500 research outputs found
Aprotinin reduces cardiac troponin I release and inhibits apoptosis of polymorphonuclear cells during off-pump coronary artery bypass surgery
Objectives: In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. Design: A prospective randomized clinical trial. Setting: University hospital. Participants: Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. Interventions: Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. Measurements and Main Results: Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor a; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (P = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. Conclusions: The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery
Evidence for position effects as a variant ETV6-mediated leukemogenic mechanism in myeloid leukemias with a t(4;12)(q11-q12;p13) or t(5;12)(q31;p13)
The ETV6 gene (first identified as TEL) is a frequent target of chromosomal translocations in both myeloid and lymphoid leukemias. At present, more than 40 distinct translocations have been cytogenetically described, of which 13 have now also been characterized at the molecular level. These studies revealed the generation of in-frame fusion genes between different domains of ETV6 and partner genes encoding either kinases or transcription factors. However, in a number of cases-including a t(6;12)(q23;p13), the recurrent t(5;12)(q31;p13), and some cases of the t(4;12)(q11-q12;p13) described in this work-functionally significant fusions could not be identified, raising the question as to what leukemogenic mechanism is implicated in these cases. To investigate this, we have evaluated the genomic regions at 4q11-q12 and 5q31, telomeric to the breakpoints of the t(4;12)(q11-q12;p13) and t(5;12)(q31;p13). The homeobox gene GSH2 at 4q11-q12 and the IL-3/CSF2 locus at 5q31 were found to be located close to the respective breakpoints. In addition, GSH2 and IL-3 were found to be ectopically expressed in the leukemic cells, suggesting that expression of GSH2 and IL-3 was deregulated by the translocation. Our results indicate that, besides the generation of fusion transcripts, deregulation of the expression of oncogenes could be a variant leukemogenic mechanism for translocations involving the 5' end of ETV6, especially for those translocations lacking functionally significant fusion transcripts
Lenalidomide, melphalan, and prednisone, followed by lenalidomide maintenance, improves health-related quality of life in newly diagnosed multiple myeloma patients aged 65 years or older: results of a randomized phase III trial.
Importance of the structural zinc atom for the stability of yeast alcohol dehydrogenase
Chimeric Antigen Receptor T-Cell Therapy For Multiple Myeloma: A Consensus Statement From The European Myeloma Network
Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strategy has been approved in relapsed/refractory MM, it will become one of the most important indications for this therapy in Europe and world-wide. This manuscript proposes practical considerations for the use of CAR-T cell therapy in MM, and discusses several important issues for its future development
Excitation of the molecular gas in the nuclear region of M82
We present high resolution HIFI spectroscopy of the nucleus of the
archetypical starburst galaxy M82. Six 12CO lines, 2 13CO lines and 4
fine-structure lines are detected. Besides showing the effects of the overall
velocity structure of the nuclear region, the line profiles also indicate the
presence of multiple components with different optical depths, temperatures and
densities in the observing beam. The data have been interpreted using a grid of
PDR models. It is found that the majority of the molecular gas is in low
density (n=10^3.5 cm^-3) clouds, with column densities of N_H=10^21.5 cm^-2 and
a relatively low UV radiation field (GO = 10^2). The remaining gas is
predominantly found in clouds with higher densities (n=10^5 cm^-3) and
radiation fields (GO = 10^2.75), but somewhat lower column densities
(N_H=10^21.2 cm^-2). The highest J CO lines are dominated by a small (1%
relative surface filling) component, with an even higher density (n=10^6 cm^-3)
and UV field (GO = 10^3.25). These results show the strength of multi-component
modeling for the interpretation of the integrated properties of galaxies.Comment: Accepted for publication in A&A Letter
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Ophrys fusca and Ophrys dyris (Orchidaceae) – constancy of tetraploidy amongst populations in Central Portugal
Ophrys is amongst the best known orchid genera and is an established system for the study of pollinatormediated
floral evolution. Two species, Ophrys fusca s.l. and Ophrys dyris (= O. omegaifera subsp. dyris) belonging to Ophrys section Pseudophrys are the focus of this study. In the context of an integrative study of morphological and genetic diversity of O. fusca and O. dyris, genome size (GS) and cytotype diversity were surveyed from Portuguese populations. Flow cytometry methods were used to assess GS, and subsequently determine the ploidy level of 67 specimens, including the species and putative hybrids. Cytotypes were also confirmed based on chromosome counts from the roots of two specimens, one of
each species. Constancy of nuclear DNA content (1C = 11.19 pg) and ploidy level (2n =4x = 72, 74) was
documented among all the individuals analysed. Implications are considered, in terms of interpreting the
origin and predicting the persistence of putative hybrids
Orchid diversity of the cape of Kamenjak (Istria, Croatia)
Twenty two taxa have been recorded in the south of Istrian peninsula (north Adriatic coast, Croatia). The research was performed in the period 2003–2004. A great majority of taxa belong to Euri- Mediterranean (seven taxa, 41.18%) and Steno-Mediterranean (six taxa, 35.29%) floral elements. Eurasiatic (two taxa, 11.76%), Atlantic (one taxa, 5.88%) and endemic (one taxon, 5.88%) plants were also present. Almost a half of recorded orchids are abundant or frequent. The most of taxa are endangered s.l.; nine vulnerable (VU) plants (52.94%), and one species endangered s.s. (EN) (5.88%). There are also near threatened (NT) (two taxa, 11.76%), and data deficient (DD) (one taxon, 5.88%) plants, while others have no category assigned (four taxa, 23.53%)
RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response
Chromosomal region 1p22 is deleted in 6520% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression. Interestingly, RPL5 but not EVI5 mRNA levels were
significantly lower in relapsed patients responding to bortezomib and; both in newly diagnosed and relapsed patients, bortezomib treatment could overcome their bad prognosis by raising their progression-free survival to equal that of patients with high RPL5 expression.
In conclusion, our genetic data restrict the MDR on 1p22 to EVI5 and RPL5 and although the role of these genes in promoting MM progression remains to be determined, we identify RPL5 mRNA expression as a biomarker for initial response to bortezomib in relapsed patients and subsequent survival benefit after long-term treatment in newly diagnosed and relapsed patients
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