Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms leading to a relative dominance of T cells producing type 2 cytokines in certain human immune disorders are still unclear. We investigated the relative susceptibility to apoptosis induced by primary in vitro activation of human type 1 (producing interferon-gamma (IFN-gamma)) or type 2 (producing IL-4) T cells. Peripheral blood lymphocytes were isolated from patients with immune disorders characterized by expansion of type 2 cells (four with AIDS and hyper-IgE/hypereosinophilia, one with Churg-Strauss syndrome, and one with idiopathic hypereosinophilic syndrome) or from individuals with normal cytokine balances. Cells were stimulated for 16 h with ionomycin and phorbol ester, and apoptosis of cytokine-producing cells was assessed by flow cytometry. T cells with a type-2 cytokine profile, i.e. producing IL-4 alone, were significantly more resistant to activation-induced apoptosis than those producing IFN-gamma alone. This was observed in AIDS patients, whose type 2 cells were mostly CD8+, as well as in the patients with Churg-Strauss and with hypereosinophilic syndrome. CD4+ and CD8+ IL-4-producing cells were equally resistant to apoptosis. Lower susceptibility to apoptosis of type-2 T cells was also observed in subjects with normal cytokine balances. Bcl-2 expression was high in type-2 cells and in viable type-1 cells, whereas it was low in apoptotic type-1 cells. Resistance to activation-induced apoptosis may explain the expansion of cells producing type-2 cytokines in certain immune disorders.
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PMID:Human T cells with a type-2 cytokine profile are resistant to apoptosis induced by primary activation: consequences for immunopathogenesis. 1084 23

Hypereosinophilic syndrome (HES) has recently been recognized as a clonal leukemic lesion, which is due to a specific oncogenic event that generates hyperactive platelet-derived growth factor receptor-alpha-derived tyrosine kinase fusion proteins. In the present work, the effect of retinoids on the leukemic hypereosinophilia-derived EoL-1 cell line and on primary HES-derived cells has been investigated. We show that all-trans-retinoic acid (ATRA) inhibits eosinophil colony formation of HES-derived bone marrow cells and is a powerful inducer of apoptosis of the EoL-1 cell line. Apoptosis was shown in the nanomolar concentration range by phosphatidylserine externalization, proapoptotic shift of the Bcl-2/Bak ratio, drop in mitochondrial membrane potential, activation of caspases, and cellular morphology. Unlike in other ATRA-sensitive myeloid leukemia models, apoptosis was rapid and was not preceded by terminal cell differentiation. Use of isoform-selective synthetic retinoids indicated that retinoic acid receptor-alpha-dependent signaling is sufficient to induce apoptosis of EoL-1 cells. Our work shows that the scope of ATRA-induced apoptosis of malignancies may be wider within the myeloid lineage than thought previously, that the EoL-1 cell line constitutes a new and unique model for the study of ATRA-induced cell death, and that ATRA may have potential for the management of clonal HES.
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PMID:Apoptosis induction by retinoids in eosinophilic leukemia cells: implication of retinoic acid receptor-alpha signaling in all-trans-retinoic acid hypersensitivity. 1677 11

Fluid resuscitation is vital for treating traumatic hemorrhagic shock (HS), but reperfusion is believed to have the adverse consequences of generating reactive oxygen species and inflammatory cytokines, both of which cause multiple organ dysfunctions. We investigated the effects of various resuscitation fluids on the changes of redox-sensitive molecules after HS and fluid resuscitation (HS/R). We induced HS by bleeding male Sprague-Dawley rats to a blood pressure of 30 to 40 mmHg for 60 minutes. Thirty minutes later, the rats were killed (HS group) or immediately resuscitated with shed blood (HS + BL group), L-isomer lactated Ringer's solution (HS + LR group), or hydroxyethyl starch (HS + HES group). After HS, we found a significant increase in nuclear factor kappaB DNA binding activity, which was effectively inhibited using HES solution or blood resuscitation. Moreover, resuscitation with blood or LR solution, but not HES solution, induced significant oxidative stress, manifested by a high ratio of oxidized glutathione to reduced glutathione in the lungs, liver, and spleen. HS alone, however, did not increase the ratio of the oxidized glutathione to reduced glutathione in all organs. Although the protein expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax varied in different organs, we found that resuscitation using HES solution prevented the HS-induced reduction of the Bcl-2/Bax ratio in the heart. HES solution was an appropriate resuscitation fluid in reversing nuclear factor kappaB activation, maintaining the Bcl-2/Bax ratio, and preventing oxidative stress after acute HS.
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PMID:Resuscitation with hydroxyethyl starch solution prevents nuclear factor kappaB activation and oxidative stress after hemorrhagic shock and resuscitation in rats. 1743 58