123 research outputs found
High tumour contamination of leukaphereses in patients with small cell carcinoma of the lung: a comparison of immunocytochemistry and RT-PCR
In small-cell lung carcinoma (SCLC) tumour cell contamination of leukaphereses is unknown. The present study was performed to define appropriate markers for reverse transcriptase polymerase chain reaction (RT-PCR), then to assess the contamination rate of leukaphereses and corresponding bone marrow samples. Immunocytochemistry (ICC) and RT-PCR methods were also compared. Among the 33 patients included, analyses were performed in 16 who had multiple leukaphereses and 17 who had only bone marrow. Leukapheresis products and bone marrow were analysed by ICC using several specific monoclonal antibodies against neural-cell adhesion molecule (N-CAM), epithelial glycoprotein (EGP-40) and cytokeratins (CK). Samples were also analyzed by RT-PCR for expression for N-CAM, synaptophysin, neuron-specific enolase, chromogranin, cytokeratin-18/-19, CEA, EGP-40, apomucin type 1 (MUC-1) and human endothelial cell-specific molecule (ESM-1). Using ICC staining, contaminating tumour cells were detected in 34% of leukaphereses (27% in patients with limited disease and 43% in those with extensive disease). N-CAM was the most reliable marker for detection of contamination. For RT-PCR, CK-19 and CEA were the only appropriate markers. Positive signal rate in leukaphereses increased to 78% (89% for patients with limited disease and 67% for extensive disease). In bone marrow, both techniques were in agreement whereas in leukaphereses, RT-PCR was better than ICC. A high rate of tumour cell contamination was demonstrated not only in bone marrow but also in leukaphereses from SCLC patients. The most appropriate technique was RT-PCR mainly in patients with limited disease. © 2001 Cancer Research Campaign http://www.bjcancer.co
The Milky Way Bulge: Observed properties and a comparison to external galaxies
The Milky Way bulge offers a unique opportunity to investigate in detail the
role that different processes such as dynamical instabilities, hierarchical
merging, and dissipational collapse may have played in the history of the
Galaxy formation and evolution based on its resolved stellar population
properties. Large observation programmes and surveys of the bulge are providing
for the first time a look into the global view of the Milky Way bulge that can
be compared with the bulges of other galaxies, and be used as a template for
detailed comparison with models. The Milky Way has been shown to have a
box/peanut (B/P) bulge and recent evidence seems to suggest the presence of an
additional spheroidal component. In this review we summarise the global
chemical abundances, kinematics and structural properties that allow us to
disentangle these multiple components and provide constraints to understand
their origin. The investigation of both detailed and global properties of the
bulge now provide us with the opportunity to characterise the bulge as observed
in models, and to place the mixed component bulge scenario in the general
context of external galaxies. When writing this review, we considered the
perspectives of researchers working with the Milky Way and researchers working
with external galaxies. It is an attempt to approach both communities for a
fruitful exchange of ideas.Comment: Review article to appear in "Galactic Bulges", Editors: Laurikainen
E., Peletier R., Gadotti D., Springer Publishing. 36 pages, 10 figure
Impact of non-axillary sentinel node biopsy on staging and treatment of breast cancer patients
The purpose of this study was to evaluate the occurrence of lymphatic drainage to non-axillary sentinel nodes and to determine the implications of this phenomenon. A total of 549 breast cancer patients underwent lymphoscintigraphy after intratumoural injection of 99mTc-nanocolloid. The sentinel node was intraoperatively identified with the aid of intratumoural administered patent blue dye and a gamma-ray detection probe. Histopathological examination of sentinel nodes included step-sectioning at six levels and immunohistochemical staining. A sentinel node outside level I or II of the axilla was found in 149 patients (27%): internal mammary sentinel nodes in 86 patients, other non-axillary sentinel nodes in 44 and both internal mammary and other non-axillary sentinel nodes in nineteen patients. The intra-operative identification rate was 80%. Internal mammary metastases were found in seventeen patients and metastases in other non-axillary sentinel nodes in ten patients. Staging improved in 13% of patients with non-axillary sentinel lymph nodes and their treatment strategy was changed in 17%. A small proportion of clinically node negative breast cancer patients can be staged more precisely by biopsy of sentinel nodes outside level I and II of the axilla, resulting in additional decision criteria for postoperative regional or systemic therapy
SUMO-Interacting Motifs of Human TRIM5α are Important for Antiviral Activity
Human TRIM5α potently restricts particular strains of murine leukemia viruses
(the so-called N-tropic strains) but not others (the B- or NB-tropic strains)
during early stages of infection. We show that overexpression of SUMO-1 in human
293T cells, but not in mouse MDTF cells, profoundly blocks N-MLV infection. This
block is dependent on the tropism of the incoming virus, as neither B-, NB-, nor
the mutant R110E of N-MLV CA (a B-tropic switch) are affected by SUMO-1
overexpression. The block occurred prior to reverse transcription and could be
abrogated by large amounts of restricted virus. Knockdown of TRIM5α in 293T
SUMO-1-overexpressing cells resulted in ablation of the SUMO-1 antiviral
effects, and this loss of restriction could be restored by expression of a human
TRIM5α shRNA-resistant plasmid. Amino acid sequence analysis of human
