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61.
Fahd Al-Mulla Mahera Abdulrahman Govindarajulu Varadharaj Nadeem Akhter Jehoram T Anim 《The journal of histochemistry and cytochemistry》2005,53(5):621-629
Breast cancer is a major cause of cancer-related mortality in women. There are major discrepancies concerning the usefulness of various antibodies in detecting breast cancer susceptibility gene 1 (BRCA1) protein and its subcellular localization. The aim of the present study was to determine the specificity and sensitivity of immunohistochemistry (IHC) as a screening method for demonstrating BRCA1 expression. BRCA1 gene expression in archival paraffin-embedded breast cancer tissues was studied simultaneously at the protein and mRNA levels, and the two findings were compared. Forty-eight archival paraffin-embedded breast cancer tissues were studied for BRCA1 gene expression at protein level by IHC using four different antibodies against different BRCA1 epitopes and at mRNA level using real-time RT-PCR. BRCA1 mRNA expression was reduced or absent in 79% of the samples, and this finding correlated significantly with loss of BRCA1 protein expression in 83% of breast cancer tissues using one BRCA1 antibody studied (AB-1, against N-terminus epitope). The specificity of this antibody was 91.3%, and its sensitivity was 66.6%. There was no significant correlation between BRCA1 mRNA and protein expression as demonstrated by the remaining three antibodies. Antibody 8F7 had the highest sensitivity of 100%, but its specificity was 30.4% if mRNA levels were considered as the reference standard. 相似文献
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Danesh J Kaptoge S Mann AG Sarwar N Wood A Angleman SB Wensley F Higgins JP Lennon L Eiriksdottir G Rumley A Whincup PH Lowe GD Gudnason V 《PLoS medicine》2008,5(4):e78
Background
The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context.Methods and Findings
Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28–0.53, over 4 y, and 0.35, 95% CI 0.23–0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29–1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45–3.15) with long-term average (“usual”) IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42–1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45–4.56] per 2 SD increase in usual [long-term average] IL-6 levels).Conclusions
Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6–mediated pathways to CHD. 相似文献63.
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Sumbal Nosheen Nadeem Irfan Bukhari Kashaf Junaid Naeem Anwar Fahad Ahmad Sonia Younas Hasan Ejaz 《Saudi Journal of Biological Sciences》2021,28(10):5875
The evolution of NDM genes (blaNDM) in E. coli is accounted for expansive multidrug resistance (MDR), causing severe infections and morbidities in the pediatric population. This study aimed to analyze the phylogeny and mutations in NDM variants of E. coli recovered from the pediatric population. Carbapenem-resistant clinical strains of E. coli were identified using microbiological phenotypic techniques. PCR technique used to amplify the blaNDM genes, identified on agarose gel, and analyzed by DNA sequencing. The amino acid substitutions were examined for mutations after aligning with wild types. Mutational and phylogenetic analysis was performed using Lasergene, NCBI blastn, Clustal Omega, and MEGA software, whereas PHYRE2 software was used for the protein structure predictions. PCR amplification of the blaNDM genes detected 113 clinical strains of E. coli with the contribution of blaNDM-1 (46%), blaNDM-4 (3.5%), and blaNDM-5 (50%) variants. DNA sequencing of blaNDM variants showed homology to the previously described blaNDM-1, blaNDM-4, and blaNDM-5 genes available at GenBank and NCBI database. In addition, the mutational analysis revealed in frame substitutions of Pro60Ala and Pro59Ala in blaNDM-4 and blaNDM-5, respectively. The blaNDM-1 was ortholog with related sequences of E. coli available at GenBank. The phylogenetic analysis indicated that the NDM gene variants resemble other microbes reported globally with some new mutational sites. 相似文献
