158 research outputs found
Merkel cell carcinoma in a 17-year-old boy, report of a highly aggressive fatal case and review of the literature
Merkel cell carcinoma is a rare tumor frequently involving the skin with an aggressive behavior and fatal outcome. It occurs mostly in the caucasian race between 60–80 years of age and it is rare in children. Herein we report our experience with a highly aggressive fatal Merkel cell carcinoma in an immunocompetent 17-year-old boy. Its characteristics and treatment modalities will be also discussed
Penis deformity after intra-urethral liquid paraffin administration in a young male: a case report
This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
Familial aggregation of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with solid tumors and myeloid malignancies.
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Lymphoplasmacytic lymphoma (LPL)/Waldenström macroglobulinemia (WM) is a B-cell disorder resulting from the accumulation, predominantly in the bone marrow, of clonally related lymphoplasmacytic cells. LPL/WM is a very rare disease, with an incidence rate of 3-4 cases per million people per year.Currently, the causes of LPL/WM are poorly understood; however, there are emerging data to support a role for immune-related factors in the pathogenesis of LPL/WM. In addition, data show that genetic factors are of importance in the etiology of LPL/WM. In this paper, we will review the current knowledge about familiality of LPL/WM and provide novel data on solid tumors and myeloid malignancies in first-degree relatives of LPL/WM patients.Swedish Cancer Society
Stockholm County Council
Karolinska Institutet Foundations
National Institutes of Health, National Cancer Institute
Roch
A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia
Genetic predictors of acute toxicities related to radiation therapy following lumpectomy for breast cancer: a case-series study
INTRODUCTION: The cytotoxic effects of radiation therapy are mediated primarily through increased formation of hydroxyl radicals and reactive oxygen species, which can damage cells, proteins and DNA; the glutathione S-transferases (GSTs) function to protect against oxidative stress. We hypothesized that polymorphisms encoding reduced or absent activity in the GSTs might result in greater risk for radiation-associated toxicity. METHODS: Women receiving therapy in radiation units in Germany following lumpectomy for breast cancer (1998–2001) provided a blood sample and completed an epidemiological questionnaire (n = 446). Genotypes were determined using Sequonom MALDI-TOF (GSTA1, GSTP1) and Masscode (GSTM1, GSTT1). Biologically effective radiotherapy dose (BED) was calculated, accounting for differences in fractionation and overall treatment time. Side effects considered were grade 2c and above, as classified using the modified Common Toxicity Criteria. Predictors of toxicity were modelled using Cox regression models in relation to BED, with adjustment for treating clinic, photon field, beam energy and boost method, and potential confounding variables. RESULTS: Low activity GSTP1 genotypes were associated with a greater than twofold increase in risk for acute skin toxicities (adjusted hazard ratio 2.28, 95% confidence interval 1.04–4.99). No associations were noted for the other GST genotypes. CONCLUSION: These data indicate that GSTP1 plays an important role in protecting normal cells from damage associated with radiation therapy. Studies examining the effects of GSTP1 polymorphisms on toxicity, recurrence and survival will further inform individualized therapeutics based on genotypes
Integrating Extrinsic and Intrinsic Cues into a Minimal Model of Lineage Commitment for Hematopoietic Progenitors
Autoregulation of transcription factors and cross-antagonism between lineage-specific transcription factors are a recurrent theme in cell differentiation. An equally prevalent event that is frequently overlooked in lineage commitment models is the upregulation of lineage-specific receptors, often through lineage-specific transcription factors. Here, we use a minimal model that combines cell-extrinsic and cell-intrinsic elements of regulation in order to understand how both instructive and stochastic events can inform cell commitment decisions in hematopoiesis. Our results suggest that cytokine-mediated positive receptor feedback can induce a “switch-like” response to external stimuli during multilineage differentiation by providing robustness to both bipotent and committed states while protecting progenitors from noise-induced differentiation or decommitment. Our model provides support to both the instructive and stochastic theories of commitment: cell fates are ultimately driven by lineage-specific transcription factors, but cytokine signaling can strongly bias lineage commitment by regulating these inherently noisy cell-fate decisions with complex, pertinent behaviors such as ligand-mediated ultrasensitivity and robust multistability. The simulations further suggest that the kinetics of differentiation to a mature cell state can depend on the starting progenitor state as well as on the route of commitment that is chosen. Lastly, our model shows good agreement with lineage-specific receptor expression kinetics from microarray experiments and provides a computational framework that can integrate both classical and alternative commitment paths in hematopoiesis that have been observed experimentally
Channelopathies in Cav1.1, Cav1.3, and Cav1.4 voltage-gated L-type Ca2+ channels
Voltage-gated Ca2+ channels couple membrane depolarization to Ca2+-dependent intracellular signaling events. This is achieved by mediating Ca2+ ion influx or by direct conformational coupling to intracellular Ca2+ release channels. The family of Cav1 channels, also termed L-type Ca2+ channels (LTCCs), is uniquely sensitive to organic Ca2+ channel blockers and expressed in many electrically excitable tissues. In this review, we summarize the role of LTCCs for human diseases caused by genetic Ca2+ channel defects (channelopathies). LTCC dysfunction can result from structural aberrations within their pore-forming α1 subunits causing hypokalemic periodic paralysis and malignant hyperthermia sensitivity (Cav1.1 α1), incomplete congenital stationary night blindness (CSNB2; Cav1.4 α1), and Timothy syndrome (Cav1.2 α1; reviewed separately in this issue). Cav1.3 α1 mutations have not been reported yet in humans, but channel loss of function would likely affect sinoatrial node function and hearing. Studies in mice revealed that LTCCs indirectly also contribute to neurological symptoms in Ca2+ channelopathies affecting non-LTCCs, such as Cav2.1 α1 in tottering mice. Ca2+ channelopathies provide exciting disease-related molecular detail that led to important novel insight not only into disease pathophysiology but also to mechanisms of channel function
