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: Downstream effects of muscarinic receptor stimulation in intestinal smooth muscle include contraction and intestinal transit. We thought to determine whether classic transient receptor potential (TRPC) channels integrate the intracellular signaling cascades evoked by the stimulated receptors and thereby contribute to the control of the membrane potential, Ca-influx, and cell responses.', 'We created trpc4-, trpc6-, and trpc4/trpc6-gene-deficient mice and analyzed them for intestinal smooth muscle function in vitro and in vivo.', 'In intestinal smooth muscle cells TRPC4 forms a 55 pS cation channel and underlies more than 80% of the muscarinic receptor-induced cation current (mI(CAT)). The residual mI(CAT) depends on the expression of TRPC6, indicating that TRPC6 and TRPC4 determine mI(CAT) channel activity independent of other channel subunits. In TRPC4-deficient ileal myocytes the carbachol-induced membrane depolarizations are diminished greatly and the atropine-sensitive contraction elicited by acetylcholine release from excitatory motor neurons is reduced greatly. Additional deletion of TRPC6 aggravates these effects. Intestinal transit is slowed down in mice lacking TRPC4 and TRPC6.
Answer: In intestinal smooth muscle cells TRPC4 and TRPC6 channels are gated by muscarinic receptors and are responsible for mI(CAT). They couple muscarinic receptors to depolarization of intestinal smooth muscle cells and voltage-activated Ca(2+)-influx and contraction, and thereby accelerate small intestinal motility in vivo.

Output: Does deletion of TRPC4 and TRPC6 in mice impair smooth muscle contraction and intestinal motility in vivo?

Input: Consider Input: Context: Intestinal ischemia/reperfusion (I/R) injury is believed to be the major initiator of the systemic inflammatory response syndrome. As a result of intestinal I/R, the gut becomes a major source of inflammatory cytokine production. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) is cytoprotective after intestinal I/R and down-regulates pro-inflammatory cytokine production in vitro. We now examine the effects of HB-EGF on pro-inflammatory cytokine expression in vivo.', 'Rats were randomized into three groups: sham-operated, superior mesenteric artery occlusion (SMAO) for 90 min followed by 8 h of reperfusion (I/R), and I/R with intraluminal administration of HB-EGF 25 min after the initiation of ischemia (I/R + HB-EGF). Serum was drawn at 2, 4, 6, and 8 h post reperfusion for determination of cytokine protein levels using a bioplex suspension array system. Additional animals underwent the same ischemic protocol followed by 30 and 60 min of reperfusion with harvesting of ileal mucosa. Ileal pro-inflammatory cytokine gene expression was determined using reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for TNF-alpha, IL-6, and IL-1beta.', 'HB-EGF decreased TNF-alpha, IL-6, and IL-1beta serum protein levels at 4, 6, and 8 h after intestinal I/R injury. In addition, HB-EGF decreased local intestinal mucosal mRNA expression of TNF-alpha, IL-6, and IL-1beta 30 and 60 min after intestinal injury.
Answer: We conclude that pro-inflammatory cytokine expression is increased both locally and in the systemic circulation after intestinal I/R and that the administration of HB-EGF significantly reduces intestinal I/R-induced pro-inflammatory cytokine expression in vivo.

Output: Does heparin-binding EGF-like growth factor decrease inflammatory cytokine expression after intestinal ischemia/reperfusion injury?

Input: Consider Input: Context: To examine a population-based cohort for the association between clinicopathologic predictors of survival and immunohistochemical markers (IHC), and to assess changes in gene expression that are associated with lymphovascular invasion (LVI).', 'LVI has been associated with poor survival and aggressive tumor behavior. The molecular changes responsible for the behavior of gastric cancer have yet to be determined. Characterization of IHC markers and gene expression profiles may identify molecular alterations governing tumor behavior.', ': Clinicopathologic and survival data of 114 patients were reviewed. Archival specimens were used to construct a multitumor tissue array that was subjected to IHC of selected protein targets. Correlation of IHC with tumor thickness (T status), LVI and prognosis was studied. Microarray analysis of fresh gastric cancer tissue was conducted to examine the gene expression profile with respect to LVI.', 'In a multivariate analysis, nodal status (N), metastasis (M), and LVI were independent predictors of survival. LVI was associated with a 5-year survival of 13.9% versus 55.9% in patients in whom it was absent. LVI correlated with advancing T status (P = 0.001) and N status (P < 0.001). IHC staining of cyclooxygenase-2 (COX-2) correlated with T status, tumor grade, lymph node positivity, and IHC staining of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). Microarray analyses suggested differential expression of oligophrenin-1 (OPHN1) and ribophorin-II (RPNII) with respect to LVI.
Answer: LVI was an independent predictor of survival in gastric cancer. Expression of COX-2 may facilitate tumor invasion through MMP-2 and MMP-9 activation. OPHN1 and RPN II appeared to be differentially expressed in gastric cancers exhibiting LVI. The reported function of OPHN1 and RPN II makes these gene products promising candidates for future studies involving LVI in gastric cancer.
Output: Is lymphovascular invasion associated with poor survival in gastric cancer : an application of gene-expression and tissue array techniques?