University of Texas Southwestern Medical Center

About: University of Texas Southwestern Medical Center is a healthcare organization based out in Dallas, Texas, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 39107 authors who have published 75242 publications receiving 4497256 citations. The organization is also known as: UT Southwestern & UT Southwestern Medical School.

Phosphoinositide regulation of the actin cytoskeleton.

Abstract: Phosphoinositides [PPIs, which collectively refer to phosphorylated derivatives of phosphatidylinositol (PI)] have a pivotal role as precursors to important second messengers and as bona fide signaling and scaffold targeting molecules. This review focuses on recent advances that elucidate how PPIs, particularly PI(4,5)P2 (PIP2), directly regulate the actin cytoskeleton in vivo by modulating the activity and targeting of actin regulatory proteins. The role of PIP2 in stimulating actin polymerization and in establishing cytoskeleton-plasma membrane linkages is emphasized. In addition, the review presents tantalizing evidence that suggests how binding of selected cytoskeletal proteins to membrane PPIs may promote PPI clustering into raft lipid microdomains, alter their accessibility to other proteins, and even distort the bilayer conformation. These actions have profound implications for many other PPI-regulated membrane functions that are beginning to be uncovered, and they suggest how PPIs can mediate crosstalk between the actin cytoskeleton and an expanding spectrum of essential cellular functions.

Epidemiology and Clinical Characteristics of Community-Acquired Pneumonia in Hospitalized Children

Abstract: Objectives. The precise epidemiology of childhood pneumonia remains poorly defined. Accurate and prompt etiologic diagnosis is limited by inadequate clinical, radiologic, and laboratory diagnostic methods. The objective of this study was to determine as precisely as possible the epidemiology and morbidity of community-acquired pneumonia in hospitalized children. Methods. Consecutive immunocompetent children hospitalized with radiographically confirmed lower respiratory infections (LRIs) were evaluated prospectively from January 1999 through March 2000. Positive blood or pleural fluid cultures or pneumolysin-based polymerase chain reaction assays, viral direct fluorescent antibody tests, or viral, mycoplasmal, or chlamydial serologic tests were considered indicative of infection by those organisms. Methods for diagnosis of pneumococcal pneumonia among study subjects were published by us previously. Selected clinical characteristics, indices of inflammation (white blood cell and differential counts and procalcitonin values), and clinical outcome measures (time to defervescence and duration of oxygen supplementation and hospitalization) were compared among groups of children. Results. One hundred fifty-four hospitalized children with LRIs were enrolled. Median age was 33 months (range: 2 months to 17 years). A pathogen was identified in 79% of children. Typical respiratory bacteria were identified in 60% (of which 73% were Streptococcus pneumoniae), viruses in 45%, Mycoplasma pneumoniae in 14%, Chlamydia pneumoniae in 9%, and mixed bacterial/viral infections in 23%. Preschool-aged children had as many episodes of atypical bacterial LRIs as older children. Children with typical bacterial or mixed bacterial/viral infections had the greatest inflammation and disease severity. Multivariate logistic-regression analyses revealed that high temperature (≥38.4°C) within 72 hours after admission (odds ratio: 2.2; 95% confidence interval: 1.4–3.5) and the presence of pleural effusion (odds ratio: 6.6; 95% confidence interval: 2.1–21.2) were significantly associated with bacterial pneumonia. Conclusions. This study used an expanded diagnostic armamentarium to define the broad spectrum of pathogens that cause pneumonia in hospitalized children. The data confirm the importance of S pneumoniae and the frequent occurrence of bacterial and viral coinfections in children with pneumonia. These findings will facilitate age-appropriate antibiotic selection and future evaluation of the clinical effectiveness of the pneumococcal conjugate vaccine as well as other candidate vaccines.

Evasion of intracellular host defence by hepatitis C virus

Abstract: Viral infection of mammalian cells rapidly triggers intracellular signalling events leading to interferon alpha/beta production and a cellular antiviral state. This 'host response' is our first line of immune defence against infection as it imposes several barriers to viral replication and spread. Hepatitis C virus (HCV) evades the host response through a complex combination of processes that include signalling interference, effector modulation and continual viral genetic variation. These evasion strategies support persistent infection and the spread of HCV. Defining the molecular mechanisms by which HCV regulates the host response is of crucial importance and may reveal targets for novel therapeutic strategies.