1,721,015 research outputs found
Definition of a HLA class II restricted HCMV peptide
No full textDie HCMV-Infektion stellt für Patienten nach allogener Stammzelltransplantation nach wie vor eine lebensbedrohliche Erkrankung dar. Da die medikamentöse Behandlung der HCMV-Infektion mit schweren Nebenwirkungen verbunden ist und zudem immer häufiger von Virustatika-resistenten HCMV-Stämmen berichtet wird, stellt die adoptive Immuntherapie eine wichtige alternative Therapieoption dar.
Es gibt viele Hinweise darauf, dass für eine dauerhafte zelluläre Immunität gegenüber HCMV bzw. für die Aufrechterhaltung einer ausreichend hohen CD8+ T-Zellanzahl und -funktion CD4+ T-Zellen eine entscheidende Bedeutung zukommt.
In der vorliegenden Arbeit wurde nun versucht, aufgrund einer computerbasierten Epitopvorhersage aus einer Vielzahl von Peptiden, HCMV-spezifische HLA-Klasse-II-restringierte Peptide zu definieren, welche in der Lage sein sollten, CD4+ T-Zellen spezifsch zu stimulieren.
Die vergleichend eingesetzten Methoden umfassten einen unspezischen Proliferationsassay, die konventionelle PCR sowie die RT-PCR. In der PCR wurde jeweils IFN-gamma als Ausdruck einer T-Zell-Stimulation quantifiziert.
Bei gesunden Blutspendern konnte mit diesem Ansatz ein allerdings bereits bekanntes HLA-II-DR11-restringiertes HCMV-Peptid definiert werden, dessen Potenz, CD4+ T-Zellen zu stimulieren, in der durchgeführten konventionellen PCR, dem Prolifera-tionstest sowie dem Light Cycler®-Protokoll dokumentiert werden konnte.
Weitere Analysen sollten sich zukünftig auf Patienten mit kurz zurückliegender HCMV-Infektion konzentrieren, da diese sicherlich höhere Frequenzen HCMV-spezifischer T-Zellen aufweisen.Human Cytomegalovirus (HCMV) is a common herpes virus that can cause significant morbidity and mortality in immunocompromised individuals, particularly those undergoing allogeneic stem cell transplantation for hematological malignancies. Knowledge of CD8 and CD4 T cell epitopes from HCMV and their immunodominant features is crucial for the generation of epitope-specific T cells for adoptive immunotherapy and for the development of a peptide-based HCMV vaccine.
It is clear that HCMV-specific CD4 cells provide helper functions facilitating long-term persistence of CD8 T cells and persistence of robust virus-specific CD4 T cells are important components of protective immunity in chronic HCMV infection.
This work's aim was to define HCMV-specific HLA class II restricted peptides being able to stimulate CD4 T cells specifically.
The used methods included an unspecific proliferation assay, conventional PCR and RT-PCR. IFN-gamma was quantified showing the T-cell stimulation.
With healthy blood donors in this way a - however already known - HLA-II-DR11 restricted peptide able to stimulate CD4 T cells could be defined.
Further analysis should concentrate on patients with recent HCMV-infection as these patients surely have higher frequencies of HCMV specific T cells
Analysis of folate and methotrexate-metabolizing genes in patients with primary CNS lymphoma
No full textDas primäre ZNS-Lymphom ist eine seltene Form eines hoch-malignen, extranodalen Non-Hodgkin-Lymphoms mit steigender Inzidenz in den letzten Jahrzehnten. Hochdosiertes Methotrexat zählt bei intravenöser Verabreichung zu den wirksamsten Therapieoptionen in der Primärtherapie, allerdings mit zum Teil erheblichen Nebenwirkungen.
Diese Nebenwirkungen scheinen zum Teil mit Polymorphismen in Genen des Folsäurestoffwechsels assoziiert zu sein. Fünf der Polymorphismen wurden in dieser Arbeit untersucht: Zwei in der Methylentetrahydrofolatreduktase (SNP MTHFR C677T, SNP MTHFR A1298C), einer im reduzierten Folat-Carrierprotein (SNP RFC G80A) und zwei in der Thymidylat-Synthase (TS 5’UTR 28bp tandem/triplet repeat, TS 3’UTR 1498del6). Die Punktmutationen in der MTHFR und im RFC wurden mittels Schmelzkurvenanalyse im LightCycler®, der 28 bp tandem/triplet repeat der TS mittels konventioneller PCR und Agarose Gel-Elektrophorese und die 6 bp Deletion der TS mit konventioneller PCR, Restriktionsenzymverdau durch Dra I und Agarose Gel-Elektrophorese nachgewiesen.
Das Patientenkollektiv rekrutierte sich aus 156 Teilnehmern der G-PCNSL-SG-1 Studie, die sich mit dem Stellenwert der Ganzhirnbestrahlung in der Primärtherapie primärer ZNS-Lymphome mit Hochdosis-Methotrexat befasst. Von 143 Patienten wurden die Nebenwirkungen nach der WHO Skala (Grad 0 bis IV) mit jedem verabreichten Zyklus MTX erfasst.
