200 research outputs found
Italian national data bank of stillbirth vs. SIDS.
Sudden perinatal death, which includes antepartum
death (from 22 completed weeks of gestation), intrapartum
death and early neonatal death (occurring
within seven completed days of life), and sudden infant
death syndrome (SIDS), represents one of the major
sociomedical and scientific problems still lacking a
solution in today\u2019s medicine.1 However, little effort is
being made to find a cause of these deaths, as there is
no standard method of performing an autopsy in these
victims, and no database exists from which researchers
can draw autopsy results. Therefore, the need to submit
the young victims to necropsy procedures through a
standardized protocol is unanimously recognized, and
the chance of preventing perinatal unexpected death
and SIDS relies mainly on a better knowledge of the
underlying alterations of organs and etiopathogenetic
mechanisms. Similarly, for diagnostic purposes, an
accurate and careful examination of the circumstantial,
environmental, and familial situation within which the
death occurred is extremely important.
All the information related to victims of sudden
and unexplained fetal death and SIDS will soon be
made available in Italy through a specific data bank
established under the Law 31/2006 \u201cRegulations for
Diagnostic Post Mortem Investigation in Victims of
Sudden Infant Death Syndrome (SIDS) and Unexpected
Fetal Death.\u201d2 This law mandates that infants
who die suddenly within one year of life, and fetuses
that die after 22 weeks of gestation without any
apparent cause, must be rapidly submitted\u2014with the
consent of both parents\u2014to diagnostic postmortem
investigation.3 Information about the pregnancy, fetal
development and delivery, and, in the case of SIDS,
the environmental and familial situation in which the
death occurred\u2014in addition to information related
to risk factors\u2014must be collected by the obstetriciangynecologist,
neonatologist, pediatrician, and pathologist
involved in the case and recorded in the registry of
the data bank. In addition, to facilitate the collection
and analysis of the data, this data bank will allow the
Lino Rossi Research Center in collaboration with the
Epidemiology Center of the Italian National Health
Institute to update the population through public
education
and prevention programs aimed at decreasing
the incidence of stillbirth and SIDS
Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis
Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies
Clusters of galaxies : observational properties of the diffuse radio emission
Clusters of galaxies, as the largest virialized systems in the Universe, are
ideal laboratories to study the formation and evolution of cosmic
structures...(abridged)... Most of the detailed knowledge of galaxy clusters
has been obtained in recent years from the study of ICM through X-ray
Astronomy. At the same time, radio observations have proved that the ICM is
mixed with non-thermal components, i.e. highly relativistic particles and
large-scale magnetic fields, detected through their synchrotron emission. The
knowledge of the properties of these non-thermal ICM components has increased
significantly, owing to sensitive radio images and to the development of
theoretical models. Diffuse synchrotron radio emission in the central and
peripheral cluster regions has been found in many clusters. Moreover
large-scale magnetic fields appear to be present in all galaxy clusters, as
derived from Rotation Measure (RM) studies. Non-thermal components are linked
to the cluster X-ray properties, and to the cluster evolutionary stage, and are
crucial for a comprehensive physical description of the intracluster medium.
They play an important role in the cluster formation and evolution. We review
here the observational properties of diffuse non-thermal sources detected in
galaxy clusters: halos, relics and mini-halos. We discuss their classification
and properties. We report published results up to date and obtain and discuss
statistical properties. We present the properties of large-scale magnetic
fields in clusters and in even larger structures: filaments connecting galaxy
clusters. We summarize the current models of the origin of these cluster
components, and outline the improvements that are expected in this area from
future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics
Review. 58 pages, 26 figure
Fluconazole for empiric antifungal therapy in cancer patients with fever and neutropenia
BACKGROUND: Several clinical trials have demonstrated the efficacy of fluconazole as empiric antifungal therapy in cancer patients with fever and neutropenia. Our objective was to assess the frequency and resource utilization associated with treatment failure in cancer patients given empiric fluconazole antifungal therapy in routine inpatient care. METHODS: We performed a retrospective cohort study of cancer patients treated with oral or intravenous fluconazole between 7/97 and 6/01 in a tertiary care hospital. The final study cohort included cancer patients with neutropenia (an absolute neutrophil count below 500 cells/mm(3)) and fever (a temperature above 38°C or 100.4°F), who were receiving at least 96 hours of parenteral antibacterial therapy prior to initiating fluconazole. Patients' responses to empiric therapy were assessed by reviewing patient charts. RESULTS: Among 103 cancer admissions with fever and neutropenia, treatment failure after initiating empiric fluconazole antifungal therapy occurred in 41% (95% confidence interval (CI) 31% – 50%) of admissions. Patients with a diagnosis of hematological malignancy had increased risk of treatment failure (OR = 4.6, 95% CI 1.5 – 14.8). When treatment failure occurred the mean adjusted increases in length of stay and total costs were 7.4 days (95% CI 3.3 – 11.5) and $18,925 (95% CI 3,289 – 34,563), respectively. CONCLUSION: Treatment failure occurred in more than one-third of neutropenic cancer patients on fluconazole as empiric antifungal treatment for fever in routine clinical treatment. The increase in costs when treatment failure occurs is substantial