TRIM5α revealed a consensus SUMO conjugation site at the N-terminus and
three putative SUMO interacting motifs (SIMs) in the B30.2 domain. Mutations of
the TRIM5α consensus SUMO conjugation site did not affect the antiviral
activity of TRIM5α in any of the cell types tested. Mutation of the SIM
consensus sequences, however, abolished TRIM5α antiviral activity against
N-MLV. Mutation of lysines at a potential site of SUMOylation in the CA region
of the Gag gene reduced the SUMO-1 block and the TRIM5α restriction of
N-MLV. Our data suggest a novel aspect of TRIM5α-mediated restriction, in
which the presence of intact SIMs in TRIM5α, and also the SUMO conjugation
of CA, are required for restriction. We propose that at least a portion of the
antiviral activity of TRIM5α is mediated through the binding of its SIMs to
SUMO-conjugated CA
Peroxisomal alterations in Alzheimer’s disease
In Alzheimer’s disease (AD), lipid alterations are present early during disease progression. As some of these alterations point towards a peroxisomal dysfunction, we investigated peroxisomes in human postmortem brains obtained from the cohort-based, longitudinal Vienna-Transdanube Aging (VITA) study. Based on the neuropathological Braak staging for AD on one hemisphere, the patients were grouped into three cohorts of increasing severity (stages I–II, III–IV, and V–VI, respectively). Lipid analyses of cortical regions from the other hemisphere revealed accumulation of C22:0 and very long-chain fatty acids (VLCFA, C24:0 and C26:0), all substrates for peroxisomal β-oxidation, in cases with stages V–VI pathology compared with those modestly affected (stages I–II). Conversely, the level of plasmalogens, which need intact peroxisomes for their biosynthesis, was decreased in severely affected tissues, in agreement with a peroxisomal dysfunction. In addition, the peroxisomal volume density was increased in the soma of neurons in gyrus frontalis at advanced AD stages. Confocal laser microscopy demonstrated a loss of peroxisomes in neuronal processes with abnormally phosphorylated tau protein, implicating impaired trafficking as the cause of altered peroxisomal distribution. Besides the original Braak staging, the study design allowed a direct correlation between the biochemical findings and the amount of neurofibrillary tangles (NFT) and neuritic plaques, quantified in adjacent tissue sections. Interestingly, the decrease in plasmalogens and the increase in VLCFA and peroxisomal volume density in neuronal somata all showed a stronger association with NFT than with neuritic plaques. These results indicate substantial peroxisome-related alterations in AD, which may contribute to the progression of AD pathology
Advances in the therapy of Alzheimer's disease: Targeting amyloid beta and tau and perspectives for the future
Worldwide multidisciplinary translational research has led to a growing knowledge of the genetics and molecular pathogenesis of Alzheimer's disease (AD) indicating that pathophysiological brain alterations occur decades before clinical signs and symptoms of cognitive decline can be diagnosed. Consequently, therapeutic concepts and targets have been increasingly focused on early-stage illness before the onset of dementia; and distinct classes of compounds are now being tested in clinical trials. At present, there is a growing consensus that therapeutic progress in AD delaying disease progression would significantly decrease the expanding global burden. The evolving hypothesis- and evidence-based generation of new diagnostic research criteria for early-stage AD has positively impacted the development of clinical trial designs and the characterization of earlier and more specific target populations for trials in prodromal as well as in pre- and asymptomatic at-risk stages of AD
State of the Field: Extreme Precision Radial Velocities
The Second Workshop on Extreme Precision Radial Velocities defined circa 2015
the state of the art Doppler precision and identified the critical path
challenges for reaching 10 cm/s measurement precision. The presentations and
discussion of key issues for instrumentation and data analysis and the workshop
recommendations for achieving this precision are summarized here.
Beginning with the HARPS spectrograph, technological advances for precision
radial velocity measurements have focused on building extremely stable
instruments. To reach still higher precision, future spectrometers will need to
produce even higher fidelity spectra. This should be possible with improved
environmental control, greater stability in the illumination of the
spectrometer optics, better detectors, more precise wavelength calibration, and
broader bandwidth spectra. Key data analysis challenges for the precision
radial velocity community include distinguishing center of mass Keplerian
motion from photospheric velocities, and the proper treatment of telluric
contamination. Success here is coupled to the instrument design, but also
requires the implementation of robust statistical and modeling techniques.
Center of mass velocities produce Doppler shifts that affect every line
identically, while photospheric velocities produce line profile asymmetries
with wavelength and temporal dependencies that are different from Keplerian
signals.
Exoplanets are an important subfield of astronomy and there has been an
impressive rate of discovery over the past two decades. Higher precision radial
velocity measurements are required to serve as a discovery technique for
potentially habitable worlds and to characterize detections from transit
missions. The future of exoplanet science has very different trajectories
depending on the precision that can ultimately be achieved with Doppler
measurements.Comment: 45 pages, 23 Figures, workshop summary proceeding
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