The tryptic FAD-peptide carrying the flavin in 8alpha-(N3)histidyl linkage as natural hapten was isolated by HPLC from the bacterial enzyme 6-hydroxy-d-nicotine oxidase. The same flavin protein linkage is found in the mitochondrial succinate dehydrogenase flavoprotein subunit, the predominant flavoprotein with covalently bound FAD in mitochondria of cardiomyocytes. Peripheral blood mononuclear cells (PBMC) were isolated from four patients with acute myocarditis, seven patients with dilated cardiomyopathy (DCM) and from four healthy control individuals. The response of PBMC to the FAD-peptide was evaluated by measuring proliferation ([3H]-dThd incorporation) and cytokine secretion [interferon (IFN)-gamma]. PBMC from all patients with acute myocarditis showed positive responses to the FAD-peptide, in contrast to PBMC from patients with DCM or control individuals. Following the recovery of the patients from the acute inflammation of the heart, PBMC no longer exhibited a proliferation response to the FAD-peptide. A chemically synthesized FAD-free peptide with identical amino acid sequence induced no response of PBMC. The results are consistent with a recall response by activated T cells, specific for the normally cryptic mitochondrial flavin-hapten, which may be liberated following cardiomyocyte destruction during the inflammation of the heart.
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http://dx.doi.org/10.1046/j.1365-2249.2003.02130.x | DOI Listing |
Heart Fail Rev
January 2025
Department of Anesthesiology and Critical Care, Université Paris Cité, Paris, France.
Heart failure (HF), a chronic and progressive disease, is increasing in prevalence worldwide and is associated with increased hospitalizations and death. Despite notable improvements in medical therapy for HF, patients are still at risk of future negative outcomes. Current guidelines recommend four classes of medication for treating patients with HF, deemed guideline-directed medical therapy (GDMT).
View Article and Find Full Text PDFInt J Cardiovasc Imaging
January 2025
Department of Clinical Radiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, Greece.
The term acute aortic syndrome (AAS) refers to a range of different entities, including dissection, intramural haematoma and penetrating atherosclerotic ulcer. Patients with chronic renal disease and particularly those with dominant polycystic kidney disease are susceptible to this pathology, given the underlying renal arteriopathy and hypertension. Imaging plays a crucial role in diagnosing, grading and guiding management of these patients, with computed tomography angiography (CTA) being on the frontline.
View Article and Find Full Text PDFEur J Clin Pharmacol
January 2025
Department of the Acute Pain Service, St. Luke's University Health Network, 801 Ostrum St, Bethlehem, PA, 18015, USA.
Purpose: Opioid medications remain a common treatment for acute pain in hospitalized patients. This study aims to identify factors contributing to opioid overdose in the inpatient population, addressing the gap in data on which patients are at higher risk for opioid-related adverse events in the hospital setting.
Methods: A retrospective chart review of inpatients receiving at least one opioid medication was performed at a large academic medical center from January 1, 2022, through December 31, 2022.
Leukemia
January 2025
Australian Centre for Blood Diseases (ACBD), School of Translational Medicine, Monash University, Melbourne, VIC, Australia.
Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) is an immature subtype of T-cell acute lymphoblastic leukemia (T-ALL) commonly show deregulation of the LMO2-LYL1 stem cell transcription factors, activating mutations of cytokine receptor signaling, and poor early response to intensive chemotherapy. Previously, studies of the Lmo2 transgenic mouse model of ETP-ALL identified a population of stem-like T-cell progenitors with long-term self-renewal capacity and intrinsic chemotherapy resistance linked to cellular quiescence. Here, analyses of Lmo2 transgenic mice, patient-derived xenografts, and single-cell RNA-sequencing data from primary ETP-ALL identified a rare subpopulation of leukemic stem cells expressing high levels of the cytokine receptor FLT3.
View Article and Find Full Text PDFAnn Hematol
January 2025
Department of Hematology, Kanghua Hospital, Dongguan, Guangdong, P.R. China.
The efficacy and safety of total marrow irradiation (TMI) plus a reduced dose of melphalan as autologous stem cell transplantation (ASCT) preconditioning for multiple myeloma (MM) patients were evaluated. The 11 patients with MM had a median age of 57 (range: 46-75) years; six of them were at standard risk and five of them were at high risk based on the Mayo Stratification of Myeloma and Risk-adapted Therapy (mSMART) standard risk factors. Before ASCT, three patients achieved stringent complete response (sCR), two patients achieved complete remission (CR), and the rest of the patients had either partial response (PR) or progressive disease.
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