Role of p38 mitogen-activated protein kinase in posttraumatic immunosuppression in mice.

Background: Patients with multiple injuries surviving the initial insult are highly susceptible to secondary pneumonia, frequently progressing into sepsis and multiorgan failure. However, the underlying mechanisms of posttraumatic immunosuppression are poorly understood. We hypothesized that dysregulated p38 mitogen-activated protein kinase (MAPK) signaling accounts for impaired lung protective immunity in a model of trauma/hemorrhage (T/H) and subsequent pneumococcal pneumonia in mice.

Cathepsin G and neutrophil elastase play critical and nonredundant roles in lung-protective immunity against Streptococcus pneumoniae in mice.

Neutrophil serine proteases cathepsin G (CG), neutrophil elastase (NE), and proteinase 3 (PR3) have recently been shown to contribute to killing of Streptococcus pneumoniae in vitro. However, their relevance in lung-protective immunity against different serotypes of S. pneumoniae in vivo has not been determined so far.

Acoustic events and "optophonic" cochlear responses induced by pulsed near-infrared laser.

Optical stimulation of neural tissue within the cochlea was described as a possible alternative to electrical stimulation. Most optical stimulation was performed with pulsed lasers operating with near-infrared (NIR) light and in thermal confinement. Under these conditions, the coexistence of laser-induced optoacoustic stimulation of the cochlea ("optophony") has not been analyzed yet.

Dendritic cell depletion and repopulation in the lung after irradiation and bone marrow transplantation in mice.

Dendritic cells (DCs) are essential for innate and adaptive immunity, but are purported to exhibit variable radiosensitivity in response to irradiation in various bone marrow transplantation (BMT) protocols. To address this controversy, we analyzed the magnitude of depletion and repopulation of both lung CD11b(pos) DC and CD103(pos) DC subsets in response to irradiation and BMT in a murine model. In our study, CD45.

Evaluation of biophotonic imaging to estimate bacterial burden in mice infected with highly virulent compared to less virulent Streptococcus pneumoniae serotypes.

Bioluminescence imaging is an innovative, noninvasive tool to analyze infectious disease progression under real-life conditions in small laboratory animals. However, the relevance of bioluminescence imaging to monitor invasive compared to noninvasive bacterial infections of the lung has not been examined so far. In the current study, we systematically evaluated the importance of bioluminescence imaging to monitor pneumococcal disease progression by correlating biophotonic signals with lung bacterial loads in two mouse strains (BALB/c, C57BL/6) infected with either self-glowing, bioluminescent serotype 19 Streptococcus pneumoniae causing focal pneumonia or serotype 2 S.

Importance of CXC chemokine receptor 2 in alveolar neutrophil and exudate macrophage recruitment in response to pneumococcal lung infection.

Sustained neutrophilic infiltration is known to contribute to organ damage, such as acute lung injury. CXC chemokine receptor 2 (CXCR2) is the major receptor regulating inflammatory neutrophil recruitment in acute and chronic inflamed tissues. Whether or not the abundant neutrophil recruitment observed in severe pneumonia is essential for protective immunity against Streptococcus pneumoniae infections is incompletely defined.

Efficacy profiles of daptomycin for treatment of invasive and noninvasive pulmonary infections with Streptococcus pneumoniae.

Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e.

Important role for CC chemokine ligand 2-dependent lung mononuclear phagocyte recruitment to inhibit sepsis in mice infected with Streptococcus pneumoniae.

The monocyte chemoattractant CCL2 is of major importance in inflammatory monocyte recruitment to the lungs in response to bacterial infection. Streptococcus pneumoniae is the most prevalent pathogen in community-acquired pneumonia causing significant morbidity and mortality worldwide. In the current study, we examined the role of CCL2 in lung-protective immunity against two strains of S.

Overexpression of cathepsin K in mice decreases collagen deposition and lung resistance in response to bleomycin-induced pulmonary fibrosis.

Background: Lung fibrosis is a devastating pulmonary disorder characterized by alveolar epithelial injury, extracellular matrix deposition and scar tissue formation. Due to its potent collagenolytic activity, cathepsin K, a lysosomal cysteine protease is an interesting target molecule with therapeutic potential to attenuate bleomycin-induced pulmonary fibrosis in mice. We here tested the hypothesis that over-expression of cathepsin K in the lungs of mice is protective in bleomycin-induced pulmonary fibrosis.

