In chronic pancreatitis, increased concentrations of Na+ and Cl- in sweat have been attributed to increased parasympathetic drive. It was postulated that similar changes might occur in saliva. To avoid masking increased parasympathetic drive, saliva was collected without stimulation. In patients with chronic pancreatitis, there were significant increases of concentrations of Na+ and Cl- in basal salivary concentrations. These differences disappeared when salivary secretion was stimulated with citric acid. Anatomic or neurologic modification of the salivary glands seemed unlikely as stimulated concentrations did not differ from those in the control subjects. Perfusion of cholecystokinin (CCK) did not modify concentrations of Na+ or Cl-. Parasympathetic blockade reduced salivary secretion in both patients and controls (p less than 0.001). As tubular absorption of Na+ and Cl- was constant and the volume of saliva was diminished, it followed that there was a reduction in Na+ and Cl- salivary output. As amylase secretion is under sympathetic control, atropine had little effect other than increasing the salivary amylase concentration. The secretory modifications observed with atropine were the same in both patients and control subjects, as the increased parasympathetic drive of the patients was blocked.
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J Clin Invest
October 2024
Perinatal Institute, Divisions of Neonatology, Perinatal and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Nat Commun
September 2024
Perinatal Institute, Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Combined deletion of the histone methyl transferases Prdm3 and Prdm16 in early lung endoderm causes perinatal lethality due to respiratory failure from loss of AT2 cells and the accumulation of partially differentiated AT1 cells. Combination of single-cell RNA-seq, bulk ATAC-seq, and CUT&RUN data demonstrate that PRDM3 and PRDM16 regulate chromatin accessibility at NKX2-1 transcriptional targets critical for perinatal AT2 cell differentiation and surfactant homeostasis.
View Article and Find Full Text PDFbioRxiv
December 2023
Perinatal Institute, Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Medical Center.
Differential chromatin accessibility accompanies and mediates transcriptional control of diverse cell fates and their differentiation during embryogenesis. While the critical role of NKX2-1 and its transcriptional targets in lung morphogenesis and pulmonary epithelial cell differentiation is increasingly known, mechanisms by which chromatin accessibility alters the epigenetic landscape and how NKX2-1 interacts with other co-activators required for alveolar epithelial cell differentiation and function are not well understood. Here, we demonstrate that the paired domain zinc finger transcriptional regulators PRDM3 and PRDM16 regulate chromatin accessibility to mediate cell differentiation decisions during lung morphogenesis.
View Article and Find Full Text PDFCell Stem Cell
September 2023
Center for Regenerative Medicine, Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address:
Durable reconstitution of the distal lung epithelium with pluripotent stem cell (PSC) derivatives, if realized, would represent a promising therapy for diseases that result from alveolar damage. Here, we differentiate murine PSCs into self-renewing lung epithelial progenitors able to engraft into the injured distal lung epithelium of immunocompetent, syngeneic mouse recipients. After transplantation, these progenitors mature in the distal lung, assuming the molecular phenotypes of alveolar type 2 (AT2) and type 1 (AT1) cells.
View Article and Find Full Text PDFFront Immunol
January 2023
Cystic Fibrosis Foundation, Bethesda, MD, United States.
Neutrophil extracellular traps contribute to lung injury in cystic fibrosis and asthma, but the mechanisms are poorly understood. We sought to understand the impact of human NETs on barrier function in primary human bronchial epithelial and a human airway epithelial cell line. We demonstrate that NETs disrupt airway epithelial barrier function by decreasing transepithelial electrical resistance and increasing paracellular flux, partially by NET-induced airway cell apoptosis.
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