Post-operative corticosteroid irrigation for chronic rhinosinusitis after endoscopic sinus surgery: A meta-analysis.

BACKGROUND: Recently, topical steroid therapy delivery using high-volume sinonasal irrigations has been used more frequently, following endoscopic sinus surgery (ESS), to improve drug delivery into the paranasal sinuses. OBJECTIVE: The goal of this study was to perform a systematic review with meta-analysis of the efficacy of steroid nasal irrigation on post-operative management of Chronic rhinosinusitis (CRS) following ESS. METHODS: Five databases (PubMed, SCOPUS, Embase, Web of Science, and the Cochrane database) from inception to March 2017 were independently reviewed by two researchers. Studies that scored CRS endoscopic findings and CRS-related quality of life (QOL) post-operatively before and after steroid nasal irrigation and that compared the effects of steroid nasal irrigation (treatment groups) with saline alone irrigation (control group) were included in the analysis. RESULTS: Twelve studies (n = 360) met inclusion criteria. Steroid nasal irrigation significantly reduced the endoscopic score compared with pre-treatment values and also improved QOL. Adverse effects following steroid nasal irrigation such as increased intraocular pressure (IOP) and hypothalamus-pituitary-adrenal (HPA) axis disturbance were not significant. However, compared with saline alone irrigation, the additional effects of steroid irrigation were not significant in the view of the endoscopic score and disease-specific QOL. CONCLUSION: Although steroid nasal irrigation would not induce adverse effects related to systemic steroid absorption, the beneficial effects of additional steroids in saline irrigation were ambiguous in regard to endoscopic score and CRS-related QOL improvement compared with saline alone irrigation. However, further clinical trials with robust research methodologies should be conducted to confirm the results of this study.

Transcriptional repression of RUNX2 is associated with aggressive clinicopathological outcomes, whereas nuclear location of the protein is related to metastasis in prostate cancer.

BACKGROUND: Runt-related transcription factor 2 (RUNX2) is a transcription factor that is closely related to bone formation, and prostate cancer (CaP) is the most common cancer to metastasize to bone. The present study investigated the expression levels of RUNX2 in human prostate tissue, and the correlation between RUNX2 levels and the clinicopathological characteristics of CaP. METHODS: A case-control study was conducted including 114 cases of newly diagnosed CaP and 114 age-matched BPH patients as controls. RUNX2 expression was estimated using real-time PCR and immunohistochemical staining. RESULTS: The mRNA expression of RUNX2 did not differ between CaP tissues and non-cancer BPH controls (P=0.825). However, RUNX2 expression was significantly decreased in patients with elevated PSA levels (≥20 ng ml(-1)), a Gleason score ≥8 and metastatic disease compared to those with low PSA, low Gleason score and non-metastatic disease (P=0.023, 0.005 and 0.014, respectively). Immunohistochemical analysis showed that 65.2% of the patients with positive RUNX2 nuclear staining had metastatic disease, which was present in only 25.9% of those with negative staining (P=0.010). CONCLUSIONS: RUNX2 mRNA expression was negatively correlated with CaP aggressiveness. Moreover, the nuclear location of RUNX2 may be a prognostic marker of metastasis in CaP.

Predictive value of intra-amniotic and serum markers for inflammatory lesions of preterm placenta.

