CSP7 Protects Alveolar Epithelial Cells by Targeting -Fibrinolytic Pathways During Lung Injuries.

Impaired alveolar epithelial regeneration in patients with idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) is attributed to telomere dysfunction in type II alveolar epithelial cells (ACs). Genetic susceptibility, aging, and toxicant exposures, including tobacco smoke (TS), contribute to telomere dysfunction in ACs. Here we investigated whether improvement of telomere function plays a role in CSP7-mediated protection of ACs against ongoing senescence and apoptosis during bleomycin (BLM)-induced pulmonary fibrosis (PF) as well as alveolar injury caused by chronic TS exposure.

Defective expansion and function of memory like natural killer cells in HIV+ individuals with latent tuberculosis infection.

Purpose: Tuberculosis (TB) is the leading cause of infectious disease related mortality, and only 10% of the infected individuals develop active disease. The likelihood of progression of latent tuberculosis infection (LTBI) to active TB disease is high in HIV infected individuals. Identification of HIV+ individuals at risk would allow treating targeted population, facilitating completion of therapy for LTBI and prevention of TB development.

Improving T-cell assays for diagnosis of latent TB infection: Confirmation of the potential role of testing Interleukin-2 release in Iranian patients.

Background: Since gamma interferon release assays (IGRAs) cannot differentiate between active tuberculosis and latent tuberculosis infection (LTBI), development of rapid and specific diagnosis tools are essential for discriminating between active tuberculosis (TB) from LTBI. Both IGRAs are based on Mycobacterium tuberculosis-specific antigens, namely, early secretory antigenic target 6 (ESAT-6) and 10kDa culture filtrate (CFP-10). The aim of this study was to evaluate the potential value of IL-2 secretion by whole blood cells after stimulation with rESAT-6 and rCFP-10 for discriminating between active and latent tuberculosis.

RNase HI Is Essential for Survival of Mycobacterium smegmatis.

RNases H are involved in the removal of RNA from RNA/DNA hybrids. Type I RNases H are thought to recognize and cleave the RNA/DNA duplex when at least four ribonucleotides are present. Here we investigated the importance of RNase H type I encoding genes for model organism Mycobacterium smegmatis.

Calmodulin-like protein from M. tuberculosis H37Rv is required during infection.

M. tuberculosis constitutes very sophisticated signaling systems that convert the environment signals into appropriate cellular response and helps the bacilli to overcome the onslaught of host defence mechanisms. Although mycobacterial two-component systems and STPKs have gained lot of attention as virulence factors, mycobacterial calcium signaling has not been very well studied.

Multidrug-resistant tuberculosis. Recommendations for reducing risk during travel for healthcare and humanitarian work.

Healthcare and humanitarian workers who travel to work where the incidence of multidrug-resistant tuberculosis (MDR TB) is high and potential transmission may occur are at risk of infection and disease due to these resistant strains. Transmission occurs due to inadequate transmission control practices and the inability to provide timely and accurate diagnosis and treatment of persons with MDR TB. Patients risk exposure if active TB is unrecognized in workers after they return to lower-risk settings.

Thyroid transcription factor-1 (TTF-1) gene: identification of ZBP-89, Sp1, and TTF-1 sites in the promoter and regulation by TNF-α in lung epithelial cells.

Thyroid transcription factor-1 (TTF-1/Nkx2.1/TITF1) is a homeodomain-containing transcription factor essential for the morphogenesis and differentiation of the lung. In the lung, TTF-1 controls the expression of surfactant proteins that are essential for lung stability and lung host defense.

Induction of tissue factor by urokinase in lung epithelial cells and in the lungs.

Rationale: Urokinase-type plasminogen activator (uPA) regulates extracellular proteolysis in lung injury and repair. Although alveolar expression of uPA increases, procoagulant activity predominates.

Objectives: This study was designed to investigate whether uPA alters the expression of tissue factor (TF), the major initiator of the coagulation cascade, in lung epithelial cells (ECs).

The two-domain LysX protein of Mycobacterium tuberculosis is required for production of lysinylated phosphatidylglycerol and resistance to cationic antimicrobial peptides.

