Prolonged increases in fetal lung expansion stimulate fetal lung growth and development, but the effects on pulmonary hemodynamics are unknown. Our aim was to determine the effect of increased fetal lung expansion, induced by tracheal obstruction (TO), on pulmonary blood flow (PBF) and vascular resistance (PVR). Chronically catheterized fetal sheep (n = 6) underwent TO from 120 to 127 days of gestational age (term approximately 147 days); tracheas were not obstructed in control fetuses (n = 6). PBF, PVR, and changes to the PBF waveform were determined. TO significantly increased lung wet weight compared with control (166.3 +/- 20.2 vs. 102.0 +/- 18.8 g; P < 0.05). Despite the increase in intraluminal pressure caused by TO (5.0 +/- 0.9 vs. 2.4 +/- 1.0 mmHg; P < 0.001), PBF and PVR were similar between groups after 7 days (TO 28.1 +/- 3.2 vs. control 34.1 +/- 10.0 ml.min(-1).100 g lung wt(-1)). However, TO markedly altered pulmonary hemodynamics associated with accentuated fetal breathing movements, causing a reduction rather than an increase in PBF at 7 days of TO. To account for the increase in intraluminal pressure, the pressure was equalized by draining the lungs of liquid on day 7 of TO. Pressure equalization increased PBF from 36.8 +/- 5.2 to 112.4 +/- 22.8 ml/min (P = 0.01) and markedly altered the PBF waveform. These studies provide further evidence to indicate that intraluminal pressure is an important determinant of PBF and PVR in the fetus. We suggest that the increase in PBF associated with pressure equalization following TO reflects an increase in growth of the pulmonary vascular bed, leading to an increase in its cross-sectional area.
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Heart Lung
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Intermediate Care Unit, Department of Internal Medicine, Hospital Alto Vicentino (AULSS-7), Santorso, VI 36014, Italy.
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Translational Science and Therapeutics Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
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January 2025
Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Tissue-specific T cell immune responses play a critical role in maintaining organ health but can also drive immune pathology during both autoimmunity and alloimmunity. The mechanisms controlling intratissue T cell programming remain unclear. Here, we leveraged a nonhuman primate model of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation to probe the biological underpinnings of tissue-specific alloimmune disease using a comprehensive systems immunology approach including multiparameter flow cytometry, population-based transcriptional profiling, and multiplexed single-cell RNA sequencing and TCR sequencing.
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Department of Medical Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
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Cancer Res Commun
January 2025
University of Minnesota, Minnesota, MN, United States.
Neuroendocrine neoplasms (NENs) encompass a diverse set of malignancies with limited precision therapy options. Recently, therapies targeting DLL3 have shown clinical efficacy in aggressive NENs, including small cell lung cancers and neuroendocrine prostate cancers. Given the continued development and expansion of DLL3-targeted therapies, we sought to characterize the expression of DLL3 and identify its clinical and molecular correlates across diverse neuroendocrine and non-neuroendocrine cancers.
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