Clinical and translational science
-
Mechanisms of hematopoietic failure in patients with aplastic anemia (AA) are obscure. We investigate alterations in the hematopoietic microenvironment in AA patients. We present the results of studying mesenchymal stromal cells (MSC), fibroblastic colony-forming units (CFU-F), and adherent cell layers (ACL) of long-term bone marrow cultures (LTBMC) from bone marrow (BM) samples of AA patients. ⋯ Addition of AA patients' serum to donors' LTBMC for 3 weeks induced similar gene expression alterations. The addition of parathyroid hormone (PTH) resulted in the expression levels of analyzed genes returning to normal, in both AA LTBMC and donor cultures treated with AA serum. The physiologic status of the BM stromal microenvironment (MSC, CFU-F, and ACL of LTBMC) of AA patients was altered.
-
Acute kidney injury (AKI) is associated with high morbidity and mortality. The lack of sensitive and specific injury biomarkers has greatly impeded the development of therapeutic strategies to improve outcomes of AKI. The unique objective of this study was to evaluate the diagnostic performance of nine urinary biomarkers of AKI-kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), hepatocyte growth factor (HGF), cystatin C (Cys), N-acetyl-beta-D-glucosaminidase (NAG), vascular endothelial growth factor (VEGF), chemokine interferon-inducible protein 10 (IP-10; CXCL10), and total protein-in a cross-sectional comparison of 204 patients with or without AKI. ⋯ The area under the receiver operating characteristics curve (AUC-ROC) for the combination of biomarkers using a logic regression model [risk score of 2.93*(NGAL > 5.72 and HGF > 0.17) + 2.93*(PROTEIN > 0.22) -2*(KIM < 0.58)] was greater (0.94) than individual biomarker AUC-ROCs. Age-adjusted levels of urinary KIM-1, NAG, HGF, VEGF, and total protein were significantly higher in patients who died or required renal replacement therapy (RRT) when compared to those who survived and did not require RRT. Our results demonstrate the comparative value of multiple biomarkers in the diagnosis and prognosis of AKI.
-
The dogma that the heart is a static organ which contains an irreplaceable population of cardiomyocytes prevailed in the cardiovascular field for the last several decades. However, the recent identification of progenitor cells that give rise to differentiated myocytes has prompted a re-interpretation of cardiac biology. The heart cannot be viewed any longer as a postmitotic organ characterized by a predetermined number of myocytes that is defined at birth and is preserved throughout life. ⋯ The regenerative ability of the heart was initially documented with a classic morphometric approach and more recently with the demonstration that DNA synthesis, mitosis, and cytokinesis take place in the newly formed myocytes of the normal and pathologic heart. Importantly, replicating myocytes correspond to the differentiated progeny of cardiac stem cells. These findings point to the possibility of novel therapeutic strategies for the diseased heart.