The well-recognized phospholipids (PLs) of Mycobacterium tuberculosis (Mtb) include several acidic species such as phosphatidylglycerol (PG), cardiolipin, phosphatidylinositol and its mannoside derivatives, in addition to a single basic species, phosphatidylethanolamine. Here we demonstrate that an additional basic PL, lysinylated PG (L-PG), is a component of the PLs of Mtb H37Rv and that the lysX gene encoding the two-domain lysyl-transferase (mprF)-lysyl-tRNA synthetase (lysU) protein is responsible for L-PG production. The Mtb lysX mutant is sensitive to cationic antibiotics and peptides, shows increased association with lysosome-associated membrane protein-positive vesicles, and it exhibits altered membrane potential compared to wild type.

Enzyme kinetics and characterization of mouse pancreatic elastase.

In the present study we have purified and characterized murine pancreatic elastase. The enzyme was extracted from acetone powders of mouse pancreas, fractionally precipitated with ammonium sulfate, and further purified by ion exchange chromatography to a single band on SDS-PAGE. The mouse enzyme exists in a proform, which was activated by removing a signal peptide by tryptic cleavage.

Post-transcriptional regulation of urokinase-type plasminogen activator receptor expression in lipopolysaccharide-induced acute lung injury.

Rationale: Urokinase-type plasminogen activator (uPA) receptor (uPAR) is required for the recruitment of neutrophils in response to infection. uPA induces its own expression in lung epithelial cells, which involves its interaction with cell surface uPAR. Regulation of uPAR expression is therefore crucial for uPA-mediated signaling in infectious acute lung injury (ALI).

Factor VIIa interaction with tissue factor and endothelial cell protein C receptor on cell surfaces.

Factor VIIa (FVIIa) is the enzyme that triggers activation of the clotting cascade that eventually leads to fibrin deposition and platelet activation. Association of FVIIa with its cellular receptor, tissue factor (TF), which greatly increases FVIIa enzymatic activity, is essential for the effective initiation of the coagulation pathway. FVIIa also complexes with endothelial cell protein C receptor (EPCR), but this association does not increase the enzymatic activity of FVIIa.

Characterization of effector functions of human peptide-specific CD4+ T-cell clones for an intracellular pathogen.

CD4+ T cells are believed to play a dominant role in human defenses against Mycobacterium tuberculosis through production of interferon (IFN)-gamma, cytolytic T-cell (CTL) activity, and inhibition of intracellular mycobacterial growth. Most functional studies of CD4+ cells have used bulk T-cells that recognize crude mycobacterial antigens, and the functional capacity of individual human T cells is not well defined. We studied the functional capacity of human CD4+ T-cell clones that recognize a specific mycobacterial peptide.

Triptolide inhibits interferon-gamma-induced programmed death-1-ligand 1 surface expression in breast cancer cells.

Triptolide, a natural compound purified from the Chinese herb Tripterygium wilfordii, has been reported to inhibit the growth and metastasis of tumors in vivo. However, the effects of triptolide on the immune responses of cancer cells remain unknown. Up-regulation of programmed death-1-ligand 1 (PD-L1) in cancer cells is an important mechanism of tumor immune evasion.

Posttranscriptional regulation of urokinase receptor expression by heterogeneous nuclear ribonuclear protein C.

Interaction of urokinase-type plasminogen activator (uPA) with its receptor, uPAR, is a key regulatory step in uPA-mediated cell proliferation and migration. Our previous studies demonstrated that posttranscriptional stabilization of uPAR mRNA by uPA contributes to the induction of cell surface uPAR expression, and heterogeneous nuclear ribonuclear protein C1 (hnRNPC) binds to a 110 nt sequence of uPAR mRNA 3'-UTR, thereby preventing its degradation. These observations indicate that hnRNPC could be involved in the induction of uPAR expression by uPA.

Histone deacetylase inhibitors: mechanisms and clinical significance in cancer: HDAC inhibitor-induced apoptosis.

