Single-Nucleotide Polymorphisms within the cps Loci: Another Potential Source of Clinically Important Genetic Variation for Streptococcus pneumoniae?

The Streptococcus pneumoniae capsule is essential for disease pathogenesis, suggesting that even minor genetic changes within the cps locus could potentially have important consequences. Arends et al. have identified 79 different non-synonymous SNPs in the cps locus of 338 19A serotype strains, and shown significant variations between strains in nucleotide sugars content and capsule shedding. Further work is required to characterise whether any of these changes have important functional consequences on capsule/host interactions

Improving Pulmonary Immunity to Bacterial Pathogens Through Streptococcus pneumoniae Colonisation of the Nasopharynx

Streptococcus pneumoniae is a common cause of bacterial pneumonia especially in the elderly or those with significant comorbidities, and is also frequently associated with exacerbations of COPD (1, 2). Existing S. pneumoniae vaccines have partial strain coverage, may lack efficacy in high risk groups, and generally seem to have poorer efficacy against pulmonary compared to systemic infection (3,4). Hence alternative strategies to conventional vaccines maybe required to prevent the persisting high morbidity and mortality caused by S. pneumoniae lung infections

Lung function, symptoms and inflammation during exacerbations of non-cystic fibrosis bronchiectasis: a prospective observational cohort study.

Exacerbations of non-cystic fibrosis bronchiectasis cause significant morbidity but there are few detailed data on their clinical course and associated physiological changes. The biology of an exacerbation has not been previously described

Management of community-acquired pneumonia: essential tips for the physician on call

Community-acquired pneumonia is a common clinical problem requiring admission to hospital, with a particularly high incidence in the elderly population and those with significant comorbidities. Diagnosis is made on the combination of a short history of respiratory symptoms and systemic ill-health with new examination and/or radiological features of consolidation. Multiple other infective and non-infective conditions can mimic community-acquired pneumonia, leading to misdiagnosis in 5–17% of cases. The CURB-65 score can identify patients with community-acquired pneumonia with a higher risk of mortality, but is insensitive at identifying patients requiring intensive care support and needs to be combined with clinical markers of potential severity. Both high admission levels of C-reactive protein and the failure of levels of C-reactive protein to decline by >50% by day 4 after admission are associated with higher risk of complications, need for ventilation or inotropic support, and mortality. Empirical antibiotic therapy for most patients admitted to hospital is combination of a ß-lactam and a macrolide. Short courses of antibiotics do not result in significantly different outcomes to longer courses unless the patient has developed complications such as a complex parapneumonic effusion. Implementation of a community-acquired pneumonia care bundle into clinical practice reduces mortality, and should be a high priority for all acute hospitals

Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channels

The relationship between receptor-induced membrane phosphatidylinositol-4'5'-bisphosphate (PIP2) hydrolysis and M-current inhibition was assessed in single-dissociated rat sympathetic neurons by simultaneous or parallel recording of membrane current and membrane-to-cytosol translocation of the fluorescent PIP2/inositol 1,4,5-trisphosphate (IP3)-binding peptide green fluorescent protein-tagged pleckstrin homology domain of phospholipase C (GFP-PLC delta-PH). The muscarinic receptor agonist oxotremorine-M produced parallel time- and concentration-dependent M-current inhibition and GFP-PLC delta-PH translocation; bradykinin also produced parallel time- dependent inhibition and translocation. Phosphatidylinositol-4-phosphate-5-kinase (PI5-K) overexpression reduced both M-current inhibition and GFP-PLC delta-PH translocation by both oxotremorine-M and bradykinin. These effects were partly reversed by wortmannin, which inhibits phosphatidylinositol-4-kinase (PI4-K). PI5-K overexpression also reduced the inhibitory action of oxotremorine-M on PIP2-gated G-protein-gated inward rectifier (Kir3.1/3.2) channels; bradykinin did not inhibit these channels. Overexpression of neuronal calcium sensor-1 protein (NCS-1), which increases PI4-K activity, did not affect responses to oxotremorine-M but reduced both fluorescence translocation and M-current inhibition by bradykinin. Using an intracellular IP3 membrane fluorescence-displacement assay, initial mean concentrations of membrane [PIP2] were estimated at 261 mu M (95% confidence limit; 192-381 mu M), rising to 693 mu M (417-1153 mu M) in neurons overexpressing PI5-K. Changes in membrane [PIP2] during application of oxotremorine-M were calculated from fluorescence data. The results, taken in conjunction with previous data for KCNQ2/3 (Kv7.2/Kv7.3) channel gating by PIP2 (Zhang et al., 2003), accorded with the hypothesis that the inhibitory action of oxotremorine-M on M current resulted from depletion of PIP2. The effects of bradykinin require additional components of action, which might involve IP3-induced Ca2+ release and consequent M-channel inhibition (as proposed previously) and stimulation of PIP2 synthesis by Ca2+-dependent activation of NCS-1