FMS-like tyrosine kinase 3 ligand aggravates the lung inflammatory response to Streptococcus pneumoniae infection in mice: role of dendritic cells.

Pretreatment of mice with the hemopoietic growth factor, FMS-like tyrosine kinase 3 ligand (Flt3L), has been shown to increase monocyte-derived myeloid dendritic cells (DC) in lung parenchymal tissue, with possible implications for protective immunity to lung bacterial infections. However, whether Flt3L treatment improves lung innate immunity of mice to challenge with Streptococcus pneumoniae has not been investigated previously. Mice pretreated with Flt3L exhibited a peripheral monocytosis and a strongly expanded lung myeloid DC pool, but responded with a similar proinflammatory cytokine release (TNF-alpha, IL-6, keratinocyte derived cytokine, MIP-2, CCL2) and neutrophilic alveolitis upon infection with S.

Macrophage Turnover Kinetics in the Lungs of Mice Infected with Streptococcus pneumoniae.

Streptococcus pneumoniae is the most prevalent cause of community-acquired pneumonia and is known to induce apoptosis and necrosis in macrophages in vivo. We analyzed the kinetics of alveolar and lung parenchymal macrophage replacement by newly recruited exudate macrophages in vehicle-treated and S. pneumoniae-challenged bone marrow chimeric CD45.

Lung-specific overexpression of CC chemokine ligand (CCL) 2 enhances the host defense to Streptococcus pneumoniae infection in mice: role of the CCL2-CCR2 axis.

Mononuclear phagocytes are critical components of the innate host defense of the lung to inhaled bacterial pathogens. The monocyte chemotactic protein CCL2 plays a pivotal role in inflammatory mononuclear phagocyte recruitment. In this study, we tested the hypothesis that increased CCL2-dependent mononuclear phagocyte recruitment would improve lung innate host defense to infection with Streptococcus pneumoniae.

Importance of phosphoinositide 3-kinase gamma in the host defense against pneumococcal infection.

Rationale: The pivotal role of phosphoinositide 3-kinase gamma (PI3Kgamma) in leukocyte recruitment makes it an attractive target for immunomodulatory therapy. However, interfering with PI3Kgamma signaling might increase the risk of bacterial infections in humans.

Objectives: We hypothesized that deletion or pharmacologic inhibition of PI3Kgamma would impair the lung inflammatory response to the prototypic gram-positive bacterial pathogen Streptococcus pneumoniae.

Mediator responses of alveolar macrophages and kinetics of mononuclear phagocyte subset recruitment during acute primary and secondary mycobacterial infections in the lungs of mice.

Little is known about the activation programme induced in alveolar macrophages upon phagocytosis of mycobacteria and the concomitant mononuclear phagocyte migratory responses that shape the acute phase of mycobacterial infection. Using high-speed cell sorting in conjunction with real-time RT-PCR analysis, we show that sorted alveolar macrophages of transgenic CX3CR1+/GFP mice infected with red fluorescent-labelled Mycobacterium bovis BCG exhibited weak transcriptional changes of lysosomal cathepsins B, L, D, K and S, whereas antimicrobial cathepsin G was strongly induced upon infection. Moreover, mRNA levels of pattern recognition receptors TLR2, TLR4 and NOD2 were downregulated as were neutrophil chemoattractants KC, MIP-2 and IP-10, whereas highly upregulated mRNA levels of the monocyte chemoattractant CCL2 were observed.

Nanoparticle-based diagnosis and therapy.

Nanoparticles are at the leading edge of the rapidly developing field of material science in nanotechnology with many potential applications in clinical medicine and research. Due to their unique size-dependent properties nanoparticles offer the possibility to develop both new therapeutic and diagnostic tools. The ability to incorporate drugs into nanosystems displays a new paradigm in pharmacotherapy that could be used for cell-targeted drug delivery.

Resident alveolar macrophages are replaced by recruited monocytes in response to endotoxin-induced lung inflammation.

