Detecting T-cell Reactivity to Whole Cell Vaccines

BCR-ABL$^+$ K562 cells hold clinical promise as a component of cancer vaccines, either as bystander cells genetically modified to express immunostimulatory molecules, or as a source of leukemia antigens. To develop a method for detecting T-cell reactivity against K562 cell-derived antigens in patients, we exploited the dendritic cell (DC)-mediated cross-presentation of proteins generated from apoptotic cells. We used UVB irradiation to consistently induce apoptosis of K562 cells, which were then fed to autologous DCs. These DCs were used to both stimulate and detect antigen-specific CD8+ T-cell reactivity. As proof-of-concept, we used cross-presented apoptotic influenza matrix protein-expressing K562 cells to elicit reactivity from matrix protein-reactive T cells. Likewise, we used this assay to detect increased anti-CML antigen T-cell reactivity in CML patients that attained long-lasting clinical remissions following immunotherapy (donor lymphocyte infusion), as well as in 2 of 3 CML patients vaccinated with lethally irradiated K562 cells that were modified to secrete high levels of granulocyte macrophage colony-stimulating factor (GM-CSF). This methodology can be readily adapted to examine the effects of other whole tumor cell-based vaccines, a scenario in which the precise tumor antigens that stimulate immune responses are unknown

Ancient DNA reveals twenty million years of aquatic life in beavers

Xenikoudakis et al. report a partial mitochondrial genome of the extinct giant beaver Castoroides and estimate the origin of aquatic behavior in beavers to approximately 20 million years. This time estimate coincides with the extinction of terrestrial beavers and raises the question whether the two events had a common cause

Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials.

The optimal treatment of acute myeloid leukemia (AML) in first complete remission (CR1) is uncertain. Current consensus, based on cytogenetic risk, recommends myeloablative allogeneic stem cell transplantation (SCT) for poor-risk but not for good-risk AML. Allogeneic SCT, autologous transplantation, and consolidation chemotherapy are considered of equivalent benefit for intermediate-risk AML

Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia

We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20-27%) and a median OS of 3.3 months (95% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36-50%) and a median OS of 6.1 months (95% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67-4.31) and improved OS (HR=0.536, 95% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data

Stable Isotope Analysis of the Inca Mummy from Nevado de Chuscha (Salta, Argentina)

This paper presents the carbon (13C/12C), nitrogen (15N/14N), oxygen (18O/16O), hydrogen (2H/1H) and sulfur (34S/32S) stable isotope values measured in the hair of a female individual from north-western Argentina. The analysis of segments of this tissue allows for the recording of the diet and migratory changes with a short time resolution. The sample is from a mummified young female individual discovered in Chuscha mount, Salta province. It was found at more than 5000 masl, in a mountain sanctuary of the Inca expansion (capacochas). The paper discusses the paleodiet and mobility patterns of this individual in the period before her death, focusing on the isotopic variations in a limited time scale. The results indicate that the individual moved from a different region to the place where she was sacrificed. Furthermore, in the last year the individual was alive, a shift in the isotopic composition of the food consumed is detected: a variation in the importance of C4 over C3 resources is evident. The results are compared with the isotopic estimations for other children and young people recovered in archaeological contexts associated with capacochas to infer variability in the geographical trajectories covered during their last months of life.Fil: Killian Galván, Violeta Anahí. Universidad de Buenos Aires. Facultad de Filosofía y Letras. Instituto Interdisciplinario Tilcara; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tessone, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Valenzuela, Luciano Oscar. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Sociales. Departamento de Arqueología. Laboratorio de Ecología Evolutiva Humana (Sede Quequén); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sharp, Z. D.. Universidad de Nuevo México.; Estados UnidosFil: Panarello, Hector Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; Argentin

Quantitative assay for the detection of the V617F variant in the Janus kinase 2 (JAK2) gene using the Luminex xMAP technology

