To determine whether palmitic acid methyl ester (PAME) or methyl palmitate is the retina-derived relaxing factor (RRF).
A superfusion bioassay cascade technique was used with rat isolated retina as ...donor tissue and rat aortic ring as detector tissue. The superfusate was analyzed with gas chromatography/mass spectrometry (GC/MS). The biochemical and pharmacologic characteristics of RRF and PAME were compared.
The authors demonstrated that the retina on superfusion with Krebs solution spontaneously released RRF (indicated by aortic ring relaxation) and PAME (measured by GC/MS). The release of RRF and PAME was calcium dependent because the release was abolished when the retinas were superfused with calcium-free Krebs solution. Furthermore, aortic relaxations induced by RRF and PAME were not affected after heating their solutions at 70 degrees C for 1 hour, suggesting that both are heat stable. Exogenous PAME concentration dependently induced aortic relaxation with EC50 of 0.82+/-0.75 pM. The aortic relaxations induced by RRF and exogenous PAME were inhibited by 4-aminopyridine (2 mM) and tetraethylammonium (TEA, 10 mM) but were not affected by TEA at 1 mM or 3 mM, glibenclamide (3 microM), or iberiotoxin (100 nM). The vasodilator activity of Krebs solution containing RRF or exogenous PAME was greatly attenuated after hexane extraction.
RRF and PAME share similar biochemical properties and react similarly to all pharmacologic inhibitors examined. Both act primarily on the voltage-dependent K+ (Kv) channel of aortic smooth muscle cells, causing aortic relaxation. These results suggest that PAME is the hydrophobic RRF.
The research aim was to examine the effects of a Critique-Driven Inquiry (CDI) intervention on primary and secondary school students’ critical thinking and scientific inquiry competency. Twenty-five ...4th grade Taiwanese students from a typical primary school were selected to participate in experimental group 1 (EG1), while 28 7th grade students from a typical secondary school were randomly selected to participate in experimental group 2 (EG2). For each group, a 2-semester CDI intervention was implemented. In addition, another 28 4th graders and 30 7th graders from the same two schools were selected to participate in, respectively, control group 1 (CG1) or control group 2 (CG2). Analyses of covariance, repeated measures analysis of variance, and content theme analyses were conducted to analyze the quantitative and qualitative data. Research results indicated that EG1 and EG2 students significantly outperformed their comparison counterparts in critical thinking and scientific inquiry competency both during and following the CDI intervention. The empirical evidence provides insight into the mechanisms of promoting primary and secondary school students’ critical thinking and scientific inquiry competency.
Using gamma-ray irradiation, a pair of virulent (RP-9) and attenuated (RP-2ms) variants of Japanese encephalitis virus (JEV) were generated from a Taiwanese isolate, NT109. The two variants differed ...in plaque morphology, virus adsorption, and growth properties in BHK-21 cells: (i) RP-2ms produced smaller plaques than RP-9; (ii) RP-2ms adsorbed less efficiently to host cells but yielded a higher virus titer (burst size); and (iii) RP-2ms virions were mostly accumulated intracellularly, whereas RP-9 was released extracellularly. In addition, in an in vitro binding assay, the envelope (E) protein of RP-9, but not that of RP-2ms, bound specifically to a cellular protein of 57-kDa derived from BHK-21 cells. When injected into mice intracerebrally, RP-2ms was much less virulent than RP-9, with 50% lethal doses of > 10(7) and 0.4 plaque forming units, respectively. Moreover, when inoculated intraperitoneally, their organ tropism differed in that the main target organ for RP-2ms was liver, whereas that for RP-9 was brain. These results suggest that RP-2ms was less neurovirulent and less neuroinvasive from peripheral routes. Molecular analysis of the virus structural proteins detected only two differences between RP-9 and RP-2ms: one in E protein, Glu-138 in RP-9 and Lys-138 in RP-2ms, and the other in prM, Tyr-43 in RP-9 and His-43 in RP-2ms. Since the N-terminal 92 amino acids of prM are cleaved and not present in mature JEV virions, the single-amino-acid change of the E protein at position 138 may account for the difference between the mutants in the in vitro binding assay. Such mutation in E protein, or perhaps in conjunction with the prM mutation, may be responsible, in part, for the phenotypic differences observed in vitro and in vivo between the two mutants.
We examined gene expression of hepatocyte growth factor (HGF) and HGF receptor (HGFR), or product of proto-oncogene c-met (c-met), in smokers and nonsmokers with adenocarcinoma (ADC) by suppression ...subtractive hybridization and microarray techniques. Expression of HGF and c-met was confirmed by RT-PCR. HGF content in the respective tumor mass and nontumor lung tissue was measured by ELISA. HGF in pathologic samples was localized by immunohistochemistry and in situ hybridization. Our results indicate that overexpression of HGFR was frequently detected in ADC cells, whereas overexpression of HGF was detected in alveolar type II (ATII) cells. Overexpression of HGF was correlated with cigarette smoking and tumor stages. In vitro, HGF expression was evaluated in isolated murine ATII cells and in 12 ADC cell lines, and we found that nicotine activated HGF expression in ATII cells and lung cancer cells.
Sorafenib is an oral tyrosine kinase inhibitor that is indicated for advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine the clinical outcomes of HCC patients ...receiving sorafenib in real-life clinical setting in comparison with formal clinical trials.
Patients diagnosed with advanced HCC between 2007 and 2015 at single institute were retrospectively enrolled and evaluated for survival and tolerability following sorafenib treatment. Overall survival (OS) and duration of treatment (TTP) were examined by different stratifications including age, gender, etiology, liver functions, and severities.