Gain curves in depletable food patches: A test of five models with European starlings

A forager's gain curve, the cumulative number of prey harvested from a patch as a function of time spent in the patch, influences optimal patch departure rules and interpretations of patch use data. We describe models of five different search strategies that yield different gain curves. Hence they would influence a forager's decision for patch departure differently and, consequently, how researchers should interpret patch residence times and giving-up densities. However, the models are virtually impossible to separate based on data of the gain curves per se. Therefore, we develop a series of diagnostic tests that can be used to discriminate among models. These tests consider how the instantaneous harvest rate within patches depends on initial (IPD) and current prey density (CPD) and search time. We applied these tests to data collected from European starlings (Sturnus vulgaris) foraging in experimental food patches of known initial prey density. The starlings' harvest rate increased with CPD, an indication of diminishing returns. However, a given CPD yielded a lower instantaneous intake rate the higher the IPD. Thus, the two models most commonly assumed in foraging studies, systematic and random search, can be unequivocally rejected. Instead, we found support for a new model, negative stirring, in which the starlings spoil their own future foraging returns by aggregating the remaining prey items as they search

Bacterial Infection Elicits Heat Shock Protein 72 Release from Pleural Mesothelial Cells

Heat shock protein 70 (HSP70) has been implicated in infection-related processes and has been found in body fluids during infection. This study aimed to determine whether pleural mesothelial cells release HSP70 in response to bacterial infection in vitro and in mouse models of serosal infection. In addition, the in vitro cytokine effects of the HSP70 isoform, Hsp72, on mesothelial cells were examined. Further, Hsp72 was measured in human pleural effusions and levels compared between non-infectious and infectious patients to determine the diagnostic accuracy of pleural fluid Hsp72 compared to traditional pleural fluid parameters. We showed that mesothelial release of Hsp72 was significantly raised when cells were treated with live and heat-killed Streptococcus pneumoniae. In mice, intraperitoneal injection of S. pneumoniae stimulated a 2-fold increase in Hsp72 levels in peritoneal lavage (p<0.01). Extracellular Hsp72 did not induce or inhibit mediator release from cultured mesothelial cells. Hsp72 levels were significantly higher in effusions of infectious origin compared to non-infectious effusions (p<0.05). The data establish that pleural mesothelial cells can release Hsp72 in response to bacterial infection and levels are raised in infectious pleural effusions. The biological role of HSP70 in pleural infection warrants exploration

Cytomegalovirus pneumonitis complicated by a central peribronchial pattern of organising pneumonia

We present five cases of cytomegalovirus (CMV) pneumonitis occurring in patients after recent T cell deplete allogeneic stem cell transplantation (AlloHSCT). These cases were complicated by an organising pneumonia (during the recovery period) with a predominantly central peribronchial pattern. All patients presented with evidence of active CMV pneumonitis which was treated successfully with anti-viral therapy but was followed by persistent severe dyspnoea, cough and hypoxia. High resolution computed tomography (HRCT) imaging showed widespread central peribronchial consolidation with traction bronchiectasis. There was a marked clinical and physiological improvement after treatment with systemic corticosteroids. However, in all patients the lung function remained abnormal and in some cases imaging revealed a fibrosing lung disease. These cases represent a previously undescribed central peribronchial pattern of organising pneumonia complicating CMV pneumonitis that can result in chronic lung damage