TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Enterovirus infections are major etiological factors in myocarditis and dilated cardiomyopathy. Using an experimental murine model of this disease, previous studies have shown that myocarditis susceptibility depends upon activation of T lymphocytes expressing the gamma delta T cell receptor (TcR), and that only mouse strains which accumulate gamma delta T cells in the myocardium show apoptosis of myocytes or evidence of dilated cardiomyopathy-like disease. The objective of the present studies is to demonstrate that gamma delta T cells directly induce greater Fas-dependent apoptosis of cultured myocytes than T cells expressing the alpha beta TcR.', 'Bl.Tg.E alpha mice were infected for 7 days with coxsackievirus B3 (CVB3). Hearts were removed and were either formalin-fixed, sectioned and stained with hematoxylin and eosin for inflammation, and using TdT-TUNEL for apoptosis, or were minced and collagenase digested for isolation of gamma delta+ and alpha beta+ T cells using immunomagnetic bead separation. Neonatal cultures of cardiac myocytes were isolated from mice less than 2 days old by collagenase and pancreatin digestion, and were either untreated or infected with virus. Levels of Fas (CD95) were measured using FITC-conjugated hamster anti-mouse Fas monoclonal antibody and flow cytometry. Susceptibility of myocytes to Fas-dependent killing was measured by 51Cr-release by labeled myocytes incubated for 4 h on either 3T3-mock or 3T3-FasL transfected cell monolayers. Killing by T cells was also measured in a 4 h 51Cr-release assay. Fas-dependent and perforin-dependent cytotoxicity was determined by specific blocking using either Fas-Fc or concanamycin A.', 'Virally infected myocyte cultures showed significantly enhanced Fas expression compared to uninfected cells, with maximal upregulation of Fas occurring 18-24 h after virus infection. Both infected and uninfected myocytes were selectively killed by FasL-transfected 3T3 cells but not by mock control cells. Approximately 38% of CD3+ lymphocytes isolated from the heart express the gamma delta TcR with the remainder expressing the alpha beta TcR. Both gamma delta+ and alpha beta+ T cells lysed myocyte targets. Blocking studies indicate that gamma delta+ T cells induced predominantly Fas-mediated killing, while alpha beta+ cell produced more perforin-mediated death, although these effectors were capable of Fas-dependent killing as well.\Question: Do t cells expressing the gamma delta T cell receptor induce apoptosis in cardiac myocytes?

SOLUTION: These studies demonstrate that T cells expressing the gamma delta TcR are more effective mediators of myocyte apoptosis than alpha beta+ T cells in vitro and suggests that these effectors may be primarily responsible for myocardial injury associated with dilated cardiomyopathy-like signs during coxsackievirus B3-induced myocarditis.

PROBLEM: Context: Extracellular histones exert part of their prothrombotic activity through the stimulation of blood cells. Besides platelets, histones can bind to red blood cells (RBCs), which are important contributors to thrombogenesis, but little is known about the functional consequences of this interaction.', 'To evaluate the effect of histones on the procoagulant potential of human RBCs with particular regard to the expression of surface phosphatidylserine (PS).', 'PS exposure on human RBCs treated with a natural mixture of histones or recombinant individual histones was evaluated with fluorescein isothiocyanate-annexin-V binding and measured with flow cytometry. Calcium influx in RBCs loaded with the calcium-sensitive fluorophore Fluo-4AM was assessed with flow cytometry. The procoagulant potential of histone-treated RBCs was evaluated with a purified prothrombinase assay and a one-stage plasma recalcification clotting test.', 'Natural histones induced PS exposure on RBCs in a dose-dependent manner, and neutralization or cleavage of histones by heparin or activated proteinC, respectively, abolished PS externalization. H4 was mainly responsible for the stimulating activity of histones, whereas the other subtypes were almost ineffective. Similarly, natural histones and H4 induced influx of calcium into RBCs, whereas the other individual histones did not. Histone-induced exposure of PS on RBCs translated into increased prothrombinase complex-mediated prothrombin activation and accelerated fibrin formation in plasma.\Question: Do histones induce phosphatidylserine exposure and a procoagulant phenotype in human red blood cells?

SOLUTION: Histones induce RBCs to express a procoagulant phenotype through the externalization of PS. This finding provides new insights into the prothrombotic activity of extracellular histones.

PROBLEM: Context: We aimed to investigate whether and how the total flavonoid extracts (TFE) from Inula britannica L. block neointimal hyperplasia induced by balloon injury in rats.', 'Rats were administered orally TFE doses of 12.5, 25 and 50 mg/kg/d by gastric gavage from 3 days before balloon injury to 14 days after the injury. The ratio of intima (I) to media (M) thickness (I/M) in carotid arteries was examined by morphological analyses. The MDA content and SOD activity in plasma were measured. The O(2)(-) production in vascular tissues was detected in situ. The expression of p47(phox) in carotid arteries was analyzed by Western blot analysis and immunohistochemistry.', 'The rats treated with TFE 50 mg/kg/d showed a reduction in neointimal hyperplasia, and the ratio of I/M of balloon injured-carotid arteries was significantly reduced by over 70% after TFE treatment, compared with the injured group. The inhibitory effect of TFE on neointimal hyperplasia was almost consistent with that of atorvastatin, a positive control. The plasma SOD activity was obviously increased by TFE treatment (P<0.01), while plasma MDA production was markedly decreased by TFE treatment (P<0.05). On day 14 after balloon injury, the carotid arteries showed an increase in O(2)(-) production that was most evident in the neointimal and medial layer of the vessel. Thus, TFE significantly inhibited injury-induced O(2)(-) production and p47(phox) expression in carotid arteries.\Question: Do flavonoids from Inula britannica L. inhibit injury-induced neointimal formation by suppressing oxidative-stress generation?

SOLUTION:
Our results suggest that TFE inhibit the neointimal hyperplasia after balloon injury, at least partly, by suppressing oxidative-stress generation.