<p>Abstract</p> <p>Background</p> <p>The availability of clinically valid biomarkers contribute to improve the diagnosis and clinical management of diseases. A valine-to-phenylalanine substitution at position 617 (V617F) in the Janus kinase 2 (JAK2) gene has been recently associated with key signaling abnormalities in the transduction of haemopoietic growth-factor receptors and is now considered as a useful clinical marker of myeloproliferative neoplasms. Several methods have recently been reported to detect the JAK2 V617F point mutation and show variable sensitivity.</p> <p>Methods</p> <p>Using the Luminex xMAP technology, we developed a quantitative assay to detect the JAK2V617F variant. The method was based on polymerase chain reaction (PCR) followed by hybridization to specific probes coupled with internally dyed microspheres. The assay comprises 3 steps: genomic DNA extraction, end point PCR reaction, direct hybridization of PCR fragments and quantification. It has been tested with different sources of nucleic acid.</p> <p>Results</p> <p>Applied to whole blood samples, this quantitative assay showed a limit of detection of 2%. A highly sensitive allele-specific primer extension reaction performed in parallel allowed to validate the results and to identify the specimens with values below 2%.</p> <p>Conclusion</p> <p>Direct hybridization assay using the Luminex xMAP technology allows sensitive quantification of JAK2V617F from blood spots. It is simple and can be easily performed in a clinical setting.</p

Weather and our food supply

The steep rate of increase in yield of grain crops in the United States since the mid-1950\u27s has resulted in the use of the term explosion in technology. Surplus grains piled up to such proportions after the 1960 · harvest that acreage control appeared. to be in order. But despite substantial reductions in acreages after 1960 the increased output per acre has just about compensated for acreage reductions. During this period of rapid increase in output per acre there has been a growing tendency to believe that technology has reduced the influence of weather on grain production so that we no longer need to fear shortages due to unfavorable weather. There is also a popular belief that acreage control$ fail to achieve the objective of production control, and that public funds are being wasted in storing surplus grains which we don\u27t need. There is increasing evidence, however, that a period of favorable weather interacted with technology to produce our recent high yields, and that perhaps half of the increase in yield per acre since 1950 has been due to a change to more favorable weather for grain crops. These findings have important implications in continued support for research in production technology and in the way in which we look at our surplus stocks of feed and food grains. If a period of favorable weather has been responsible for half of the increase in yields since 19501 then what can we expect if the weather trend reverses itself for a few years? Do we have periodicity in weather, and have we just passed through a run of favorable years that might be followed by a run of unfavorable years? Should we treat our surplus grains as reserves? How does our rate of growth in grain output compare with the needs of a growing world population? And of course I in the background of these questions is one big question -- how much of our recent high yields is really due to weather? To answer these important questions the Center for Agriculture and Economic Development invited outstanding authorities to present their ideas under three main headings: (1) Techniques for Evaluation of Weather Variables in Agricultural Production I (2) Periodicity in Weather Patterns: Implications in Agriculture I and (3) Weather Considerations in Agricultural Policy. The papers have been assembled in the order of their presentation under the general outline above.https://lib.dr.iastate.edu/card_reports/1021/thumbnail.jp

Relevance of JAK2V617F positivity to hematological diseases - survey of samples from a clinical genetics laboratory

<p>Abstract</p> <p>Background</p> <p>JAK2V617F is found in the majority of patients with Ph- myeloproliferative neoplasms (MPNs) and has become a valuable marker for diagnosis of MPNs. However, it has also been found in many other hematological diseases, and some studies even detected the presence of JAK2V617F in normal blood samples. This casts doubt on the primary role of JAK2V617F in the pathogenesis of MPNs and its diagnostic value.</p> <p>Methods</p> <p>In the present study, we analyzed JAK2V617F positivity with 232 normal blood samples and 2663 patient blood, bone marrow, and amniotic fluid specimens obtained from a clinical genetics laboratory by using a simple DNA extraction method and a sensitive nested allele-specific PCR strategy.</p> <p>Results</p> <p>We found JAK2V617F present in the majority (78%) of MPN patients and in a small fraction (1.8-8.7%) of patients with other specific hematological diseases but not at all in normal healthy donors or patients with non-hematological diseases. We also revealed associations of JAK2V617F with novel as well as known chromosomal abnormalities.</p> <p>Conclusions</p> <p>Our study suggests that JAK2V617F positivity is associated with specific hematological malignancies and is an excellent diagnostic marker for MPNs. The data also indicate that the nested allele-specific PCR method provides clinically relevant information and should be conducted for all cases suspected of having MPNs as well as for other related diseases.</p