Given a passage with a context and an answer, 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.

Input: Consider Input: Context: Evidence obtained from porcine cell cultures and experiments in laboratory animals indicates that transmembrane transporters may play a role in the distribution of the active morphine metabolite morphine-6-glucuronide (M6G). This was evaluated in a study in healthy volunteers.', 'Ten subjects received an intravenous M6G infusion for 30 min at a dosage of 0.5 mg/kg body weight, leading to M6G plasma concentrations approximately two to three times higher than those observed with analgesic morphine doses in subjects with normal kidney function. In a randomized, double-blind, three-way crossover fashion, subjects received 800 mg quinidine for inhibition of P-glycoprotein; 500 mg probenecid for inhibition of other transporters, including organic anion transporter peptide, multidrug resistance-related protein, and organic anion transporter families; or placebo 1 h before the start of M6G administration. Plasma concentrations of M6G and pupil size were measured for 7 h.', 'Probenecid pretreatment resulted in a decrease in the clearance of M6G from 8.3 +/- 1 l/h to 6.7 +/- 1.3 l/h (factor of 0.8; P < 0.05 vs. placebo cotreatment). This was paralleled by an increase by a factor of 1.2 of the area under the miotic effect-versus-time curves (P < 0.05 vs. placebo). In contrast, quinidine pretreatment had no influence on the pharmacokinetics of M6G.
Answer: The active morphine metabolite is subject to transmembrane transport by transporters inhibited by probenecid in humans.

Output: Does probenecid interact with the pharmacokinetics of morphine-6-glucuronide in humans?


Input: Consider Input: Context: Surfactant protein A (SP-A) is a C-type lectin involved in surfactant homeostasis as well as host defense in the lung. We have recently demonstrated that SP-A enhances the killing of bacillus Calmette-Guerin (BCG) by rat macrophages through a nitric oxide-dependent pathway. In the current study we have investigated the role of tyrosine kinases and the downstream mitogen-activated protein kinase (MAPK) family, and the transcription factor NFkappaB in mediating the enhanced signaling in response to BCG in the presence of SP-A.', 'Human SP-A was prepared from alveolar proteinosis fluid, and primary macrophages were obtained by maturation of cells from whole rat bone marrow. BCG-SP-A complexes were routinely prepared by incubation of a ratio of 20 microg of SP-A to 5 x 105 BCG for 30 min at 37 degrees C. Cells were incubated with PBS, SP-A, BCG, or SP-A-BCG complexes for the times indicated. BCG killing was assessed using a 3H-uracil incorporation assay. Phosphorylated protein levels, enzyme assays, and secreted mediator assays were conducted using standard immunoblot and biochemical methods as outlined.', 'Involvement of tyrosine kinases was demonstrated by herbimycin A-mediated inhibition of the SP-A-enhanced nitric oxide production and BCG killing. Following infection of macrophages with BCG, the MAPK family members ERK1 and ERK2 were activated as evidence by increased tyrosine phosphorylation and enzymatic activity, and this activation was enhanced when the BCG were opsonized with SP-A. An inhibitor of upstream kinases required for ERK activation inhibited BCG- and SP-A-BCG-enhanced production of nitric oxide by approximately 35%. Macrophages isolated from transgenic mice expressing a NFkappaB-responsive luciferase gene showed increased luciferase activity following infection with BCG, and this activity was enhanced two-fold in the presence of SP-A. Finally, lactacystin, an inhibitor of IkappaB degradation, reduced BCG- and SP-A-BCG-induced nitric oxide production by 60% and 80% respectively.
Answer: These results demonstrate that BCG and SP-A-BCG ingestion by macrophages is accompanied by activation of signaling pathways involving the MAP kinase pathway and NFkappaB.

Output: Are mitogen-activated protein kinases and NFkappaB involved in SP-A-enhanced responses of macrophages to mycobacteria?


Input: Consider Input: Context: To test the hypothesis that diffuse abnormalities precede axonal damage and atrophy in the MRI normal-appearing tissue of relapsing-remitting (RR) multiple sclerosis (MS) patients, and that these processes continue during clinical remission.', 'Twenty-one recently diagnosed mildly disabled (mean disease duration 2.3 years, mean Expanded Disability Status Scale score of 1.4) RR MS patients and 15 healthy matched controls were scanned with MRI and proton MR spectroscopic imaging ((1)H-MRSI) at 3 T. Metabolite concentrations: N-acetylaspartate (NAA) for neuronal integrity; choline (Cho) for membrane turnover rate; creatine (Cr) and myo-inositol (mI) for glial status were obtained in a 360 cm(3) volume of interest (VOI) with 3D multivoxel (1)H-MRSI. They were converted into absolute amounts using phantom replacement and normalised into absolute concentrations by dividing by the VOI tissue volume fraction obtained from MRI segmentation.', "The patients' mean VOI tissue volume fraction, 0.92 and NAA concentration, 9.6 mM, were not different from controls' 0.94 and 9.6 mM. In contrast, the patients' mean Cr, Cho and mI levels 7.7, 1.9 and 4.1 mM were 9%, 14% and 20%, higher than the controls' 7.1, 1.6 and 3.4 mM (p = 0.0097, 0.003 and 0.0023).
Answer: The absence of early tissue atrophy and apparent axonal dysfunction (NAA loss) in these RR MS patients suggests that both are preceded by diffuse glial proliferation (astrogliosis), as well as possible inflammation, demyelination and remyelination reflected by elevated mI, Cho and Cr, even during clinical remission and despite immunomodulatory treatment.


Output: Does mR spectroscopy indicate diffuse multiple sclerosis activity during remission?