Identification of novel target genes in human lung tissue involved in chronic obstructive pulmonary disease.

Introduction: As part of a study aimed at illuminating at least some of the complex molecular events taking place in COPD, we screened tissues by means of transcriptome analyses.

Materials And Methods: Tissues were subjected to transcriptome analysis. Candidate genes were identified and validated by immunohistochemistry.

E-cigarettes and cigarettes worsen peripheral and central hemodynamics as well as arterial stiffness: A randomized, double-blinded pilot study.

The introduction of electronic cigarettes has led to widespread discussion on the cardiovascular risks compared to conventional smoking. We therefore conducted a randomized cross-over study of the acute use of three tobacco products, including a control group using a nicotine-free liquid. Fifteen active smokers were studied during and after smoking either a cigarette or an electronic cigarette with or without nicotine (eGo-T CE4 vaporizer).

Coupling killing to neutralization: combined therapy with ceftriaxone/Pep19-2.5 counteracts sepsis in rabbits.

Sepsis, which is induced by severe bacterial infections, is a major cause of death worldwide, and therapies combating the disease are urgently needed. Because many drugs have failed in clinical trials despite their efficacy in mouse models, the development of reliable animal models of sepsis is in great demand. Several studies have suggested that rabbits reflect sepsis-related symptoms more accurately than mice.

Long-term mortality and quality of life in intensive care patients treated for pneumonia and/or sepsis: Predictors of mortality and quality of life in patients with sepsis/pneumonia.

Purpose: The purpose of this study is to evaluate long-term mortality and quality of life (QoL) of intensive care patients with pneumonia and/or sepsis 1 year after discharge and to identify potential predictors for these outcome measures.

Methods: This retrospective cohort study analyzed all patients admitted to the intensive care unit (ICU) of a German university hospital with diagnosis of pneumonia and/or sepsis between 2008 and 2009. Quality of life was assessed by telephone interview or mail using the standardized EuroQol 5-dimension questionaire.

Nontypeable Haemophilus Influenzae Infection Upregulates the NLRP3 Inflammasome and Leads to Caspase-1-Dependent Secretion of Interleukin-1β - A Possible Pathway of Exacerbations in COPD.

Rationale: Nontypeable Haemophilus influenzae (NTHi) is the most common cause for bacterial exacerbations in chronic obstructive pulmonary disease (COPD). Recent investigations suggest the participation of the inflammasome in the pathomechanism of airway inflammation. The inflammasome is a cytosolic protein complex important for early inflammatory responses, by processing Interleukin-1β (IL-1β) to its active form.

Mortality in human sepsis is associated with downregulation of Toll-like receptor 2 and CD14 expression on blood monocytes.

Pattern recognition receptors are a key component of the first line host defense against infection, recognizing specific microbial products. We hypothesize that monocyte hyporesponsiveness in human sepsis is associated with a downregulation of the pattern recognition receptors Toll-like receptor (TLR)-2 and TLR4.Protein expression of CD14, TLR2 and TLR4 on blood monocytes was examined using flow cytometry from 29 patients with sepsis and 14 healthy controls.

Hospital acquired pneumonia with high-risk bacteria is associated with increased pulmonary matrix metalloproteinase activity.

Background: Neutrophil products like matrix metalloproteinases (MMP), involved in bacterial defence mechanisms, possibly induce lung damage and are elevated locally during hospital- acquired pneumonia (HAP). In HAP the virulence of bacterial species is known to be different. The aim of this study was to investigate the influence of high-risk bacteria like S.

Modulation of the inflammatory response to Streptococcus pneumoniae in a model of acute lung tissue infection.

Streptococcus pneumoniae is the leading pathogen of community-acquired pneumonia and is a main cause of infectious deaths. However, little is known about host-pathogen interaction in human lung tissue. We tested the hypothesis that human alveolar macrophages (AMs) and alveolar epithelial cells (AECs) are important for initiating the host response against S.

A novel human ex vivo model for the analysis of molecular events during lung cancer chemotherapy.

Background: Non-small cell lung cancer (NSCLC) causes most of cancer related deaths in humans and is characterized by poor prognosis regarding efficiency of chemotherapeutical treatment and long-term survival of the patients. The purpose of the present study was the development of a human ex vivo tissue culture model and the analysis of the effects of conventional chemotherapy, which then can serve as a tool to test new chemotherapeutical regimens in NSCLC.

Methods: In a short-term tissue culture model designated STST (Short-Term Stimulation of Tissues) in combination with the novel *HOPE-fixation and paraffin embedding method we examined the responsiveness of 41 human NSCLC tissue specimens to the individual cytotoxic drugs carboplatin, vinorelbine or gemcitabine.

Disparate innate immune responses to persistent and acute Chlamydia pneumoniae infection in chronic obstructive pulmonary disease.

Rationale: Chlamydia pneumoniae (Cpn) infection may play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Few data are available comparing persistent and acute infection of this pathogen in the human respiratory tract.

Objectives: To study Cpn-induced innate immune responses in lung tissue from patients with COPD and control subjects ex vivo and in vitro.

Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients.

Background: Cigarette smoke exposure including biologically active lipopolysaccharide (LPS) in the particulate phase of cigarette smoke induces activation of alveolar macrophages (AM) and alveolar epithelial cells leading to production of inflammatory mediators. This represents a crucial mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). Respiratory pathogens are a major cause of exacerbations leading to recurrent cycles of injury and repair.

Human lung cancer cells express functionally active Toll-like receptor 9.

Background: CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells.

Alveolar epithelial cells type II are major target cells for C. pneumoniae in chronic but not in acute respiratory infection.

Pulmonary presence of Chlamydia pneumoniae is associated with acute and chronic infections. We show that unapparent chlamydial infection in four out of 31 chronic obstructive pulmonary disease (COPD) patients (12.9%) is characterized by a significant increase in infected alveolar epithelial cells type II (18.

Toll-like receptor 2 is expressed by alveolar epithelial cells type II and macrophages in the human lung.

The ability of the host to recognize pulmonary invasion by pathogenic organisms and establish an appropriate host response to infection requires innate immune defense mechanisms. Early bacterial clearance in the lung is mediated by alveolar macrophages (AM) and polymorphonuclear neutrophils. Additionally alveolar epithelial cells type II (AEC-II) may act as immunoregulatory cells.