University of Louisville

About: University of Louisville is a education organization based out in Louisville, Kentucky, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 24600 authors who have published 49248 publications receiving 1573346 citations. The organization is also known as: UofL.

Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivo

Abstract: Stroking of the skin produces pleasant sensations that can occur during social interactions with conspecifics, such as grooming Despite numerous physiological studies (reviewed in ref 2), molecularly defined sensory neurons that detect pleasant stroking of hairy skin in vivo have not been reported Previously, we identified a rare population of unmyelinated sensory neurons in mice that express the G-protein-coupled receptor MRGPRB4 These neurons exclusively innervate hairy skin with large terminal arborizations that resemble the receptive fields of C-tactile (CT) afferents in humans Unlike other molecularly defined mechanosensory C-fibre subtypes, MRGPRB4^+ neurons could not be detectably activated by sensory stimulation of the skin ex vivo Therefore, we developed a preparation for calcium imaging in the spinal projections of these neurons during stimulation of the periphery in intact mice Here we show that MRGPRB4^+ neurons are activated by massage-like stroking of hairy skin, but not by noxious punctate mechanical stimulation By contrast, a different population of C fibres expressing MRGPRD was activated by pinching but not by stroking, consistent with previous physiological and behavioural data Pharmacogenetic activation of Mrgprb4-expressing neurons in freely behaving mice promoted conditioned place preference, indicating that such activation is positively reinforcing and/or anxiolytic These data open the way to understanding the function of MRGPRB4 neurons during natural behaviours, and provide a general approach to the functional characterization of genetically identified subsets of somatosensory neurons in vivo

Transgenic Overexpression of Constitutively Active Protein Kinase C ε Causes Concentric Cardiac Hypertrophy

Abstract: —To test the hypothesis that activation of the protein kinase C (PKC) e isoform leads to cardiac hypertrophy without failure, we studied transgenic mice with cardiac-specific overexpression...

Integrin α2β1 mediates outside-in regulation of platelet spreading on collagen through activation of Src kinases and PLCγ2

Abstract: Collagen plays a critical role in hemostasis by promoting adhesion and activation of platelets at sites of vessel injury. In the present model of platelet–collagen interaction, adhesion is mediated via the inside-out regulation of integrin α2β1 and activation through the glycoprotein VI (GPVI)–Fc receptor (FcR) γ-chain complex. The present study extends this model by demonstrating that engagement of α2β1 by an integrin-specific sequence from within collagen or by collagen itself generates tyrosine kinase–based intracellular signals that lead to formation of filopodia and lamellipodia in the absence of the GPVI–FcR γ-chain complex. The same events do not occur in platelet suspensions. α2β1 activation of adherent platelets stimulates tyrosine phosphorylation of many of the proteins in the GPVI–FcR γ-chain cascade, including Src, Syk, SLP-76, and PLCγ2 as well as plasma membrane calcium ATPase and focal adhesion kinase. α2β1-mediated spreading is dramatically inhibited in the presence of the Src kinase inhibitor PP2 and in PLCγ2-deficient platelets. Spreading is abolished by chelation of intracellular Ca2+. Demonstration that adhesion of platelets to collagen via α2β1 generates intracellular signals provides a new insight into the mechanisms that control thrombus formation and may explain the unstable nature of β1-deficient thrombi and why loss of the GPVI–FcR γ-chain complex has a relatively minor effect on bleeding.

Early Switch From Intravenous to Oral Antibiotics and Early Hospital Discharge A Prospective Observational Study of 200 Consecutive Patients With Community-Acquired Pneumonia

Abstract: Objectives: To determine the proportion of patients who can be treated with early switch to oral antibiotics and early discharge, to evaluate clinical outcome and patient satisfaction for patients treated with early switch and early discharge, and to define the factors that interfere with early discharge for some of the patients who underwent early switch to oral antibiotic therapy. Design: Prospective study. Participants: Two hundred consecutive hospitalized patients with community-acquired pneumonia. Main Outcome Measures: Number of days needed to switch to oral therapy and length of hospital stay. Clinical outcome and satisfaction with care were evaluated for those patients treated with early switch and early discharge. Results: Early switch to oral antibiotics (within the first 3 days of hospitalization) was performed in 133 patients (67%). Clinical failure was documented in 1 patient. Early switch and early discharge was performed in 88 patients (44%). The mean length of hospital stay for this group was 3.4 days. The most common reason for prolonged hospitalization after the switch to oral antibiotics was the need for diagnostic workup. More than 95% of patients were satisfied with the care they had received. Conclusions: Using simple clinical and laboratory criteria, a significant proportion of hospitalized patients with community-acquired pneumonia (44%) can be treated with early switch and early discharge. This model did not affect patient outcome, decreased the length of hospitalization, and was associated with a high level of patient satisfaction. Arch Intern Med. 1999;159:2449-2454