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.
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Question: Context: Tumor necrosis factor-alpha (TNF-alpha) is a major pro-inflammatory cytokine. Recently, the G-308A polymorphism of the TNF-alpha gene has been associated with modified gene expression and increased TNF-alpha production in the -308A allele. We evaluated its influence on the incidence and clinical course of membranous glomerulonephritis.', 'We studied 53 patients with biopsy-proven primary membranous glomerulonephritis followed up for 5.7 +/- 4.9 years. 100 volunteers were analyzed as controls. According to the slope of the curve of reciprocal serum creatinine against time, group A (slow progressors, n = 35) and group B (fast progressors, n = 18) were defined. TNF-alpha G-308A polymorphism was determined by polymerase chain reaction amplification.', 'The frequency of the A-allele (associated with higher TNF-alpha levels) was significantly higher in patients than control subjects (patients: G-allele: 0.66, A-allele: 0.34; controls: G-allele 0.85, A-allele 0.15, p < 0.001). Similarly, the genotype distribution differed significantly between our study and control populations (patients: GG-genotype: 41.5%, GA: 49.1%, AA 9.4%; controls: GG: 71%, GA: 27%, AA 2%, p = 0.001). Age, renal function, proteinuria and blood pressure were similar at the time of renal biopsy between patients with different genotypes (NS). There was also a tendency towards an overpresentation of the A-allele in group B indicating a possible impact on the progression of membranous nephropathy, but a significance was not reached. Furthermore, no impact on renal survival in the Kaplan- Meier analysis was detected (NS).
Answer: Our results suggest that TNF-alpha gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis.

Answer: Is tumor necrosis factor-alpha gene G-308A polymorphism a risk factor for the development of membranous glomerulonephritis?


Question: Context: Surfactant protein (SP) D shares target cells with the proinflammatory cytokine TNF-alpha, an important autocrine stimulator of dendritic cells and macrophages in the airways.', 'We sought to study the mechanisms by which TNF-alpha and SP-D can affect cellular components of the pulmonary innate immune system.', 'Cytokine and SP-D protein and mRNA expression was assessed by means of ELISA, Western blotting, and real-time PCR, respectively, by using in vivo models of allergic airway sensitization. Macrophage and dendritic cell phenotypes were analyzed by means of FACS analysis. Maturation of bone marrow-derived dendritic cells was investigated in vitro.', 'TNF-alpha, elicited either by allergen exposure or pulmonary overexpression, induced SP-D, IL-13, and mononuclear cell influx in the lung. Recombinant IL-13 by itself was also capable of enhancing SP-D in vivo and in vitro, and the SP-D response to allergen challenge was impaired in IL-13-deficient mice. Allergen-induced increase of SP-D in the airways coincided with resolution of TNF-alpha release and cell influx. SP-D-deficient mice had constitutively high numbers of alveolar mononuclear cells expressing TNF-alpha, MHC class II, CD86, and CD11b, characteristics of proinflammatory, myeloid dendritic cells. Recombinant SP-D significantly suppressed all of these molecules in bone marrow-derived dendritic cell cultures.
Answer: TNF-alpha can contribute to enhanced SP-D production in the lung indirectly through inducing IL-13. SP-D, on the other hand, can antagonize the proinflammatory effects of TNF-alpha on macrophages and dendritic cells, at least partly, by inhibiting production of this cytokine.

Answer: Does surfactant protein D inhibit TNF-alpha production by macrophages and dendritic cells in mice?


Question: Context: Multidrug resistance (MDR) has a potentially serious influence on cancer treatment and should be taken into consideration in the design and application of therapeutic regimens. It is mediated through the activity of cellular pumps.', 'To investigate whether furosemide, itself a pump-blocker, reverses MDR in an in vitro model.', 'An MDR bladder cancer cell line (MGH-u 1R) and its parental (drug sensitive) clone were exposed to epirubicin and furosemide, with the concentration of one drug fixed and that of the other serially diluted in a 96-well plate format. Both drugs formed the variable component in separate experiments. After a 1-h exposure, the cells were washed and replenished with fresh medium. To examine the toxicity of epirubicin and furosemide separately and in combination, monotetrazolium-based assays were carried out. Intracellular epirubicin distribution was assessed by confocal microscopy as a second index of resistance status after in vitro exposure.', 'MGH-u 1R cells incubated with furosemide showed distribution of drug similar to that in the parental cells (MGH-u 1 sensitive). Controls (without furosemide) continued to show a resistant pattern of fluorescence. In cytotoxicity assays furosemide appeared substantially non-toxic. Resistant cells in the toxicity titration experiments showed increased resistance to levels of furosemide over 500 mug/ml. Parental cells were made only marginally more sensitive against increased background toxicity.
Answer: Furosemide is effective in reversing MDR status in bladder cancer cell lines in vitro. It may also have an increment of intrinsic cytotoxicity, but only at higher concentrations. We propose a potential for further investigation of furosemide as an adjunct to chemotherapy for superficial bladder cancer.

Answer:
Does furosemide reverse multidrug resistance status in bladder cancer cells in vitro?