The lung collectin surfactant protein A (SP-A) has been implicated in the regulation of pulmonary host defense and inflammation. Zymosan induces proinflammatory cytokines in immune cells. Toll-like receptor (TLR)2 has been shown to be involved in zymosan-induced signaling. We first investigated the interaction of TLR2 with zymosan. Zymosan cosedimented the soluble form of rTLR2 possessing the putative extracellular domain (sTLR2). sTLR2 directly bound to zymosan with an apparent binding constant of 48 nM. We next examined whether SP-A modulated zymosan-induced cellular responses. SP-A significantly attenuated zymosan-induced TNF-α secretion in RAW264.7 cells and alveolar macrophages in a concentration-dependent manner. Although zymosan failed to cosediment SP-A, SP-A significantly reduced zymosan-elicited NF-κB activation in TLR2-transfected human embryonic kidney 293 cells. Because we have shown that SP-A binds to sTLR2, we also examined whether SP-A affected the binding of sTLR2 to zymosan. SP-A significantly attenuated the direct binding of sTLR2 to zymosan in a concentration-dependent fashion. From these results, we conclude that 1) TLR2 directly binds zymosan, 2) SP-A can alter zymosan-TLR2 interaction, and 3) SP-A down-regulates TLR2-mediated signaling and TNF-α secretion stimulated by zymosan. This study supports an important role of SP-A in controlling pulmonary inflammation caused by microbial pathogens.
Pulmonary surfactant proteins (SP) A and D play important roles in the innate immune system of the lung. These proteins belong to the collectin subgroup in which lectin domains are associated with collagenous structures. To obtain a better understanding of how lung collectins modulate cellular responses, the authors investigated whether SP-A interacts with the toll-like receptor 2 (TLR2). SP-A bound to TLR2 and inhibited interactions between TLR2 and TLR2-ligands such as peptidoglycan (PGN) and zymosan. NF-κ B activation and tumour necrosis factor-α expression induced by PGN or zymosan were significantly inhibited in the presence of SP-A. Lung collectins may act as inhibitors of lung inflammation in respiratory infections. The authors also examined the effects of lung collectins on the phagocytosis of bacteria by alveolar macrophages. Lung collectins enhanced the uptake of S. pneumoniae or M. avium by alveolar macrophages. It was demonstrated that the direct interaction of lung collectins with macrophages resulted in increased cell surface expression of scavenger receptor A or mannose receptor, which are responsible for phagocytosis. This study has emphasized the biological relevance of SP-A and SP-D against various respiratory infections, however, a more complete understanding of the molecular mechanism is required.
Objective: To evaluate whether proper diagnoses were made at an emergency department to elderly patients who presented with abdominal pain, and to identify factors associated with acute surgical condition. Methods: A two-year retrospective review of patients aged 65 years and older complaining of abdominal pain who presented to the emergency department. Results: 189 patients were enrolled. The over all accuracy rate for emergency department diagnoses was 79%. Of the 13 (7.1%) patients with a very different diagnosis from the first diagnosis after admission, six cases were not initially recognized as an acute surgical condition, and surgery was delayed. Factors associated with acute surgical condition by univariate analyses included tachypnea, hypothermia, persistent pain, perspiration, hyperglycemia, hypoalbuminemia, hypocalcemia, and the presence of systemic inflammatory response syndrome. A multivariate, logistic regression analysis indicates that persistent pain is a possible predictive factor indicating an acute surgical condition. In all six cases where such a condition initially went unrecognized, the abdominal CT was a key resource in revealing an acute surgical condition. Conclusions: In the emergency department, diagnosis of abdominal pain in the elderly with less specific symptoms is difficult and less accurate. Persistent pain is a possible predictive factor indicating an acute surgical condition and patients with persistent pain should be evaluated by abdominal CT scan early in the evaluative process.
Background and objectives: The optimal mode of treatment in spontaneous supratentorial intracerebral hemorrhage (SICH) is controversial. We assessed the value of hematoma evacuation in SICH in a case-control study. Methods: One hundred and forty-five patients with SICH without tumor or vascular abnormalities. Indication for surgery were made upon admission in 11 and after clinical deterioration in 13 patients. Assessed were age, sex. Glasgow Coma Scale (GCS), pupillary reaction on admission, localisation, etiology and hematoma volume, presence of ventricular blood, and Glasgow Outcome Scale on discharge. From further analysis patients > 80 years or with hematoma volume < 10 ml were excluded. Statistical analysis included: (i) a multiple regression model to determine prognostic factors; (ii) comparison between medical and surgical patients; (iii) matching the 24 evacuated with 24 medical patients according to those parameters retained from the regression model and additionally to other suspected factors influencing outcome; (iv) comparison between both groups to confirm comparability; and (v) testing for different outcome between the groups. Results: Prognostic factors were GCS, hematoma volume and location. All 24 evacuated patients could be matched to a medically treated patient regarding age, hematoma volume and location. GCS and pupillary reaction. Differences between both groups could not be detected. Outcome was not different between the medical and surgical group. Conclusions: Hematoma evacuation does not improve outcome in supratentorial spontaneous hemorrhages. Since mainly deteriorating patients were evacuated, the only effect of hematoma evacuation may be to stop deterioration rather than to improve overall outcome. P002 Is 'brain swelling' a clinical particular kind of severe brain injury?
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.