Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite-induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions
BackgroundThiamine (vitamin B1) is an essential molecule for all life forms because thiamine diphosphate (ThDP) is an indispensable cofactor for oxidative energy metabolism. The less abundant thiamine monophosphate (ThMP), thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP), present in many organisms, may have still unidentified physiological functions. Diseases linked to thiamine deficiency (polyneuritis, Wernicke-Korsakoff syndrome) remain frequent among alcohol abusers and other risk populations. This is the first comprehensive study on the distribution of thiamine derivatives in human biopsies, body fluids and cell lines.Methodology and Principal FindingsThiamine derivatives were determined by HPLC. In human tissues, the total thiamine content is lower than in other animal species. ThDP is the major thiamine compound and tissue levels decrease at high age. In semen, ThDP content correlates with the concentration of spermatozoa but not with their motility. The proportion of ThTP is higher in humans than in rodents, probably because of a lower 25-kDa ThTPase activity. The expression and activity of this enzyme seems to correlate with the degree of cell differentiation. ThTP was present in nearly all brain and muscle samples and in ∼60% of other tissue samples, in particular fetal tissue and cultured cells. A low ([ThTP]+[ThMP])/([Thiamine]+[ThMP]) ratio was found in cardiovascular tissues of patients with cardiac insufficiency. AThTP was detected only sporadically in adult tissues but was found more consistently in fetal tissues and cell lines.Conclusions and SignificanceThe high sensitivity of humans to thiamine deficiency is probably linked to low circulating thiamine concentrations and low ThDP tissue contents. ThTP levels are relatively high in many human tissues, as a result of low expression of the 25-kDa ThTPase. Another novel finding is the presence of ThTP and AThTP in poorly differentiated fast-growing cells, suggesting a hitherto unsuspected link between these compounds and cell division or differentiation.
E Ev va al lu ua at ti io on n o of f t th he e s so ol li it ta ar ry y p pu ul lm mo on na ar ry y n no od du ul le e b by y p po os si it tr ro on n e em mi is ss si io on n t to om mo og gr ra ap ph hy y i im ma ag gi in ng g We performed a prospective study of 50 patients referred to the Pneumology Department with unclear diagnoses of SPN after conventional radiological screening. PET study was performed on each subject before an invasive procedure was proposed.Thirty three patients had a malignant nodule and 17 had a benign nodule. The mean size of malignant nodule was 3 cm (range 1.5-4.5 cm). All showed a marked increase in 18-FDG uptake. The mean size of benign nodule was 1.8 cm (range 0.5-3.5 cm). PET imaging showed the absence of 18-FDG uptake and correctly identified 15 of 17 benign nodules. There were two false-positive cases with a moderate increase in 18-FDG uptake (1 postprimary tuberculosis; and 1 anthracosilicotic nodule with nonspecific inflammation). At present, the sensitivity and specificity of the method are 100 and 88%, respectively. The positive and negative predictive values of PET imaging for SPNs are 94 and 100%, respectively.Our preliminary results demonstrate that PET-FDG imaging is a noninvasive technique, which appears highly accurate in differentiating malignant SPN from benign SPN.
In this preliminary report we have investigated the ability of FDG-PET to differBackground -Positron emission tomography (PET) with 18-fluorodeoxyglucose entiate between malignant and non-malignant pleural disease. (FDG) is an accurate method for differentiating benign from malignant disease. The use of FDG-PET for the aetiological diagnosis of pleural disease was in-Methods vestigated in 25 patients. Methods -PET was performed on each Twenty five subjects of mean age 60 years subject before invasive procedures were (range 36-80) undergoing evaluation of pleural used to determine the aetiological dia-disease were enrolled in the study. Each subject gnosis. The PET data were analysed by was examined by chest radiography, CT scanvisual interpretation of coronal, sagittal, ning (PQ 2000 4th generation, Picker, Cleveand transverse slices.land, Ohio, USA) and pleural fluid analysis. A Results -Sixteen patients were found to PET study was performed on each subject have malignant pleural disease and nine before invasive procedures were carried out. had benign disease. All patients with histologically confirmed malignant disease showed FDG uptake within the pleural thickening which was intense in 14 cases PET was performed with an UGM Penn PET and moderate in two. PET imaging showed 240H scanner as previously described 4 and the the absence of FDG uptake and correctly data were analysed by visual interpretation of categorised seven non-malignant lesions. coronal, sagittal, and transverse slices alone Two patients with infectious pleural dis-and by cross referencing. PET images were eases showed a localised and moderate read independently by two nuclear physicians, FDG uptake.who had knowledge of the standard chest radioConclusion -Our preliminary results sug-graph only, by evaluation of the presence or gest that FDG-PET could be an effective absence of 18 FDG uptake in the pleural space. tool for differentiating between benign and When increased 18 FDG uptake was observed, malignant pleural diseases.two levels were identified -moderate or intense.
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