A total of 67 advanced HCC patients were enrolled for analysis. Of the 67 eligible patients, 66 patients (99%) were diagnosed as Barcelona Clinic Liver Cancer stage C and 45 (67%) were Child-Pugh A. Chronic hepatitis B virus infection was the main etiology (67%), followed by hepatitis C virus infection (12%) and alcohol liver disease (8%). The median duration of treatment was 3.0 months (95% CI 2.6-3.4 months) and median OS was 8.0 months (95% CI 5.0-11.0 months). By multivariate analysis, female gender (HR =2.462, 95% CI 1.126-5.387,
=0.024), Child-Pugh C (HR =3.913, 95% CI 1.063-14.410,
=0.04), extrahepatic spread (HR =2.123, 95% CI 1.122-4.015,
=0.021), and combined other therapies (HR =0.410, 95% CI 0.117-0.949,
=0.037) were the independent predictors of OS.
OS of advanced HCC patients treated with sorafenib was longer than that reported in the Asia-Pacific trial study. Impaired hepatic functions are associated with the shorter survival in real-life setting.
A physical map of the mouse genome is an essential tool for both positional cloning and genomic sequencing in this key model system for biomedical research. Indeed, the construction of a mouse ...physical map with markers spaced at an average interval of 300 kb is one of the stated goals of the Human Genome Project. Here we report the results of a project at the Whitehead Institute/MIT Center for Genome Research to construct such a physical map of the mouse. We built the map by screening sequenced-tagged sites (STSs) against a large-insert yeast artificial chromosome (YAC) library and then integrating the STS-content information with a dense genetic map. The integrated map shows the location of 9,787 loci, providing landmarks with an average spacing of approximately 300 kb and affording YAC coverage of approximately 92% of the mouse genome. We also report the results of a project at the MRC UK Mouse Genome Centre targeted at chromosome X. The project produced a YAC-based map containing 619 loci (with 121 loci in common with the Whitehead map and 498 additional loci), providing especially dense coverage of this sex chromosome. The YAC-based physical map directly facilitates positional cloning of mouse mutations by providing ready access to most of the genome. More generally, use of this map in addition to a newly constructed radiation hybrid (RH) map provides a comprehensive framework for mouse genomic studies.
This paper presents a novel non-parametric methodology – rough set theory – for accident occurrence exploration. The rough set theory allows researchers to analyze accidents in multiple dimensions ...and to model accident occurrence as factor chains. Factor chains are composed of driver characteristics, trip characteristics, driver behavior and environment factors that imply typical accident occurrence. A real-world database (2003 Taiwan single auto-vehicle accidents) is used as an example to demonstrate the proposed approach. The results show that although most accident patterns are unique, some accident patterns are significant and worth noting. Student drivers who are young and less experienced exhibit a relatively high possibility of being involved in off-road accidents on roads with a speed limit between 51 and 79
km/h under normal driving circumstances. Notably, for bump-into-facility accidents, wet surface is a distinctive environmental factor.
Inflammatory processes have been implicated in the cascade of events that lead to nerve cell death. In the nervous system, a number of genes involved in inflammation pathways are regulated ...post-transcriptionally via the interaction of their mRNAs with specific RNA-binding Hu proteins, the vertebrate homologues of the Drosophila ELAV (for embryonic lethal abnormal vision). The gene encoding ELAVL4, a member of the Hu family of proteins, is located 2 Mb from the chromosome 1p linkage region peak for age-at-onset (AAO) of Parkinson disease (PD) (LOD = 3.41). Nine single-nucleotide polymorphisms (SNPs) in ELAVL4 were genotyped for 266 multiplex families (1,223 samples). Additional genotyping in 377 singleton families was performed for a subset of five SNPs (SNPs 1-5) that were not in linkage disequilibrium. SNP 2 (located in the first intron of ELAVL4) showed a strong significant association with AAO of PD (P = 0.006), and SNP 5 (a coding SNP in ELAVL4) showed a moderately significant association (P = 0.035). Haplotype analysis revealed that the A-C haplotype at SNPs 2 and 3 has the strongest significant association with AAO (P = 0.0001) among all combinations of two or three loci. The A-C haplotype remained significant for AAO after the inclusion of the C allele at SNP 5 to this haplotype (A-C-C haplotype, P = 0.00018). Although SNP 5 was found to associate with PD risk in the early-onset subset of PD families (at least one affected with AAO <40 years, 60 families), we believe that it is a by-product of its association with AAO. Taken together, these results suggest a potential role for ELAVL4 as a modifier gene for AAO of PD.
We conducted a randomized, open-label, controlled, multicenter study to compare sulbactam/cefoperazone with cefotaxime in terms of efficacy and safety for the treatment of hospitalized patients with ...moderate-to-severe bacterial infections. More than two-thirds of the pathogens recovered from these patients produced β-lactamase. Two hundred-seven (88.1%) of the 235 patients enrolled completed the study and were included in the efficacy and safety evaluations. One hundred-three patients received sulbactam/cefoperazone (2–4 g/d) administered in evenly divided doses every 12 hours by a 30-minute intravenous drip; 104 patients received cefotaxime (6–12 g/d) administered in evenly divided doses every 6 or 8 hours by a 30-minute intravenous drip. The overall efficacy rates (i.e., cure or markedly improved) were 95% for the sulbactam/cefoperazone group and 90% for the cefotaxime group (P = .186), whereas the bacterial eradication rates were 85% for the sulbactam/cefoperazone group and 81% for the cefotaxime group (P = .467). Both drug regimens were well tolerated. Sulbactam/cefoperazone is effective and safe for the treatment of moderate-tosevere bacterial infections caused mainly by β-lactamase-producing organisms.
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