416 research outputs found
Evolving gaps: Occupational structure in southern and northern Italy, 1400â1861
During the Risorgimento (1800â61), southern Italy was less
industrial than central-northern Italy and initially agricultural
provinces in the north saw rapid structural transformation.
During the Renaissance (1400â1600), structural
transformation in the south led to a near halving of the initial
difference in agricultural employment share between
the centre-north and the south, but convergence came to
a halt with the âseventeenth-century crisisâ. These trends
suggest that regional inequality was evolving rather than
persistent
Migratory marker expression in fibroblast foci of idiopathic pulmonary fibrosis
BACKGROUND: Fibroblast foci (FF) are considered a relevant morphologic marker of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), and are recognised as sites where fibrotic responses are initiated and/or perpetuated in this severe disease. Despite their relevance, the cellular and molecular mechanisms responsible for the formation of FF and their role in tissue remodelling are poorly defined. In previous studies we have provided evidence of abnormal activation of the wnt-signaling-pathway in IPF/UIP that is centred on FF and the overlying epithelium. This important morphogenetic pathway is able to trigger epithelial-mesenchymal-transition (EMT), a mechanism involved in developmental and metastatic processes, which is also potentially involved in pulmonary fibrosis. METHODS: Since EMT is characterised by enhancement of migratory potential of cells, we investigated the molecular profile of FF in 30 biopsies of IPF/UIP and a variety of control samples, focussing on the immunohistochemical expression of three molecules involved in cell motility and invasiveness, namely laminin-5-Îł2-chain, fascin, and heat-shock-protein-27. RESULTS: We provide evidence that in UIP these three molecules are abnormally expressed in discrete clusters of bronchiolar basal cells precisely localised in FF. These cellular clusters expressed laminin-5-Îł2-chain and heat-shock-protein-27 at very high levels, forming characteristic three-layered lesions defined as "sandwich-foci" (SW-FF). Upon quantitative analysis SW-FF were present in 28/30 UIP samples, representing more than 50% of recognisable FF in 21/30, but were exceedingly rare in a wide variety of lung pathologies examined as controls. In UIP, SW-FF were often observed in areas of microscopic honeycombing, and were also found at the interface between normal lung tissue and areas of dense scarring. CONCLUSION: These molecular abnormalities strongly suggest that SW-FF represent the leading edge of pulmonary remodelling, where abnormal migration and re-epithelialisation take place, and that abnormal proliferation and migration of bronchiolar basal cells have a major role in the remodelling process characterising IPF/UIP. Further investigations will assess their possible use as reliable markers for better defining the UIP-pattern in difficult cases
The value of transbronchial lung biopsy using jumbo forceps via rigid bronchoscope in diffuse lung disease
Background. Transbronchial lung biopsy (TBLB) is a valuable procedure used to obtain a parenchymal specimen in the evaluation of diffuse lung infiltrates. Large forceps are expected to result in larger specimens and improve diagnostic yield. Aim. The objective of this study was to evaluate diagnostic yield of TBLB using large modified flexible gastroenterological forceps (âJumbo forcepsâ) compared with ânormalâ flexible forceps via rigid bronchoscopy in patients with diffuse parenchymal lung disease (DPLD). Methods. The study was a prospective analysis of 95 patients who underwent fluoroscopy guided TBLB over a two year period. Patients with a lung mass or solitary lung nodule undergoing TBLB were excluded. The larger and small forceps were used in a random sequence to avoid a reduction in diagnostic yield of the second series of biopsies related to possible bleeding by first series of biopsies. To minimize the consequence of haemorrhage, we performed every rigid bronchoscopy, placing a non inflated Fogarty balloon and a rigid aspirator (diameter 4 mm) in lobar bronchus near the biopsy segment. The Fogarty balloon has been inflated in case of bleeding. After the bleeding was controlled we continued to operate up to the biopsy segment. Results. Diagnostic yield of TBLB using Jumbo forceps was significantly higher than using normal flexible forceps via rigid bronchoscopy in patients with DPLD (p=0.001). In 74 out of 95 patients (78%) the diagnosis was placed with Jumbo forcep while the smaller forcep was diagnostic in 62 out of 95 patients (65%). Large forceps obtained significantly more tissue than the small forceps; the biopsy specimen taken with normal forcep measured in average 1.4 x 1.0 mm and the larger biopsy taken with jumbo forcep measured in average 2.5 x 1.9 mm (p < 0.005). Conclusion. The use of large biopsy forceps to perform TBLB via rigid bronchoscope can significantly increase diagnostic yield in the pathological diagnosis of diffuse infiltrative lung disease
Measurement of neutron capture on Ca at thermal and thermonuclear energies
At the Karlsruhe pulsed 3.75\,MV Van de Graaff accelerator the thermonuclear
Ca(n,)Ca(8.72\,min) cross section was measured by the
fast cyclic activation technique via the 3084.5\,keV -ray line of the
Ca-decay. Samples of CaCO enriched in Ca by 77.87\,\% were
irradiated between two gold foils which served as capture standards. The
capture cross-section was measured at the neutron energies 25, 151, 176, and
218\,keV, respectively. Additionally, the thermal capture cross-section was
measured at the reactor BR1 in Mol, Belgium, via the prompt and decay
-ray lines using the same target material. The
Ca(n,)Ca cross-section in the thermonuclear and thermal
energy range has been calculated using the direct-capture model combined with
folding potentials. The potential strengths are adjusted to the scattering
length and the binding energies of the final states in Ca. The small
coherent elastic cross section of Ca+n is explained through the nuclear
Ramsauer effect. Spectroscopic factors of Ca have been extracted from
the thermal capture cross-section with better accuracy than from a recent (d,p)
experiment. Within the uncertainties both results are in agreement. The
non-resonant thermal and thermonuclear experimental data for this reaction can
be reproduced using the direct-capture model. A possible interference with a
resonant contribution is discussed. The neutron spectroscopic factors of
Ca determined from shell-model calculations are compared with the values
extracted from the experimental cross sections for Ca(d,p)Ca and
Ca(n,)Ca.Comment: 15 pages (uses Revtex), 7 postscript figures (uses psfig), accepted
for publication in PRC, uuencoded tex-files and postscript-files also
available at ftp://is1.kph.tuwien.ac.at/pub/ohu/Ca.u
The value of transbronchial lung biopsy using jumbo forceps via rigid bronchoscope in diffuse lung disease.
