Joachim Seybold

Moraxella catarrhalis is internalized in respiratory epithelial cells by a trigger-like mechanism and initiates a TLR2- and partly NOD1-dependent inflammatory immune response

Moraxella catarrhalis is an important pathogen in patients with chronic obstructive lung disease (COPD). While M.u2003catarrhalis has been categorized as an extracellular bacterium so far, the potential to invade human respiratory epithelium has not yet been explored. Our results obtained by electron and confocal microscopy demonstrated a considerable potential of M.u2003catarrhalis to invade bronchial epithelial (BEAS‐2B) cells, type II pneumocytes (A549) and primary small airway epithelial cells (SAEC). Moraxella invasion was dependent on cellular microfilament as well as on bacterial viability, and characterized by macropinocytosis leading to the formation of lamellipodia and engulfment of the invading organism into macropinosomes, thus indicating a trigger‐like uptake mechanism. In addition, the cells examined expressed TLR2 as well as NOD1, a recently found cytosolic protein implicated in the intracellular recognition of bacterial cell wall components. Importantly, inhibition of TLR2 or NOD1 expression by RNAi significantly reduced the M.u2003catarrhalis‐induced IL‐8 secretion. The role of TLR2 and NOD1 was further confirmed by overexpression assays in HEK293 cells. Overall, M.u2003catarrhalis may employ lung epithelial cell invasion to colonize and to infect the respiratory tract, nonetheless, the bacteria are recognized by cell surface TLR2 and the intracellular surveillance molecule NOD1.

Omalizumab decreased IgE-release and induced changes in cellular immunity in patients with allergic asthma

Background:u2002 Omalizumab, a recombinant monoclonal anti‐immunoglobulin E (IgE) antibody, shows proven efficacy in the treatment of allergic diseases. A little is known about the immunological pathways affected by the decrease of circulating free IgE during omalizumab treatment.

Adhesion of Moraxella catarrhalis to human bronchial epithelium characterized by a novel fluorescence-based assay

Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. Adhesion of this pathogen to epithelial cells is critical for its pathogenicity. Although much work has been done on identifying surface molecules of M. catarrhalis as adhesins, several adhesion assays were used in these studies which has never been validated or compared to each other. In the present study, we have examined the capacity of M. catarrhalis to adhere to different human epithelial cells. By using the two most commonly used adhesion assays based on the enumeration of colony-forming units or on the counting of adherent bacteria per epithelial cell by light microscopy, we identified significant limitations of both methods. These arose either from differences in strain-specific adhesion pattern on the epithelial cell surface or the dependence on the state of confluence of the epithelial cell layer. We developed a new fluorescence-based adhesion assay and compared our results to the two conventional methods. We demonstrated that the fluorescence-based adhesion assay offers a reliable and convenient method for the quantification of M. catarrhalis adhesion to confluent epithelial cell monolayers.

Combination of Structural MRI and FDG-PET of the Brain Improves Diagnostic Accuracy in Newly Manifested Cognitive Impairment in Geriatric Inpatients.

BACKGROUNDnThe cause of cognitive impairment in acutely hospitalized geriatric patients is often unclear. The diagnostic process is challenging but important in order to treat potentially life-threatening etiologies or identify underlying neurodegenerative disease.nnnOBJECTIVEnTo evaluate the add-on diagnostic value of structural and metabolic neuroimaging in newly manifested cognitive impairment in elderly geriatric inpatients.nnnMETHODSnEighty-one inpatients (55 females, 81.6±5.5 y) without history of cognitive complaints prior to hospitalization were recruited in 10 acute geriatrics clinics. Primary inclusion criterion was a clinical hypothesis of Alzheimers disease (AD), cerebrovascular disease (CVD), or mixed AD+CVD etiology (MD), which remained uncertain after standard diagnostic workup. Additional procedures performed after enrollment included detailed neuropsychological testing and structural MRI and FDG-PET of the brain. An interdisciplinary expert team established the most probable etiologic diagnosis (non-neurodegenerative, AD, CVD, or MD) integrating all available data. Automatic multimodal classification based on Random Undersampling Boosting was used for rater-independent assessment of the complementary contribution of the additional diagnostic procedures to the etiologic diagnosis.nnnRESULTSnAutomatic 4-class classification based on all diagnostic routine standard procedures combined reproduced the etiologic expert diagnosis in 31% of the patients (pu200a=u200a0.100, chance level 25%). Highest accuracy by a single modality was achieved by MRI or FDG-PET (both 45%, p≤0.001). Integration of all modalities resulted in 76% accuracy (p≤0.001).nnnCONCLUSIONnThese results indicate substantial improvement of diagnostic accuracy in uncertain de novo cognitive impairment in acutely hospitalized geriatric patients with the integration of structural MRI and brain FDG-PET into the diagnostic process.

Self-reported adverse reactions in 4337 healthcare workers immunizations against novel H1N1 influenza

PurposeThe use of the 2009 H1N1 vaccine has generated much debate concerning safety issues among the general population and physicians. It was questioned if this is a safe vaccine. Therefore, we investigated the safety of an inactivated monovalent H1N1 pandemic influenza vaccineMethodsWe focused on the H1N1 pandemic influenza vaccine Pandemrix® and applied a self reporting questionnaire in a population of healthcare workers (HCWs) and medical students at a major university hospital.ResultsIn total, 4337 individuals were vaccinated, consisting of 3808 HCWs and 529 medical students. The vaccination rate of the employees was higher than 40%. The majority of individuals were vaccinated in November 2009. In total, 291 of the 4337 vaccinations were reported to lead to one or more adverse reactions (6.7%). Local reactions were reported in 3.8%, myalgia and arthralgia in 3.7%, fatigue in 3.7%, headache in 3.1%.ConclusionsOur data together with available data from several national and international institutions points to a safe pandemic influenza vaccine.

Preserved brain metabolic activity at the age of 96 years.

Loss of brain tissue becomes notable to cerebral magnetic resonance imaging (MRI) at age 30 years, and progresses more rapidly from mid 60s. The incidence of dementia increases exponentially with age, and is all too frequent in the oldest old (≥ 90 years of age), the fastest growing age group in many countries. However, brain pathology and cognitive decline are not inevitable, even at extremely old age (den Dunnen et al., 2008).