Increased airway smooth muscle (ASM) contractility and the development of airway hyperresponsiveness (AHR) are cardinal features of asthma, but the signaling pathways that promote these changes are poorly understood. Tyrosine phosphorylation is tightly regulated by the opposing actions of protein tyrosine kinases and phosphatases, but little is known about whether tyrosine phosphatases influence AHR. Here, we demonstrate that genetic inactivation of receptor-like protein tyrosine phosphatase J (Ptprj), which encodes CD148, protected mice from the development of increased AHR in two different asthma models. Surprisingly, CD148 deficiency minimally affected the inflammatory response to allergen, but significantly altered baseline pulmonary resistance. Mice specifically lacking CD148 in smooth muscle had decreased AHR, and the frequency of calcium oscillations in CD148-deficient ASM was substantially attenuated, suggesting that signaling pathway alterations may underlie ASM contractility. Biochemical analysis of CD148-deficient ASM revealed hyperphosphorylation of the C-terminal inhibitory tyrosine of SRC family kinases (SFKs), implicating CD148 as a critical positive regulator of SFK signaling in ASM. The effect of CD148 deficiency on ASM contractility could be mimicked by treatment of both mouse trachea and human bronchi with specific SFK inhibitors. Our studies identify CD148 and the SFKs it regulates in ASM as potential targets for the treatment of AHR.
Purpose Labour epidural analgesia (LEA) is an evolving field. Various neuraxial techniques and dosing regimens are available to the modern obstetric anesthesia provider, allowing for significant practice variability. To begin a search for consensus on optimal care, we sought to query fellowship training practices for LEA. Methods We conducted an electronic survey of institutions with American Council for Graduate Medical Education-accredited obstetric anesthesiology fellowship programs. We studied the frequency of epidural initiation techniques, including combined spinal epidural (CSE), dural puncture epidural, and epidural bolus. For maintenance techniques, we appraised the use of continuous epidural infusion, programmed intermittent bolus (PIEB), and patient-controlled epidural analgesia (PCEA). Results Of 40 institutions surveyed, we received 32 responses (80% response rate). Twenty-eight of 40 (70%) were included in the analysis. A plurality of institutions (12/28; 43%) preferred CSE, and among those who used
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