Background. Transbronchial lung biopsy (TBLB) is a valuable procedure used to obtain a parenchymal specimen in the evaluation of diffuse lung infiltrates. Large forceps are expected to result in larger specimens and improve diagnostic yield. Aim. The objective of this study was to evaluate diagnostic yield of TBLB using large modified flexible gastroenterological forceps ("Jumbo forceps") compared with 'normal' flexible forceps via rigid bronchoscopy in patients with diffuse parenchymal lung disease (DPLD). Methods. The study was a prospective analysis of 95 patients who underwent fluoroscopy guided TBLB over a two year period. Patients with a lung mass or solitary lung nodule undergoing TBLB were excluded. The larger and small forceps were used in a random sequence to avoid a reduction in diagnostic yield of the second series of biopsies related to possible bleeding by first series of biopsies. To minimize the consequence of haemorrhage, we performed every rigid bronchoscopy, placing a non inflated Fogarty balloon and a rigid aspirator (diameter 4 mm) in lobar bronchus near the biopsy segment. The Fogarty balloon has been inflated in case of bleeding. After the bleeding was controlled we continued to operate up to the biopsy segment. Results. Diagnostic yield of TBLB using Jumbo forceps was significantly higher than using normal flexible forceps via rigid bronchoscopy in patients with DPLD (p=0.001). In 74 out of 95 patients (78%) the diagnosis was placed with Jumbo forcep while the smaller forcep was diagnostic in 62 out of 95 patients (65%). Large forceps obtained significantly more tissue than the small forceps; the biopsy specimen taken with normal forcep measured in average 1.4 x 1.0 mm and the larger biopsy taken with jumbo forcep measured in average 2.5 x 1.9 mm (p < 0.005). Conclusion. The use of large biopsy forceps to perform TBLB via rigid bronchoscope can significantly increase diagnostic yield in the pathological diagnosis of diffuse infiltrative lung disease
Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.
Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed
Fatal cytokine release syndrome by an aberrant FLIP/STAT3 axis
Inflammatory responses rapidly detect pathogen invasion and mount a regulated reaction. However, dysregulated anti-pathogen immune responses can provoke life-threatening inflammatory pathologies collectively known as cytokine release syndrome (CRS), exemplified by key clinical phenotypes unearthed during the SARS-CoV-2 pandemic. The underlying pathophysiology of CRS remains elusive. We found that FLIP, a protein that controls caspase-8 death pathways, was highly expressed in myeloid cells of COVID-19 lungs. FLIP controlled CRS by fueling a STAT3-dependent inflammatory program. Indeed, constitutive expression of a viral FLIP homolog in myeloid cells triggered a STAT3-linked, progressive, and fatal inflammatory syndrome in mice, characterized by elevated cytokine output, lymphopenia, lung injury, and multiple organ dysfunctions that mimicked human CRS. As STAT3-targeting approaches relieved inflammation, immune disorders, and organ failures in these mice, targeted intervention towards this pathway could suppress the lethal CRS inflammatory state
Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection.
Most cases of primary salivary mucosa-associated lymphoid tissue lymphoma are associated either with Sjoegren syndrome or hepatitis C virus infection
Comparison of Epithelial Differentiation and Immune Regulatory Properties of Mesenchymal Stromal Cells Derived from Human Lung and Bone Marrow
Mesenchymal stromal cells (MSCs) reside in many organs including lung, as shown by their isolation from fetal lung tissues, bronchial stromal compartment, bronchial-alveolar lavage and transplanted lung tissues. It is still controversial whether lung MSCs can undergo mesenchymal-to-epithelial-transition (MET) and possess immune regulatory properties. To this aim, we isolated, expanded and characterized MSCs from normal adult human lung (lung-hMSCs) and compared with human bone marrow-derived MSCs (BM-hMSCs). Our results show that lung-MSCs reside at the perivascular level and do not significantly differ from BM-hMSCs in terms of immunophenotype, stemness gene profile, mesodermal differentiation potential and modulation of T, B and NK cells. However, lung-hMSCs express higher basal level of the stemness-related marker nestin and show, following in vitro treatment with retinoic acid, higher epithelial cell polarization, which is anyway partial when compared to a control epithelial bronchial cell line. Although these results question the real capability of acquiring epithelial functions by MSCs and the feasibility of MSC-based therapeutic approaches to regenerate damaged lung tissues, the characterization of this lung-hMSC population may be useful to study the involvement of stromal cell compartment in lung diseases in which MET plays a role, such as in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis
- âŠ