Summary. Although it has been known for more than 40 years that allogeneic immune responses cure leukaemias after bone marrow transplantation, autologous leukaemiaspecific immunity remains controversial and its impact upon survival has not been established. Here we have tested 25 patients with de novo acute leukaemias, while in remission at completion of their anti-leukaemia therapy, for evidence of autologous cytolytic immunity to their leukaemic cells taken and cryopreserved at disease presentation. We have measured this degree of cell-mediated cytotoxicity in vitro and termed it Ôleukaemia cytolytic activityÕ (LCA). Patients whose disease ultimately relapsed had significantly lower LCA than those who remained in remission beyond 2 years (P < 0AE001); the absence of LCA when in remission predicted subsequent relapse within 2 years with a sensitivity of 100% and specificity of 77%. LCA was mediated in vitro by CD56 + /CD8a + /CD3 -natural killer cells. We propose that it is this immune response, rather than the chemotherapy per se, which is responsible for continued remission and that measurement of LCA in patients at completion of therapy may be used as an indicator of risk of subsequent relapse. Patients lacking this response will require further treatment, either with an allogeneic donor transplant or an alternative immunotherapeutic strategy.
With the objective of identifying candidate tumor suppressor genes, we used fluorescence in situ hybridization to map leukemia-related deletions of the long arm of chromosome 6 (6q). Twenty of 24 deletions overlapped to define a 4.8-Mb region of minimal deletion between markers D6S1510 and D6S1692 within chromosome 6 band q16. Using reverse transcription-PCR, we found evidence of expression in hematopoietic cells for 3 of 15 genes in the region (GRIK2, C6orf111, and CCNC). Comparison between our own and published deletion data singled out GRIK2 as the gene most frequently affected by deletions of 6q in acute lymphocytic leukemia (ALL). Sequence analysis of GRIK2 in 14 ALL cases carrying heterozygous 6q deletions revealed a constitutional and paternally inherited C to G substitution in exon 6 encoding for an amino acid change in one patient. The substitution was absent among 232 normal alleles tested, leaving open the possibility that heterozygous carriers of such mutations may be susceptible to ALL. Although low in all normal hematopoietic tissues, quantitative reverse transcription-PCR showed higher baseline GRIK2 expression in thymus and T cells than other lineages. Among T-cell ALL patients, 6q deletion was associated with a statistically significant reduction in GRIK2 expression (P ؍ 0.0001). By contrast, elevated GRIK2 expression was measured in the myelomonocytic line THP-1 and in one patient with common ALL. Finally, we detected significant levels of GRIK2 expression in prostate, kidney, trachea, and lung, raising the possibility that this gene may be protective against multiple tumor types.
We are writing in regard to your published article "Isolation of endothelial cells and their progenitor cells from human peripheral blood" (J Vasc Surg 2000;31:181-9).We read with interest Boyer et al's article in Journal of Vascular Surgery. 1 We have been evaluating endothelial cell extraction from many sources and seeding of vascular prosthesis for many years; therefore, we investigated the possibility of cell extraction from this source. The evidence so far suggests that endothelial seeding of prosthetic graft improves graft patency only when the source of the endothelial cells is vein and when the cells are cultured. 2,3 The recent report by Boyer et al has described peripheral blood as another source of endothelial cells for seeding vascular prosthesis. These cells were extracted using CD34+ monoclonal antibody and then require prolonged culture for 18 days before a typical cobblestone appearance was observed. However, in their article, Boyer et al have not mentioned the total number of CD34+ cells extracted from the 50 mL of blood and the purity of their CD34+ cell extraction. To gather the feasibility of this source for seeding of prosthetic graft, we undertook extraction of CD34+ cells from peripheral blood using a commercial anti-CD34+ monoclonal antibody (HPCA-2, BD, Oxford, United Kingdom).A 29-year-old healthy volunteer had 50 mL of blood collected into a tube containing 100 USP sodium heparin. The initial portion of the blood was discarded to avoid contamination with mature endothelial cells from the vein wall as per the technique of Boyer et al. The blood was then mixed with an equal volume of Hank's balanced salt solution (HBSS) and mononuclear cells separated by discontinuous density gradient centrifugation (400 "g", 30 minutes). The mononuclear cell fraction was harvested and labeled with CD34+ FITC antibody. CD34+ve progenitor cells and endothelial cells were isolated by immunomagnetic separation using a paramagnetic microbead conjugated to an anti-FITC antibody (MACS VS, Miltentyi Biotec, Cologne, Germany).The total number of mononuclear cells extracted using this method was 61 10 6 (1.22 10 6 /mL of blood). The total number of cells extracted using the immunomagnetic separation system was 0.5 10 6 cells for 50 mL of blood. The purity of this sample was 6.45%, so the total number of CD34+ cells was 32,250 cells, ie, 3.2 10 4 cells per 50 mL of blood (645 cells/mL).In our experiment, we extracted 10 times more mononuclear cells than Boyer et al did. However, our total number of pure CD34+ cells was only 3.2 10 4 cells. Even if the purity were 15.7% as shown by Asahara et al, 4 then the total number of cells extracted would still be only 7.85 10 4 cells. This does not constitute a large number of cells, which can be used for single stage seeding, such as that required for polytetrafluoroethylene, where 2 10 5 cells per cm 2 for graft are needed. 5 We would also expect the number of cells that can be extracted in an older patient to be less and more likely to fail in culture. 6 Regarding the two ...
RESUMO Poeta de vanguarda que se tornou historiador e teórico da arte, mediador cultural entre França e Alemanha, Carl Einstein colaborou com diversas publicações (entre as quais Die weißen Blätter, Die Aktion, Das Kunstblatt e Transition). Foi coeditor, com Georg Grosz, de Der blutige Ernst (1919) e, com Paul Westheim, de Europa-Almanach (1925), além de cofundador da revista Documents (1929) junto com Georges Bataille, Michel Leiris, Georges Wildenstein e Georges-Henri Rivière. Pertenceu ao círculo de Daniel-Henry Kahnweiler; conheceu Pablo Picasso, Georges Braque, Juan Gris e Fernand Léger. Este artigo se propõe a apresentar algumas das particularidades da escrita e do pensamento de Carl Einstein, sua coerência intelectual, assim como familiarizar o leitor com um âmbito intelectual excepcional, através da rede de diálogos, brechas e aberturas que seus escritos apresentam.
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Protestos contra o racismo, derrubada de estatuas de traficantes de escravos, requisições e promessas de restituição de artefatos africanos aos seus países de origem por parte de museus europeus foram alguns dos eventos que tiveram lugar em 2020. Mais recentemente, vários monumentos e memoriais que valorizavam o colonialismo europeu foram vandalizados ou derrubados na Colômbia no meio de protestos contra a atual administração; o ataque ao monumento a Borba Gato no bairro de Santo Amaro em São Paulo é mais um na lista de ações contra símbolos coloniais. No contexto de persistência das doutrinas sobre desigualdades raciais, esses eventos tornam necessário pensar algumas exposições com maior profundidade. Este artigo analisa algumas exposições de “arte negra” em Nova York e Montevidéu como exemplos da construção de um olhar estetizante, nem neutro nem espontâneo. Essa perspectiva construída foi forjada no início do século 20, no contexto de uma África colonizada, por meio de ações concretas e deliberadas iniciadas por um pequeno grupo de artistas de vanguarda, críticos, colecionadores e marchands. Sua responsabilidade na escolha das obras, nas exposições que organizaram e nas obras que publicaram, aponta para uma construção do “cânone” das artes africanas que sobrevive no Ocidente até hoje.
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