| 1. |
- Mustjoki, S., et al.
(författare)
-
Clonal expansion of T/NK-cells during tyrosine kinase inhibitor dasatinib therapy
- 2009
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 23:8, s. 1398-1405
-
Tidskriftsartikel (refereegranskat)abstract
- Dasatinib, a broad-spectrum tyrosine kinase inhibitor (TKI), predominantly targets BCR-ABL and SRC oncoproteins and also inhibits off-target kinases, which may result in unexpected drug responses. We identified 22 patients with marked lymphoproliferation in blood while on dasatinib therapy. Clonality and immunophenotype were analyzed and related clinical information was collected. An abrupt lymphocytosis (peak count range 4-20 x 10(9)/l) with large granular lymphocyte (LGL) morphology was observed after a median of 3 months from the start of therapy and it persisted throughout the therapy. Fifteen patients had a cytotoxic T-cell and seven patients had an NK-cell phenotype. All T-cell expansions were clonal. Adverse effects, such as colitis and pleuritis, were common (18 of 22 patients) and were preceded by LGL lymphocytosis. Accumulation of identical cytotoxic T cells was also detected in pleural effusion and colon biopsy samples. Responses to dasatinib were good and included complete, unexpectedly long-lasting remissions in patients with advanced leukemia. In a phase II clinical study on 46 Philadelphia chromosome-positive acute lymphoblastic leukemia, patients with lymphocytosis had superior survival compared with patients without lymphocytosis. By inhibiting immunoregulatory kinases, dasatinib may induce a reversible state of aberrant immune reactivity associated with good clinical responses and a distinct adverse effect profile. Leukemia (2009) 23, 1398-1405; doi:10.1038/leu.2009.46; published online 19 March 2009
|
|
| 2. |
- Ronka, N., et al.
(författare)
-
Near panmixia at the distribution-wide scale but evidence of genetic differentiation in a geographically isolated population of the Terek Sandpiper Xenus cinereus
- 2019
-
Ingår i: Ibis. - : Wiley. - 0019-1019. ; 161:3, s. 632-647
-
Tidskriftsartikel (refereegranskat)abstract
- Populations from different parts of a species range may vary in their genetic structure, variation and dynamics. Geographically isolated populations or those located at the periphery of the range may differ from those located in the core of the range. Such peripheral populations may harbour genetic variation important for the adaptive potential of the species. We studied the distribution-wide population genetic structure of the Terek Sandpiper Xenus cinereus using 13 microsatellite loci and the mitochondrial DNA (mtDNA) control region. In addition, we estimated whether genetic variation changes from the core towards the edge of the breeding range. We used the results to evaluate the management needs of the sampled populations. Distribution-wide genetic structure was negligible; the only population that showed significant genetic differentiation was the geographically isolated Dnieper River basin population in Eastern Europe. The genetic variation of microsatellites decreased towards the edge of the distribution, supporting the abundant-centre hypotheses in which the core area of the distribution preserves the most genetic variation; however, no such trend could be seen with mtDNA. Overall genetic variation was low and there were signs of past population contractions followed by expansion; this pattern is found in most northern waders. The current effective population size (N-e) is large, and therefore global conservation measures are not necessary. However, the marginal Dnieper River population needs to be considered its own management unit. In addition, the Finnish population warrants conservation actions due to its extremely small size and degree of isolation from the main range, which makes it vulnerable to genetic depletion.
|
|
| 3. |
- Rönkä, N., et al.
(författare)
-
Panmixia at a distribution-wide scale but indications of genetic differentiation in isolated populations of the Terek Sandpiper (Xenus cinereus)
- 2016
-
Ingår i: International Wader Study Group Conference 2016, 9-12 September 2016, Trabolgan, Cork, Ireland.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Populations at different parts of the species range may vary in their population dynamics and in their genetic structure and variation. Geographically separated populations or those located at the edge of the range may differ from the populations located at the core, or even be independent of them. The peripheral populations may hold genetic variation that is important for the adaptive potential of the species and therefore be of special conservation value. We studied the distribution-wide population genetic structure of the Terek Sandpiper (Xenus cinereus) using 13 microsatellite loci and two mitochondrial DNA markers: the control region and cytochrome oxidase I (COI). We evaluated the difference in genetic variation between the peripheral and core populations. Specifically, we sought signs of changes in population sizes and evaluated the management need of the populations. Distribution-wide differentiation was negligible, but geographically isolated populations in Finland and Dnieper River basin in Eastern Europe were differentiated from the main range. Edge populations had lower genetic variation than populations at the core when estimated with microsatellites and the COI, supporting the hypotheses where the core area of the distribution preserves the most variation. However, no such trend was observed with the control region data, which follows the model of no change throughout the distribution. The differences between the markers may reflect their different mutation rates, or be linked to the species’ dispersal behaviour. Our results revealed low overall nucleotide diversity and signs of past population contractions followed by expansion. Although the estimated current effective population size is large and therefore global conservation measures are not needed, the Finnish and Dnieper River basin populations nevertheless warrant management actions – not only because they may possess variation not present anywhere else, but also due to their smallness and large distances to the main range.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Paronen, M, et al.
(författare)
-
Preparation of proton-conducting membranes by direct sulfonation. 1. Effect of radicals and radical decay on the sulfonation of poly(vinyl fluoride) films
- 2003
-
Ingår i: Chemistry of Materials. - : American Chemical Society (ACS). - 1520-5002 .- 0897-4756. ; 15:23, s. 4447-4455
-
Tidskriftsartikel (refereegranskat)abstract
- The effect of irradiation treatment on the structure and sulfonation reactivity of polyvinyl fluoride (PVF) films was studied mainly with EPR and IR spectroscopy. The main radical species produced by electron irradiation are aliphatic radicals, whereas proton irradiation creates a significant amount of polyenyl radicals. The half-life time of the aliphatic radicals was about 6 h. FTIR study shows that sulfonation reaction of PVF is a single-stage process and thus the formed sulfonic acid structures do not react further and produce new structures. In addition, it is independent of the irradiation treatment. Despite the careful synthesis and removal of O 2 from the sulfonation solution, the most important side reaction produced by the sulfonation is the formation of C=O functionalities. Irradiation treatment increases the C=O content. Both the sulfonation time and sulfonation reagent concentration demonstrate similar linear correlation with the extent of oxidation. Therefore, the oxidation cannot be decreased by means of optimizing these variables. The only important factor allowing adjustment of the structure of the final membranes is the type of irradiation and radical decay in the case of proton irradiation. Irradiation with either electrons or protons did not increase the ion exchange capacity as measured with a titrimetric method. IR study of the samples showed, however, indication of the formation of derivates of sulfonic acid in the proton-irradiated samples containing radicals.
|
|