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The plasma parameter studies of the Nd:YAG (neodymium-doped yttrium aluminum garnet, Nd:Y3Al15O12) crystal by using the fundamental (1064 nm) and second (532 nm) harmonics of Nd:YAG laser are reported. The electron temperature (T e ) and electron number density (N e) were determined using the Boltzmann plot method and the Stark-broadened line profile, respectively. An increase in the plasma parameters have been observed with an increase in the laser irradiance for both laser modes. The electron temperatures were calculated in the range of 0.53–0.66 eV for 1064 nm and 0.47–0.60 eV for 532 nm, and the electron number densities were determined in the range of 7.43 × 1015–3.27 × 1016 cm?3 for 1064 nm and 1.35 × 1016–3.97 × 1016 cm?3 for 532 nm in the studied irradiance range of 1.19–12.5 GW/cm2. However, the spatial evolution of the plasma parameters investigated up to 2.75 mm away from the target surface at a fixed laser irradiance of 6.51 GW/cm2 showed a decreasing trend. In addition, the estimated values of the inverse bremsstrahlung (IB) absorption coefficients at both laser wavelengths showed that the IB process is dominant for the 1064-nm laser. 相似文献
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Boron is an essential plant micronutrient, but it is phytotoxic if present in excessive amounts in soil for certain plants
such as Artemisia annua L. that contains artemisinin (an important antimalarial drug) in its areal parts. Artemisinin is a sesquiterpene lactone
with an endoperoxide bridge. It is quite expensive compound because the only commercial source available is A. annua and the compound present in the plant is in very low concentration. Since A. annua is a major source of the antimalarial drug and B stress is a deadly threat to its cultivation, the present research was conducted
to determine whether the exogenous application of methyl jasmonate (MeJA) could combat the ill effects of excessive B present
in the soil. According to the results obtained, the B toxicity induced oxidative stress and reduced the stem height as well
as fresh and dry masses of the plant remarkably. The excessive amounts of soil B also lowered the net photosynthetic rate,
stomatal conductance, internal CO2 concentration and total chlorophyll content in the leaves. In contrast, the foliar application of MeJA enhanced the growth
and photosynthetic efficiency both in the stressed and non-stressed plants. The excessive B levels also increased the activities
of antioxidant enzymes, such as catalase, peroxidase and superoxide dismutase. Endogenous H2O2 and O2− levels were also high in the stressed plants. However, the MeJA application to the stressed plants reduced the amount of
lipid peroxidation and stimulated the synthesis of antioxidant enzymes, enhancing the content and yield of artemisinin as
well. Thus, it was concluded that MeJA might be utilized in mitigating the B toxicity and improving the content and yield
of artemisinin in A. annua plant. 相似文献
70.
Arizmendi NG Abel M Mihara K Davidson C Polley D Nadeem A El Mays T Gilmore BF Walker B Gordon JR Hollenberg MD Vliagoftis H 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(5):3164-3172
We have shown that proteinase-activated receptor-2 (PAR(2)) activation in the airways leads to allergic sensitization to concomitantly inhaled Ags, thus implicating PAR(2) in the pathogenesis of asthma. Many aeroallergens with proteinase activity activate PAR(2). To study the role of PAR(2) in allergic sensitization to aeroallergens, we developed a murine model of mucosal sensitization to cockroach proteins. We hypothesized that PAR(2) activation in the airways by natural allergens with serine proteinase activity plays an important role in allergic sensitization. Cockroach extract (CE) was administered to BALB/c mice intranasally on five consecutive days (sensitization phase) and a week later for four more days (challenge phase). Airway hyperresponsiveness (AHR) and allergic airway inflammation were assessed after the last challenge. To study the role of PAR(2), mice were exposed intranasally to a receptor-blocking anti-PAR(2) Ab before each administration of CE during the sensitization phase. Mucosal exposure to CE induced eosinophilic airway inflammation, AHR, and cockroach-specific IgG1. Heat-inactivated or soybean trypsin inhibitor-treated CE failed to induce these effects, indicating that proteinase activity plays an important role. The use of an anti-PAR(2) blocking Ab during the sensitization phase completely inhibited airway inflammation and also decreased AHR and the production of cockroach-specific IgG1. PAR(2) activation by CE acts as an adjuvant for allergic sensitization even in the absence of functional TLR4. We conclude that CE induces PAR(2)-dependent allergic airway sensitization in a mouse model of allergic airway inflammation. PAR(2) activation may be a general mechanism used by aeroallergens to induce allergic sensitization. 相似文献