Der TT-Genotyp des SNP MTHFR C677T korrelierte signifikant mit dem Parameter „schwerste dokumentierte Nebenwirkung“ (p=0,007) und dem Parameter „nicht-hämatologische Nebenwirkung“ (p=0,007). In beiden Fällen zeigten Patienten mit dem TT-Genotyp die schwereren Nebenwirkungen.
Patienten mit dem GG-Genotyp des SNP RFC G80A zeigten eine signifikant höhere Wahrscheinlichkeit (p=0,04) eine Grad III/IV Granulozytopenie zu erleiden als Patient mit mindestens einem A-Allel. Der SNP MTHFR A1298C und die Polymorphismen der Thymidylat-Synthase zeigten keine signifikante Korrelation mit den erfassten Nebenwirkungen der Therapie.
Die untersuchten Polymorphismen hatten keinen Einfluß auf das overall und progression free survival.
Anhand von 154 Patienten wurden für die oben genannten Polymorphismen die Allelfrequenzen innerhalb der Studienpopulation errechnet. Beim Vergleich dieser Allelfrequenzen mit denen gesunder Vergleichspopulationen zeigte sich, dass der TT-Genotyp des SNP MTHFR C677T bei Patienten kaukasischer Herkunft mit dem Risiko für ein PCNSL korreliert (p=0,04). Diese Korrelation konnte erstmals für das PCNSL aufgezeigt werden. Anderen Arbeitsgruppen war dies schon bei Lymphomen außerhalb des ZNS gelungen. Weiterhin zeigte sich, dass die homozygote Variante des triplet repeat (3R3R) der TS ebenfalls mit dem Risiko für ein PCNSL korreliert (p=0,02).
Die Ergebnisse belegen, dass Polymorphismen im Folsäure- und Methotrexat-Stoffwechsel an der Krankheitsentstehung und am Auftreten von Methotrexat-induzierten Nebenwirkungen beteiligt sein können.Primary CNS lymphoma is a rare entity of extranodal Non-Hodgkin-lymphoma. The incidence is emerging in the last decades. The antifolate methotrexate (MTX) was shown to be the single most-effective agent in first-line treatment of patients with primary central nervous system lymphoma (PCNSL) when given intravenously in high doses, however accompanied by severe side effects.
These side effects are supposed to be associated with polymorphisms in genes of the folate cycle: Two in the gene of the methylenetetrahydrofolate reductase (SNP MTHFR C677T, SNP MTHFR A1298C), one in the reduced folate carrier (SNP RFC G80A) and two in the thymidylate synthase (a 6bp deletion in the 3’UTR and a 28bp tandem/triplet repeat in the 5’UTR) were studied.
The SNPs in the MTHFR and RFC were analyzed by melting curve technique via LightCycler®, the tandem/triplet repeat polymorphism was conventionally analyzed by pcr and agarose gel-electrophoresis, the 6 bp deletion in TS was analyzed by pcr, adjacent enzyme digest by Dra I and following agarose gel-electrophoresis.
156 participants were recruited from the G-PCNSL-SG-1 study, which deals with the value of whole brain irradiation of PCNSL under high-dose methotrexate therapy. The therapy-related side effects of 143 participants were gathered according to the WHO (grade 0 to 4) after each administered cycle of MTX.
The TT genotype of MTHFR C677T showed a significant correlation with the “maximal documented adverse reaction” (p=0,007) and the “non-hematological adverse reaction” (p=0,007). The GG genotype of SNP RFC G80A was significantly associated with a grade III/IV neutropenia in comparison to patients with at least one A-allele (p=0,04).The SNP MTHFR A1298C and the two polymorphisms in the thymidylate synthase showed no association with the collected data.
Furthermore the overall survival and the progression free survival were related to the analyzed polymorphisms but showed no significant result.
With the data of 154 patients allele frequencies of the aforementioned polymorphisms were calculated. The TT genotype of SNP MTHFR C677T was significantly correlated with the risk of PCNSL in a Caucasian population (p=0,04). In PCNSL this is the first evidence of this association, in other lymphoma this fact was mentioned before. Also the homozygous variant of the triplet repeat of TS (3R3R) was correlated with the risk for suffering from PCNSL (p=0,02).
These results show the central role of the aforementioned polymorphisms in the folate and methotrexate metabolism and reveal that they are involved in pathogenesis of PCNSL and in occurrence of MTX-induced side effects
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Haematology and Oncology
No full textPatients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Bacteria and fungi predominate the first phase until engraftment. During the second phase, from engraftment to about day 100, major infectious problems are caused by fungi and cytomegalovirus. Both pathogens remain important under continued immunosuppression, however, in the late post-transplantation period infections with encapsulated bacteria may become a problem. In this review the Infectious Diseases Working Party of the DGHO gives recommendations for prophylaxis of infections under allogeneic stem cell transplantation with drugs and other measures. The aim of the group was to do this on an evidence-based-medicine rating, if possible
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