OBJECTIVE: To compare the relative predictive values of amniotic fluid (AF) matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and serum C-reactive protein (CRP) for histologic chorioamnionitis and intra-amniotic infection in women with preterm labor or preterm premature rupture of membranes (PROM). STUDY DESIGN: This retrospective cohort study included 99 consecutive women with preterm labor or preterm PROM (21-35 weeks' gestation) who delivered within 72 h of transabdominal amniocentesis. The AF was cultured for aerobic and anaerobic bacteria and for genital mycoplasmas and was assayed for MMP-9 and IL-6 levels. Maternal serum CRP was measured immediately after amniocentesis. The placentas were examined histologically. MAIN OUTCOME MEASURES: histologic chorioamnionitis and intra-amniotic infection. RESULTS: The prevalence of histologic chorioamnionitis and a positive AF culture was 44% (44/99) and 28% (28/99), respectively. In predicting intra-amniotic infection, AF MMP-9 had a significantly higher area under the curve (AUC: 0.94 [95% CI, 0.87-0.98]) than AF IL-6 (0.87 [95% CI, 0.78-0.84]; P < 0.05) and serum CRP (0.76 [95% CI, 0.66-0.84]; P < 0.001) and a higher sensitivity and specificity than serum CRP (P < 0.01, respectively). However, in predicting histologic chorioamnionitis, there were no significant differences in AUCs among the three tests (AF MMP-9: 0.78 [95% CI, 0.68-0.85]; AF IL-6: 0.76 [95% CI, 0.66-0.84]; serum CRP: 0.76 [95% CI, 0.66-0.84]). In a sub-analysis of 71 women without intra-amniotic infection, histologic chorioamnionitis was associated with an elevated serum CRP level (P < 0.05), but not with the level of AF IL-6 or MMP-9 (P = 0.232 and P = 0.402, respectively). CONCLUSIONS: The AF MMP-9 has a better overall diagnostic performance than the AF IL-6 and maternal serum CRP in predicting intra-amniotic infection. However, the serum CRP level obtained up to 72 h before delivery appears to be an important marker for early identification of histologic chorioamnionitis in women without intra-amniotic infection.

Influence of killer cell immunoglobulin-like receptor genotypes on acute graft-vs-host disease after unrelated hematopoietic stem cell transplantation in Koreans.

Interactions between killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen class I ligands influence the development of the natural killer cell repertoire and the responses to infection, cancer, and allogeneic tissue. In this study, the association of KIR genes with acute graft-vs-host disease (GVHD) was investigated in 44 pairs of leukemia patients and their unrelated donors for hematopoietic stem cell transplantation (HSCT). Donors with more than 12 KIR genes showed significantly decreased frequencies of severe acute GVHD compared with donors with less than 11 KIR genes (P < 0.05). The distribution of KIR genotypes was not different between severe and mild acute GVHD in patients and donors, respectively. These results suggest that the number of KIR genes in donors could influence the occurrence of acute GVHD after unrelated HSCT.

Effects of ADP on different inhibitory properties of brain glutamate dehydrogenase isoproteins by perphenazine.

Incubation of glutamate dehydrogenase isoproteins (GDH I and GDH II) from bovine brains with perphenazine resulted in a time-dependent loss of enzyme activity. 2-Oxoglutarate and NADH, separately or together, gave partial but not complete protection against the inhibition. Although there were no detectable differences between GDH I and GDH II in inhibition by perphenazine in the absence of ADP, the sensitivities to the inhibition by the drug were significantly distinct for the two isoproteins in the presence of ADP. Low concentrations of ADP (0.05-0.20 mM) did not interfere with the inhibition of GDH I and GDH II by perphenazine. However, in the presence of high concentrations of ADP (0.5-1.0 mM), inhibitory effects of perphenazine on GDH isoproteins were significantly diminished as determined by enzyme kinetics and quantitative affinity chromatography on perphenazine-Sepharose. GDH I was more sensitively reacted with ADP than GDH II on the inhibition by perphenazine. Since physiological ADP levels can vary from 0.05 to > 1.0 mM depending on the rate of oxidative phosphorylation, our results suggest a possibility that two types of GDHs are differently regulated by the antipsychotic actions of perphenazine depending on the physiological concentrations of ADP. GTP and L-leucine, other well-known allosteric regulators, did not affect the inhibitory actions of perphenazine on bovine brain GDH isoproteins.

Proteolytic processing of oligopeptides containing the target sequences by the recombinant tobacco vein mottling virus NIa proteinase.

Tobacco vein mottling virus (TVMV) belongs to the potyviridae that consists of about 200 plant viruses. Potyviruses have RNA genomes of approximately 10,000 bases from which a single polyprotein is expressed from each virus upon infection. The NIa proteinase is known to process the polyprotein at seven distinct junctions between proteins. Kinetic constants were determined for the reactions of the recombinant TVMV NIa protease (27 kDa) with synthetic oligopeptides containing the sequences for the cleavage sites. For optimum activity, the substrate needs to have six amino acids (P6-P1) in the amino region and four (P1'-P4') in the carboxy region, including four conserved amino acids (V-R-F-Q) in P4-P1 positions. Mutation of any of four conserved amino acids to Gly made the substrate inert to the enzyme. Among the substrates, the oligopeptides containing the sequences for junctions, P3-6K1, NIa (VPg-Pro), and NIa-NIb were not processed by the NIa protease. Those junctions have Glu at P3, Glu at P1, and Thr at P2. The implications of high substrate specificity and size dependence in polyprotein processing and viral replication are discussed.