In the acute respiratory distress syndrome, recruitment of peripheral blood monocytes results in expansion of the total pool of resident alveolar macrophages. The fate of resident macrophages, or whether recruited monocytes are selectively eliminated from the alveolar airspace or differentiate into resident alveolar macrophages during the resolving phase of inflammation, has not been determined. Here, we analyzed the kinetics of resident and recruited macrophage turnover within the alveolar airspace of untreated and LPS-challenged mice.

Distribution of surfactant proteins in type II pneumocytes of newborn, 14-day old, and adult rats: an immunoelectron microscopic and stereological study.

Surfactant proteins (SP) have an important impact on the function of the pulmonary surfactant. In contrast to humans, rat lungs are immature at birth. Alveolarization starts on postnatal day 4.

Vertebral osteomyelitis and endocarditis of a pacemaker lead due to Granulicatella (Abiotrophia) adiacens.

Systemic infection due to Granulicatella (formerly Abiotrophia), a species of nutrition-deficient gram-positive cocci, is rare. We present the case of a 68-year-old diabetic male who presented with back pain and a history of fever and chills. Imaging studies revealed vertebral osteomyelitis of the Th 10/11 region.

Nephrotoxicity of selective COX-2 inhibitors.

We describe 2 male patients, a 49-year-old with psoriatic arthritis and impaired renal function and a 43-year-old renal transplant recipient, who both sustained a marked decline in glomerular filtration rate in conjunction with a selective inhibitor of cyclooxygenase-2 (COX-2), rofecoxib. In the second patient, acute renal failure necessitated hemodialysis. Both patients made an uneventful recovery.

Regulation of the proto-oncogenes c-sis, c-fos, c-myc and c-myb in acute myeloid leukemias.

RNA transcriptional levels of the proto-oncogenes c-sis, c-fos, c-myb and c-myc were measured in peripheral blood leukemic blast cells of 16 patients with acute myeloid leukemia (AML) of different FAB subtypes, 8 being at diagnosis and 8 upon relapse. The studied proto-oncogenes were found to be regulated but varied considerably within morphologically identical subtypes. This is consistent with the clinically observable diverse behavior of seemingly identical AMLs as to the course and outcome of the individual disease.

Immunodetection of a tumor associated antigen (TAG-12): comparison of microwave accelerated and conventional method.

The microwave stimulated immunodetection of a tumor associated antigen (TAG-12) by monoclonal antibody 7A9 and an avidinbiotinylated alkaline phosphatase kit was compared with the conventional staining method. No difference in the staining pattern of antibody 7A9 was noticed in serial paraffin sections of 50 specimens including normal, benign and malignant breast tissues after microwave irradiated and conventional immunostaining. The results demonstrate that microwave stimulated immunostaining gives reliable results and can remarkably reduce the time of the staining procedure.

Nutritional consequences of total gastrectomy: the relationship between mode of reconstruction, postprandial symptoms, and body composition.

Body composition, postprandial symptoms, and social performance were assessed in 41 patients who were free of tumors 16 to 63 months (median, 41 months) after total gastrectomy with Roux-en-Y esophagojejunostomy (n = 15) or jejunal interposition (n = 26). There were no significant differences with respect to age, sex, initial tumor stage, interval since operation, and premorbid weight/height2 (body mass index). The lowest postoperative body mass index (BMI) was 72% +/- 3% of the preillness BMI in patients with Roux-en-Y reconstruction and 79% +/- 2% in patients with jejunal interposition (p less than 0.

Magnetic resonance imaging (MRI) and high resolution computertomography (HRCT) in cochlear implant candidates.

Cochlear implant candidates must be thoroughly tested for their suitability pre-operatively. Electrical and electrophysiological tests as well as a psychological assessment are of fundamental importance in the selection process. The implantation of an intracochlear electrode requires specific information about the anatomy of the petrous bone and the endocochlear space.

Prevention of stress bleeding with ranitidine or pirenzepine and the risk of pneumonia.

In a prospective, controlled, randomized trial of stress bleeding prophylaxis, 400 patients in a surgical intensive care unit received 50 mg pirenzepine (n = 200) or 200 mg ranitidine (n = 200) daily. The drugs were administered continuously via an intravenous line. The mean duration of the treatment was 3.