Epigenic modifications, mainly DNA methylation and acetylation, are recognized as the main mechanisms contributing to the malignant phenotype. Acetylation and deacetylation are catalyzed by specific enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. While histones represent a primary target for the physiological function of HDACs, the antitumor effect of HDAC inhibitors might also be attributed to transcription-independent mechanisms by modulating the acetylation status of a series of non-histone proteins.

Racial differences in diabetes self-management and quality of care in Texas.

Aim: To assess racial/ethnic differences in diabetes self-management behaviors and quality of care in Texas.

Methods: This cross-sectional study assessed self-management behaviors and quality of care in 1720 adults with diabetes in the 2002-2004 Texas Behavioral Risk Factor Surveillance Survey. Multiple logistic regression models were used for assessing the independent association between race/ethnicity, self-management behaviors, and quality of care variables controlling for covariates.

Urokinase expression by tumor suppressor protein p53: a novel role in mRNA turnover.

Lung carcinoma (H1299) cells deficient in p53 (p53(-/-)) express large amounts of urokinase-type plasminogen activator (uPA) protein and uPA mRNA, and exhibit slower degradation of uPA mRNA than that of p53-expressing nonmalignant Beas2B human airway epithelial cells. Expression of p53 protein in H1299 cells, upon transfection with p53 cDNA, suppressed basal as well as uPA-induced expression of uPA protein in both conditioned media and cell lysates, and decreased the level of steady-state uPA mRNA primarily due to increased uPA mRNA turnover. Inhibition of p53 expression by RNA silencing (SiRNA) in Beas2B cells enhanced basal and uPA-mediated uPA protein and mRNA expression with stabilization of uPA mRNA.

Faith-based intervention in depression, anxiety, and other mental disturbances.

Objective: To determine if the effects of using the Steps to Freedom would be beneficial for a group of individuals who attended a Christian Conference.

Methods: A user-friendly 12-item questionnaire was used to monitor the outcomes of Steps to Freedom addressing six symptom/behavioral problems and six function areas. In addition, the Symptom Checklist-90 R (SCL-90-R) questionnaire was employed to document the validity of the shorter questionnaire.

Medicolegal issues in pathology.

The various methods used by risk managers to assist clinicians in handling medicolegal risk, including improving communication with patients and better dealing with medical records issues, are not particularly of benefit to pathologists. An understanding of tort law, the theory of negligence, the principle of standard of care, and the role of the expert witness helps the pathologist generally assess and manage risk and put it into context with daily pathology practice. An understanding of the litigation process and techniques to better handle a deposition and high-risk specimens or diagnoses are of practical value in avoiding a lawsuit or increasing the likelihood for good outcome in medical malpractice litigation.

If a picture is worth a thousand words, what is a trauma computerized tomography panel worth?

Background: There has been a progressive increase in the use of computerized tomography (CT) scans for evaluating trauma patients. The purpose of this study was to quantify that trend and consider the implications it holds for resource use.

Methods: Data were combined from the trauma registry and the radiology department's administrative information system at a level I trauma center to define the radiographic use patterns applied to all trauma activations during a 3-month sampling period in each of 4 years.

Angiotensin II directly triggers endothelial exocytosis via protein kinase C-dependent protein kinase D2 activation.

Angiotensin II (AII) has been reported to induce leukocyte adhesion to endothelium through up-regulation of P-selectin surface expression. However, the underlying molecular and cellular mechanisms remain unknown. P-selectin is stored in Weibel-Palade bodies (WPBs), large secretory granules, in endothelial cells.

Granulocyte-macrophage colony stimulating factor-mediated innate responses in tuberculosis.

The mechanisms by which GM-CSF mediates bacterial clearance and inflammation during mycobacterial infection are poorly understood. The objective of this work was to determine how GM-CSF alters pulmonary mycobacterial infection in vivo. Differences in GM-CSF levels in the lungs of normal mice (GM(+/+)), transgenic GM-CSF-deficient (GM-CSF(-/-)), and transgenic mice with high GM-CSF expression only in lung epithelial cells (SP-C-GM-CSF(+/+)/GM(-/-)) did not affect pulmonary infection rates caused by either the attenuated Mycobacterium bovis BCG or the virulent Mycobacterium tuberculosis H37Rv.