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Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.
J Med Chem
January 2025
Ma̅tai Ha̅ora - Centre for Redox Biology and Medicine, Department of Biomedical Science and Pathology, University of Otago, Christchurch, Christchurch 8140, New Zealand.
In humans, the 2-oxoglutarate-dependent dioxygenases (2-OGDDs) catalyze hydroxylation reactions involved in cell metabolism, the biosynthesis of small molecules, DNA and RNA demethylation, the hypoxic response and the formation of collagen. The reaction is catalyzed by a highly oxidizing ferryl-oxo species produced when the active site non-heme iron engages molecular oxygen. Enzyme activity is specifically stimulated by l-ascorbic acid (ascorbate, vitamin C), an effect not well mimicked by other reducing agents.
View Article and Find Full Text PDFSolitary Plasmacytoma: Single institution experience and systematic review and meta-analysis of clinical outcomes.
Blood Adv
January 2025
Mayo Clinic, Rochester, Minnesota, United States.
In this study, we first analyzed data from 147 patients with solitary plasmacytomas treated at the Mayo Clinic between 2005 and 2022 and then expanded our investigation through a systematic review and meta-analysis of 62 studies, encompassing 3,487 patients from the years 1960 to 2022. Our findings reveal that patients with up to 10% clonal plasma cells in their bone marrow (BM), denoted as plasmacytoma +, had a significantly reduced median disease-free survival (DFS) of 15.7 months vs.
View Article and Find Full Text PDFChimeric antigen receptor (CAR) T-cell products axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel) are approved for relapsed/refractory large B-cell lymphoma (R/R LBCL). Emerging evidence indicates that delayed CAR T-cell infusion, including prolonged time from leukapheresis to infusion, known as vein-to-vein time (V2Vt), may adversely impact clinical outcomes. We conducted a systematic literature review (SLR) and meta-analysis to identify differences in V2Vt in patients with R/R LBCL treated with axi-cel, tisa-cel, or liso-cel.
View Article and Find Full Text PDFSerial Total Bile Acid Measurements in Intrahepatic Cholestasis of Pregnancy.
Obstet Gynecol
January 2025
Department of Obstetrics, Gynecology and Reproductive Science, University of California, San Diego, San Diego, California; and the Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai Health System & Icahn School of Medicine at Mount Sinai, New York, and the Department of Obstetrics, Gynecology and Reproductive Science, New York City Health and Hospitals - Elmhurst Hospital Center, Elmhurst, New York.
Although peak serum total bile acid (TBA) levels guide management of intrahepatic cholestasis of pregnancy (ICP), whether ICP progresses in severity and when or how to assess bile acid levels serially remains unclear. We conducted a secondary analysis of a single-institution retrospective cohort study to assess bile acid trends across pregnancy among individuals diagnosed with ICP and to evaluate whether there was progression to higher ICP severity. We defined ICP severity as mild (peak TBA less than 40 micromol/L), moderate (peak TBA between 40 and 100 micromol/L), or severe (peak TBA 100 micromol/L or greater).
View Article and Find Full Text PDFMRD-guided zanubrutinib, venetoclax and obinutuzumab in relapsed CLL: primary endpoint analysis from the CLL2-BZAG trial.
Blood
January 2025
Department I of Internal Medicine and German CLL Study Group; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD); University of Cologne, Faculty of Medicine and University Hos, Cologne, Germany.
The phase 2 CLL2-BZAG trial tested a measurable residual disease (MRD)-guided combination treatment of zanubrutinib, venetoclax and obinutuzumab after an optional bendamustine debulking in patients with relapsed/refractory CLL. In total, 42 patients were enrolled and two patients with ≤2 induction cycles were excluded from the analysis population per protocol. Patients had a median of one prior therapy (range 1-5), 18 patients (45%) had already received a BTK inhibitor (BTKi), seven patients (17.
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