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.
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Question: Large concentrations of meperidine inhibit N-methyl-D-aspartate-(NMDA) receptor channels by channel block mechanisms. Extracellular pH regulates the activity and drug sensitivity of NMDA-receptor channels. We examined the influence of extracellular pH on sensitivity to meperidine of epsilon/zeta heteromeric NMDA-receptor channels expressed in Xenopus oocytes. Inhibition of epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1, and epsilon4/zeta1 channels by meperidine was dependent on pH, with more inhibition at acidic pH and less inhibition at alkaline pH. The degree of voltage-dependence of meperidine block was only slightly affected by changes in pH, whereas affinity for meperidine was greatly reduced at alkaline pH. Furthermore, interaction of meperidine with Mg(2+) block was reduced at alkaline pH. Because the percentage of the protonated form of meperidine is only slightly affected by pH, changes in properties of the meperidine binding site may be involved in mechanisms of alteration of meperidine potency by pH.

Answer: Is n-methyl-D-aspartate receptor channel block by meperidine dependent on extracellular pH?


Question: To investigate B7-H4 expression and its correlation with the number of infiltrating T lymphocytes and cytokine production by those lymphocytes in human cervical cancer and to determine the effect of recombinant B7-H4 on the active peripheral blood T cells of the patients in vitro.', 'B7-H4 expression was detected in 67 cases of cervical cancer using immunohistochemical staining. Tumor-infiltrating CD8(+)T, CD4(+)T, and FOXP3(+) (Forkhead Box P3) T lymphocytes and their levels of IFN-γ and TGF-β₁ production were determined by immunofluorescent double-staining. After the peripheral blood T lymphocytes of patients were co-cultured with B7-H4, proliferation, apoptosis, and cell subtypes were analyzed using flow cytometry. Cytokines in the supernatant were detected by ELISA.', "B7-H4 was expressed in 46% (31/67) of the cases of cervical cancer. The number of infiltrating CD8(+)T lymphocytes and their IFN-γ production in positive B7-H4 expression cervical cancers was significantly lower than in negative B7-H4 cases (P<0.01, P<0.05), but there was no significant difference between cases positive and negative for B7-H4 with respect to infiltrating FOXP3(+)T and CD4(+)T cells or TGF-β1 production. After co-culture with B7-H4 for 48 h, the patients' activated T lymphocytes were arrested at G1/G2 phase. The Ki67 positive rates of CD4(+)T and CD8(+)T cells were 2.13 ± 0.13% and 1.03 ± 1.33%, and they were lower than in the blank group. The proportion of CD4(+)T and CD8(+)T cells decreased, but CD4(+)T/CD8(+)T and the proportion of CD4(+)CD25(+)Foxp3(+)T cells increased. In addition, concentrations of IL-10 and TGF-β1 in the supernatant of co-cultured T cells increased significantly (P<0.05, P<0.05), but that of IFN-γ decreased. B7-H4 had no significant effect on apoptosis of the T cells.

Answer: Does b7-H4 overexpression impair the immune response of T cells in human cervical carcinomas?


Question: X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) is a novel tumor suppressor and interferon (IFN)-stimulated gene. All-trans retinoic acid (ATRA) exerts an antiproliferative effect on tumor cells through up-regulation of IFN regulatory factor 1 (IRF-1) and the downstream IFN-stimulated genes. The aim of this study was to determine the effect and mechanism of ATRA on XAF1 expression and the role of XAF1 in ATRA-induced growth inhibition in colon cancer.', 'Gene expression is detected by reverse-transcription polymerase chain reaction and immunoblotting. The transcription activity of XAF1 promoter is examined by luciferase reporter assay. The activity of IFN regulatory factor binding element (IRF-E) is assessed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Cell growth is evaluated by both in vitro and in vivo in nude mice xenografts.', 'IFN-alfa stimulates XAF1 promoter activity in the colon cancer cells Lovo and SW1116 dose-dependently. An IRF-1 binding element (IRF-E-XAF1) is found in the -30 to -38 nucleotide region upstream of the ATG initiator codon of the XAF1 gene. Site-directed mutagenesis of IRF-E-XAF1 abrogates native and IFN-induced promoter activity and binding capacity. ATRA induces XAF1 expression both in vitro and in vivo through interaction with IRF-E-XAF1. Overexpression of XAF1 increases cell susceptibility to ATRA-induced growth suppression both in vitro and in vivo. Furthermore, the effect of ATRA on XAF1 expression is independent of the promoter methylation and the subcellular distribution of XIAP.

Answer:
Does all-trans retinoic acid induce XAF1 expression through an interferon regulatory factor-1 element in colon cancer?