TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: GM-CSF has broad clinical applicability as a potent myelopoietic stimulator. However, its function is not restricted to the myelopoietic system and several observations suggest that GM-CSF may interfere with the hemostatic balance. In order to assess whether GM-CSF has any influence on hemostasis, we evaluated some coagulative and fibrinolytic parameters in patients treated with GM-CSF following chemotherapy.', 'Fibrinolytic activity (FA), fibrinogen and D-dimer were evaluated before and after high-dose cyclophosphamide in 6 patients additionally treated with GM-CSF and in 5 control patients; moreover, tissue plasminogen activator (tPA) was assayed in those treated with GM-CSF. Comparative in vitro analysis was performed on cultured endothelial cells before and after exposure to GM-CSF.', 'Control patients showed a significant decrease in plasma FA after chemotherapy compared to basal values (FA/mm2: 15.6 +/- 2.1 at day + 2 and 20.8 +/- 19 at day + 4 vs. 103.8 +/- 64.2 at day 0; p < 0.005); conversely, no FA reduction was observed in GM-CSF-treated subjects. In this latter group a marked increase in tPA antigen was seen, consistent with enhanced FA. No significant changes in plasma D-dimer and fibrinogen values were detected in the two groups. tPA, urokinase-type plasminogen activator, PAI-1 and procoagulant activity were evaluated in vitro on cultured human endothelial cells and found to be unchanged following GM-CSF addition.

SOLUTION: Is reduction of plasma fibrinolytic activity following high-dose cyclophosphamide neutralized in vivo by GM-CSF administration?

PROBLEM: The relationship of bipolar disorder (BD) and altered thyroid function is increasingly recognized. Recently, a behavioral phenotype of co-occurring deviance on the Anxious/Depressed (A/D), Attention Problems (AP), and Aggressive Behavior (AB) syndrome scales has been identified as the Child Behavior Checklist Dysregulation Profile (CBCL-DP), which itself has been linked to BD. This study tested for differences in thyroid function within a sample of n=114 psychiatric children and adolescents with and without the CBCL-DP.', 'A CBCL-DP score was generated based on the composite of the crucial CBCL syndrome scales (A/D, AP, AB). Participants with a CBCL-DP score >or=2.5 SDs above average constituted the CBCL-DP subgroup (n=53). Those with CBCL-DP scores of 1 SD or less above average percentile were regarded as controls (n=61). Groups were compared regarding serum levels of TSH, fT3 and fT4.', 'In participants showing the CBCL-DP, basal serum TSH was elevated compared to controls. More CBCL-DP subjects than controls showed subclinical hypothyroidism. No differences were observed for serum fT3 and fT4 levels.

SOLUTION: Is severe affective and behavioral dysregulation in youth associated with increased serum TSH?

PROBLEM: Human ZR75-1 cells were among the first few characterized estrogen-dependent mammary gland carcinoma cell lines and had been utilized in various studies for the pro- or antitumor effect of xenoestrogens and antiestrogens. The objective of this study was to establish a breast tumor model in ZR75-1 cells bearing multimodal reporter genes to allow noninvasive imaging of tumor growth using fluorescence and nuclear imaging platforms.', 'Enhanced green fluorescent protein (eGFP) cDNA was fused at the C-terminus with herpes simplex virus type 1 thymidine kinase (HSV1-tk) to form the fusion reporter gene (eGFP-tk). In vitro proliferation, migration, and invasion assays revealed that eGFP-tk-transfected ZR75-1 cells exhibited decreased proliferation rate, migratory activity, and invasion ability compared to the wild-type cells. The functional HSV1-tk enzymatic activity in stably transfected cells were confirmed by in vitro ganciclovir (GCV) sensitivity and [123I]2-fluoro-2-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil (FIAU) accumulation assays. In vivo fluorescence and nuclear imaging were performed on nude mice bearing multiple subcutaneous xenografts established from ZR75-1-eGFP-tk and wild-type cells. Optical imaging was able to detect the green fluorescence of eGFP-tk tumor. The eGFP-tk reporter gene-specific imaging was achieved by single photon emission computed tomography (SPECT) using [123I]FIAU as a radiotracer and demonstrated decreased FIAU uptake in eGFP-tk tumor by GCV treatment. Probably due to a flare reaction after GCV treatment, micro-positron emission tomography (micro-PET) imaging using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) could not demonstrate decreases in FDG uptake. However, in vitro metabolic assay also revealed that eGFP-tk cells transiently increased [3H]-deoxyglucose uptake in response to GCV treatment.

SOLUTION:
Do human breast tumor cells express multimodal imaging reporter genes?