Role of GD3-CLIPR-59 Association in Lymphoblastoid T Cell Apoptosis Triggered by CD95/Fas
We previously found that a directional movement of the raft component GD3 towards mitochondria, by its association with microtubules, was mandatory to late apoptogenic events triggered by CD95/Fas. Since CLIPR-59, CLIP-170-related protein, has recently been identified as a microtubule binding protein associated with lipid rafts, we analyzed the role of GD3-CLIPR-59 association in lymphoblastoid T cell apoptosis triggered by CD95/Fas. To test whether CLIPR-59 could play a role at the raft-microtubule junction, we performed a series of experiments by using immunoelectron microscopy, static or flow cytometry and biochemical analyses. We first assessed the presence of CLIPR-59 molecule in lymphoblastoid T cells (CEM). Then, we demonstrated that GD3-microtubule interaction occurs via CLIPR-59 and takes place at early time points after CD95/Fas ligation, preceding the association GD3-tubulin. GD3-CLIPR-59 association was demonstrated by fluorescence resonance energy transfer (FRET) analysis. The key role of CLIPR-59 in this dynamic process was clarified by the observation that silencing CLIPR-59 by siRNA affected the kinetics of GD3-tubulin association, spreading of GD3 towards mitochondria and apoptosis execution. We find that CLIPR-59 may act as a typical chaperone, allowing a prompt interaction between tubulin and the raft component GD3 during cell apoptosis triggered by CD95/Fas. On the basis of the suggested role of lipid rafts in conveying pro-apoptotic signals these results disclose new perspectives in the understanding of the mechanisms by which raft-mediated pro-apoptotic signals can directionally reach their target, i.e. the mitochondria, and trigger apoptosis execution
Thrombospondin-2 and SPARC/osteonectin are critical regulators of bone remodeling
Thrombospondin-2 (TSP2) and osteonectin/BM-40/SPARC are matricellular proteins that are highly expressed by bone cells. Mice deficient in either of these proteins show phenotypic alterations in the skeleton, and these phenotypes are most pronounced under conditions of altered bone remodeling. For example, TSP2-null mice have higher cortical bone volume and are resistant to bone loss associated with ovariectomy, whereas SPARC-null mice have decreased trabecular bone volume and fail to demonstrate an increase in bone mineral density in response to a bone-anabolic parathyroid hormone treatment regimen. In vitro, marrow stromal cell (MSC) osteoprogenitors from TSP2-null mice have increased proliferation but delayed formation of mineralized matrix. Similarly, in cultures of SPARC-null MSCs, osteoblastic differentiation and mineralized matrix formation are decreased. Overall, both TSP2 and SPARC positively influence osteoblastic differentiation. Intriguingly, both of these matricellular proteins appear to impact MSC fate through mechanisms that could involve the Notch signaling system. This review provides an overview of the role of TSP2 and SPARC in regulating bone structure, function, and remodeling, as determined by both in vitro and in vivo studies
Decomposition cross-correlation for analysis of collagen matrix deformation by single smooth muscle cells
Microvascular remodeling is known to depend on cellular interactions with matrix tissue. However, it is difficult to study the role of specific cells or matrix elements in an in vivo setting. The aim of this study is to develop an automated technique that can be employed to obtain and analyze local collagen matrix remodeling by single smooth muscle cells. We combined a motorized microscopic setup and time-lapse video microscopy with a new cross-correlation based image analysis algorithm to enable automated recording of cell-induced matrix reorganization. This method rendered 60–90 single cell studies per experiment, for which collagen deformation over time could be automatically derived. Thus, the current setup offers a tool to systematically study different components active in matrix remodeling
Characterization of NF-κB reporter U937 cells and their application for the detection of inflammatory immune-complexes
Our study tested the hypothesis that immunoglobulins differ in their ability to activate the nuclear factor-κB pathway mediated cellular responses. These responses are modulated by several properties of the immune complex, including the ratio of antibody isotypes binding to antigen. Immunoassays allow the measurement of antigen specific antibodies belonging to distinct immunoglobulin classes and subclasses but not the net biological effect of the combination of these antibodies. We set out to develop a biosensor that is suitable for the detection and characterization of antigen specific serum antibodies. We genetically modified the monocytoid U937 cell line carrying Fc receptors with a plasmid encoding NF-κB promoter-driven GFP. This clone, U937-NF-κB, was characterized with respect to FcR expression and response to solid-phase immunoglobulins. Human IgG3, IgG4 and IgG1 induced GFP production in a time- and dose-dependent manner, in this order of efficacy, while IgG2 triggered no activation at the concentrations tested. IgA elicited no response alone but showed significant synergism with IgG3 and IgG4. We confirmed the importance of activation via FcγRI by direct stimulation with monoclonal antibody and by competition assays. We used citrullinated peptides and serum from rheumatoid arthritis patients to generate immune complexes and to study the activation of U937-NF-κB, observing again a synergistic effect between IgG and IgA. Our results show that immunoglobulins have distinct pro-inflammatory potential, and that U937-NF-κB is suitable for the estimation of biological effects of immune-complexes, offering insight into monocyte activation and pathogenesis of antibody mediated diseases
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