Fluorometric assay of turnip mosaic virus NIa protease.

Turnip mosaic virus (TuMV) NIa protease cleaves the viral polyprotein at seven distinct junctions out of nine. The amino acid sequences of the seven cleavage sites have three conserved amino acids, V, H, Q in positions P4, P2, P1, respectively. Small molecules as well as conjugated peptides were tested for proteolytic activity of the enzyme. None of small molecules tested, such as methylumbelliferyl-p-guanidinobenzoate, p-nitrophenyl-p'-guanidinobenzoate, p-nitrophenyl acetate, and methylumbelliferyl-N-acetylglutamate, were hydrolyzed. Ac-V-Y-H-Q-Mca was also not hydrolyzed. Intramolecularly quenched fluorogenic substrates Dns-P-V-Y-H-Q-A-W-NH(2) and Dns-P-V-Y-H-Q-W-NH(2) emitted fluorescence after addition of TuMV NIa protease. The proteolysis rate of Dns-P-V-Y-H-Q-A-W-NH(2) was comparable to that of the tetradecapeptide with an optimum sequence, but Dns-P-V-Y-H-Q-W-NH(2) was hydrolyzed at a slower rate, which was confirmed independently by HPLC analysis. These results suggest that intramolecularly quenched fluorogenic substrates can be used for the continuous assay of TuMV NIa protease.

Photoaffinity labeling of brain glutamate dehydrogenase isoproteins with an azido-ADP.

The ADP binding site within two types of bovine brain glutamate dehydrogenase isoproteins (GDH I and GDH II) was identified using photoaffinity labeling with [alpha-32P]8-azidoadenosine 5'-diphosphate (8N3ADP). 8N3ADP, without photolysis, mimicked the activatory properties of ADP on GDH I and GDH II activities, although maximal activity with 8N3ADP was about 75% of maximal ADP-stimulated activity. Saturation of photoinsertion with [alpha-32P]8N3ADP occurred at around 40 approximately 50 microM photoprobe with apparent Kd values near 25 and 40 microM for GDH I and GDH II, respectively. Photoinsertion of [alpha-32P]8N3ADP was decreased best by ADP in comparison with other nucleotides. With the combination of immobilized aluminum affinity chromatography and reversed-phase high performance liquid chromatography, photolabel-containing peptides generated by tryptic digestion were isolated. This identified a portion of the adenine ring binding domain of GDH isoproteins as in the region containing the sequence, EMSWIADTYASTIGHYDIN. Photolabeling of the peptide was prevented over 90% by the presence of 1 mM ADP during photolysis, while other nucleotides could not reduce the amount of photoinsertion as effectively as ADP. These results demonstrate selectivity of the photoprobe for the ADP binding site and suggest that the photolabeled peptide with the residues Glu179-Asn197 is within the ADP binding domain of the brain GDH isoproteins.

Regulation of integrin alpha 5 beta 1 affinity during myogenic differentiation.

The antigen recognized by U1 alpha, a monoclonal antibody to the alpha chain of a chicken integrin fibronectin receptor, was identified as alpha 5. It identifies the same polypeptide as antisera raised to a sequence from the alpha 5 cytoplasmic domain. The U1 alpha antibody has the unusual functional property for alpha chain antibodies of enhancing the binding of alpha 5 beta 1 for its ligand fibronectin. U1 alpha was used to examine the function of alpha 5 beta 1 during myogenic differentiation. As myogenic cells differentiated from replicating myoblasts to bipolar myocytes there was a decrease in their adhesion to the substrate caused by inactivation of alpha 5 beta 1, which could be reversed by treatment of the cells with U1 alpha. The U1 alpha induced increased adhesion to fibronectin but did not inhibit the differentiation process as measured by formation of myotubes. However, U1 alpha did interfere with both cell migration and morphogenesis of myotubes. The resulting myotubes were smaller, more branched, and showed less regular alignment of nuclei. The results suggest that the ability of the cell to regulate alpha 5 beta 1 affinity is critical to myogenic morphogenesis.