Comparison of OH reactivity measurements in the atmospheric simulation chamber SAPHIR
Hydroxyl (OH) radical reactivity (kOH) has been measured for 18 years with different measurement techniques. In order to compare the performances of instruments deployed in the field, two campaigns were conducted performing experiments in the atmospheric simulation chamber SAPHIR at Forschungszentrum Jülich in October 2015 and April 2016. Chemical conditions were chosen either to be representative of the atmosphere or to test potential limitations of instruments. All types of instruments that are currently used for atmospheric measurements were used in one of the two campaigns. The results of these campaigns demonstrate that OH reactivity can be accurately measured for a wide range of atmospherically relevant chemical conditions (e.g. water vapour, nitrogen oxides, various organic compounds) by all instruments. The precision of the measurements (limit of detection < 1 s−1 at a time resolution of 30 s to a few minutes) is higher for instruments directly detecting hydroxyl radicals, whereas the indirect comparative reactivity method (CRM) has a higher limit of detection of 2 s−1 at a time resolution of 10 to 15 min. The performances of the instruments were systematically tested by stepwise increasing, for example, the concentrations of carbon monoxide (CO), water vapour or nitric oxide (NO). In further experiments, mixtures of organic reactants were injected into the chamber to simulate urban and forested environments. Overall, the results show that the instruments are capable of measuring OH reactivity in the presence of CO, alkanes, alkenes and aromatic compounds. The transmission efficiency in Teflon inlet lines could have introduced systematic errors in measurements for low-volatile organic compounds in some instruments. CRM instruments exhibited a larger scatter in the data compared to the other instruments. The largest differences to reference measurements or to calculated reactivity were observed by CRM instruments in the presence of terpenes and oxygenated organic compounds (mixing ratio of OH reactants were up to 10 ppbv). In some of these experiments, only a small fraction of the reactivity is detected. The accuracy of CRM measurements is most likely limited by the corrections that need to be applied to account for known effects of, for example, deviations from pseudo first-order conditions, nitrogen oxides or water vapour on the measurement. Methods used to derive these corrections vary among the different CRM instruments. Measurements taken with a flow-tube instrument combined with the direct detection of OH by chemical ionisation mass spectrometry (CIMS) show limitations in cases of high reactivity and high NO concentrations but were accurate for low reactivity (< 15 s−1) and low NO (< 5 ppbv) conditions
Gas-to-particle partitioning of major biogenic oxidation products: a study on freshly formed and aged biogenic SOA
Secondary organic aerosols (SOAs) play a key role in climate change and air
quality. Determining the fundamental parameters that distribute organic
compounds between the phases is essential, as atmospheric lifetime and
impacts change drastically between the gas and particle phase. In this work,
gas-to-particle partitioning of major biogenic oxidation products was
investigated using three different aerosol chemical characterization
techniques. The aerosol collection module, the collection thermal desorption unit, and the
chemical analysis of aerosols online are different aerosol sampling inlets connected to a proton-transfer reaction time-of-flight
mass spectrometer (ACM-PTR-ToF-MS, TD-PTR-ToF-MS, and CHARON-PTR-ToF-MS, respectively, referred to hereafter as
ACM, TD, and CHARON). These techniques
were deployed at the atmosphere simulation chamber SAPHIR to perform
experiments on the SOA formation and aging from different monoterpenes
(β-pinene, limonene) and real plant emissions (Pinus sylvestris L.). The saturation mass
concentration C* and thus the volatility of the individual ions was
determined based on the simultaneous measurement of their signal in the gas and particle phase.A method to identify and exclude ions affected by thermal dissociation
during desorption and ionic dissociation in the ionization chamber of the
proton-transfer reaction mass spectrometer (PTR-MS) was developed and tested for each technique. Narrow volatility
distributions with organic compounds in the semi-volatile (SVOCs – semi-volatile
organic compounds) to
intermediate-volatility (IVOCs – intermediate-volatility organic compounds) regime were found for all systems studied.
Despite significant differences in the aerosol collection and desorption
methods of the proton-transfer-reaction (PTR)-based techniques, a comparison of the C* values obtained
with different techniques was found to be in good agreement (within 1 order
of magnitude) with deviations explained by the different operating
conditions of the PTR-MS.The C* of the identified organic compounds were mapped onto the
two-dimensional volatility basis set (2D-VBS), and results showed a decrease in C* with increasing oxidation state. For all experiments conducted in
this study, identified partitioning organic compounds accounted for
20–30 % of the total organic mass measured from an aerosol mass spectrometer (AMS). Further
comparison between observations and theoretical calculations was performed
for species found in our experiments that were also identified in previous
publications. Theoretical calculations based on the molecular structure of
the compounds showed, within the uncertainties ranges, good agreement with
the experimental C* for most SVOCs, while IVOCs deviated by up to a factor of
300. These latter differences are discussed in relation to two main
processes affecting these systems: (i) possible interferences by thermal and
ionic fragmentation of higher molecular-weight compounds, produced by
accretion and oligomerization reactions, that fragment in the m∕z range
detected by the PTR-MS and (ii) kinetic influences in the distribution
between the gas and particle phase with gas-phase condensation, diffusion in
the particle phase, and irreversible uptake.</p
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