Understanding discourse-linked elements in aphasia: a threefold study in Russian.

BACKGROUND: Agrammatic speakers have problems with grammatical encoding and decoding. However, not all syntactic processes are equally problematic: present time reference, who questions, and reflexives can be processed by narrow syntax alone and are relatively spared compared to past time reference, which questions, and personal pronouns, respectively. The latter need additional access to discourse and information structures to link to their referent outside the clause (Avrutin, 2006). Linguistic processing that requires discourse-linking is difficult for agrammatic individuals: verb morphology with reference to the past is more difficult than with reference to the present (Bastiaanse et al., 2011). The same holds for which questions compared to who questions and for pronouns compared to reflexives (Avrutin, 2006). These results have been reported independently for different populations in different languages. The current study, for the first time, tested all conditions within the same population. AIMS: We had two aims with the current study. First, we wanted to investigate whether discourse-linking is the common denominator of the deficits in time reference, wh questions, and object pronouns. Second, we aimed to compare the comprehension of discourse-linked elements in people with agrammatic and fluent aphasia. METHODS AND PROCEDURES: Three sentence-picture-matching tasks were administered to 10 agrammatic, 10 fluent aphasic, and 10 non-brain-damaged Russian speakers (NBDs): (1) the Test for Assessing Reference of Time (TART) for present imperfective (reference to present) and past perfective (reference to past), (2) the Wh Extraction Assessment Tool (WHEAT) for which and who subject questions, and (3) the Reflexive-Pronoun Test (RePro) for reflexive and pronominal reference. OUTCOMES AND RESULTS: NBDs scored at ceiling and significantly higher than the aphasic participants. We found an overall effect of discourse-linking in the TART and WHEAT for the agrammatic speakers, and in all three tests for the fluent speakers. Scores on the RePro were at ceiling. CONCLUSIONS: The results are in line with the prediction that problems that individuals with agrammatic and fluent aphasia experience when comprehending sentences that contain verbs with past time reference, which question words and pronouns are caused by the fact that these elements involve discourse linking. The effect is not specific to agrammatism, although it may result from different underlying disorders in agrammatic and fluent aphasia.

Cyclosporin A effects during primary and secondary activation of human umbilical cord blood T lymphocytes.

OBJECTIVE: Cyclosporin A (CsA), effective in prophylaxis and treatment of graft-vs-host disease (GVHD) after human allogeneic transplantation, blunts T-cell responses by inhibiting nuclear factor of activated T cells-1 (NFAT1) activation. This laboratory has shown that NFAT1 protein expression is severely reduced in human UCB (umbilical cord blood) T cells. Since UCB is increasingly used as a hematopoietic stem cell source in allogeneic transplantation, it is important to determine whether CsA sensitivity in UCB differs from that of adult T cells. METHODS: Surface flow cytometric analysis, intracellular cytokine staining, flow cytometric analysis of cell death, and thymidine incorporation were used in this study to determine T-cell activation and effector functions during primary and secondary stimulation in the presence of CsA. RESULTS: Although we observed differential CsA sensitivity of T-cell activation marker (CD69, CD45RO, CD25) upregulation comparing UCB and adult, we did not observe any significant difference in CsA sensitivity of T-cell effector functions. Importantly, we observed reduced IFN-gamma and TNF-alpha expression in UCB T cells both in primary and secondary stimulation, as well as increased rates of activation-induced cell death (AICD). CONCLUSION: Thus, our studies do not support the previous hypothesis that reduced GVHD observed after UCB transplantation is attributable to increased CsA sensitivity of UCB T cells. Rather, reduced UCB T-cell cytokine production and increased AICD may be important cellular mechanisms underlying these favorable rates of GVHD in UCB transplant recipients.

Reduced NFAT1 protein expression in human umbilical cord blood T lymphocytes.

Umbilical cord blood (UCB) stem cells from related and unrelated allogeneic donors have emerged as novel treatment for patients with hematologic malignancies. The incidence and severity of acute graft-versus-host disease (GVHD) after UCB transplantation compares favorably with that observed in recipients of matched unrelated donor allogeneic grafts, but remains a major cause of morbidity and mortality. It has been shown that stimulated lymphocytes from UCB have reduced production of cytokines including interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), which play a role in GVHD pathophysiology. We investigated the molecular mechanisms underlying this reduced cytokine production by analyzing expression of nuclear factor of activated T cells-1 (NFAT1) in UCB T cells. We detected no constitutive expression of NFAT1 protein in unstimulated UCB T cells compared with adult T cells. Moreover, although NFAT1 expression in UCB T cells was upregulated after prolonged (40 hours) T-cell stimulation, it was only partially upregulated when compared with adult controls. Our observation of minimal NFAT1 expression after stimulation correlated with reduced cytoplasmic IFN-gamma and TNF-alpha production in UCB T cells studied simultaneously. Reduced NFAT1 expression may blunt amplification of donor UCB T-cell alloresponsiveness against recipient antigens, thereby potentially limiting GVHD incidence and severity after allogeneic UCB transplantation.