the center of this transport route, the Golgi stack has a major role in modifying, processing, sorting, and dispatching newly synthesized proteins to their final destinations. More recently, however, it has become clear that an increasing number of transmembrane proteins reach the plasma membrane unconventionally, either by exiting the ER in non-COPII vesicles or by bypassing the Golgi. Here, we discuss the evidence for Golgi bypass and the possible physiological benefits of it. Intriguingly, at least during Drosophila development, Golgi bypass seems to be mediated by a Golgi protein, dGRASP, which is found ectopically localized to the plasma membrane.
Topics: Biological Transport; Cell Membrane; Gene Expression Regulation; Golgi Apparatus; Proteins
PubMed: 21441587
DOI: 10.1101/cshperspect.a005298