165 research outputs found
Serological identification of HSP105 as a novel non-Hodgkin lymphoma therapeutic target.
We reported that the clinical efficacy of dendritic cell-based vaccination is strongly associated with immunologic responses in relapsed B-cell non-Hodgkin lymphoma (B-NHL) patients. We have now investigated whether postvaccination antibodies from responders recognize novel shared NHL-restricted antigens. Immunohistochemistry and flow cytometry showed that they cross-react with allogeneic B-NHLs at significantly higher levels than their matched prevaccination samples or nonresponders' antibodies. Western blot analysis of DOHH-2 lymphoma proteome revealed a sharp band migrating at approximately 100 to 110 kDa only with postvaccine repertoires from responders. Mass spectrometry identified heat shock protein-105 (HSP105) in that molecular weight interval. Flow cytometry and immunohistochemistry disclosed HSP105 on the cell membrane and in the cytoplasm of B-NHL cell lines and 97 diagnostic specimens. A direct correlation between HSP105 expression and lymphoma aggressiveness was also apparent. Treatment of aggressive human B-NHL cell lines with an anti-HSP105 antibody had no direct effects on cell cycle or apoptosis but significantly reduced the tumor burden in xenotransplanted immunodeficient mice. In vivo antilymphoma activity of HSP105 engagement was associated with a significant local increase of Granzyme B(+) killer cells that very likely contributed to the tumor-restricted necrosis. Our study adds HSP105 to the list of nononcogenes that can be exploited as antilymphoma targets
Post-graduate medical education in public health: The case of Italy and a call for action
Public health technical expertise is of crucial importance to inform decision makers\u2019
action in the field of health and its broader determinants. Improving education and
training of public health professionals for both practice and research is the starting
point to strengthen the role of public health so that current health challenges can
be efficiently tackled. At the Association of Schools of Public Health in the European
Region (ASPHER) Deans\u2019 & Directors\u2019 2017 Annual Retreat, we presented the structure
and management of public health training system in Italy, and we reported recent data
on Italian public health specialists\u2019 educational experience, employment opportunities
and job satisfaction. Public health training in Italy is implemented in the context
of the post-graduate medical education residency programme in Hygiene and
Preventive Medicine, delivered by 34 University-based Schools of Public Health.
We report relatively high employment rates across the county and wide
spectrum of career opportunities for young public health specialists. However,
job security is low and training expectations only partially met. We call upon
other Schools of Public Health to scale up the survey within the broad ASPHER
community in a shared and coordinated action of systematically collecting useful
data that can inform the development of public health education and training
models, their implementation and fruitful interaction with population health,
health systems and services
CD95 death-inducing signaling complex formation and internalization occur in lipid rafts of type I and type II cells
We investigated the membrane localization of CD95 in type I and type II cells, which differ in their ability to recruit and activate caspase-8. We found that CD95 was preferentially located in lipid rafts of type I cells, while it was present both in raft and non-raft plasma membrane sub-domains of type II cells. After stimulation, CD95 located in phospholipid-rich plasma membrane was recruited to lipid rafts in both types of cells. Similarly, CD95 cross-linking resulted in caspase-independent translocation of FADD/MORT1 and caspase-8 to the lipid rafts, which was prevented by a death domain-defective receptor. CD95 internalization was then rapid in type I and delayed in type II cells and showed a substantial correlation with the kinetics of Fas-associated death domain (FADD) and caspase-8 recruitment to lipid rafts. Finally, electron microscopy analysis showed that after CD95 stimulation lipid rafts aggregated in large clusters that were internalized in endosomal vesicles, where caspase-8 underwent massive processing. Taken together, our data demonstrate that CD95 death-inducing signaling complex formation and internalization in type I and type II cells occur in lipid rafts, which are a major site of caspase-8 activation. © 2004 WILEY-VCH Verlag GmbH & Co. KGaA
The first period of the 2002 Etna eruption (27 October-5 November): preliminary results
We report on the first period of the 2002 Etna eruption started on 27th October and ended on 5th November, occurring 15 months after the end of the 2001 eruption. Volcanological and geochemical data are presented in order to characterize the complex intrusion mechanism that contemporaneously involved the NE and S flanks of the volcano. Preliminary data outline that two distinct magma intrusions fed the eruptive fissures. Strong fire fountain activity mainly from the S fissure, produced copious ash fall in eastern Sicily, causing prolonged closure of Catania and Reggio Calabria airports. Lava emitted from the NE fissure formed a 6.2 km long lava flow field that destroyed the tourist facilities of Piano Provenzana area and part of Linguaglossa pine forest.Published1-10reserve
Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen
High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose (18FFDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had 18FFDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments
Search for Event Rate Modulation in XENON100 Electronic Recoil Data
We have searched for periodic variations of the electronic recoil event rate
in the (2-6) keV energy range recorded between February 2011 and March 2012
with the XENON100 detector, adding up to 224.6 live days in total. Following a
detailed study to establish the stability of the detector and its background
contributions during this run, we performed an un-binned profile likelihood
analysis to identify any periodicity up to 500 days. We find a global
significance of less than 1 sigma for all periods suggesting no statistically
significant modulation in the data. While the local significance for an annual
modulation is 2.8 sigma, the analysis of a multiple-scatter control sample and
the phase of the modulation disfavor a dark matter interpretation. The
DAMA/LIBRA annual modulation interpreted as a dark matter signature with
axial-vector coupling of WIMPs to electrons is excluded at 4.8 sigma.Comment: 6 pages, 4 figure
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
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