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101.
Szema AM Hamidi SA Lyubsky S Dickman KG Mathew S Abdel-Razek T Chen JJ Waschek JA Said SI 《American journal of physiology. Lung cellular and molecular physiology》2006,291(5):L880-L886
The mechanisms leading to asthma, and those guarding against it, are yet to be fully defined. The neuropeptide VIP is a cotransmitter, together with nitric oxide (NO), of airway relaxation, and a modulator of immune and inflammatory responses. NO-storing molecules in the lung were recently shown to modulate airway reactivity and were proposed to have a protective role against the disease. We report here that mice with targeted deletion of the VIP gene spontaneously exhibit airway hyperresponsiveness to the cholinergic agonist methacholine as well as peribronchiolar and perivascular cellular infiltrates and increased levels of inflammatory cytokines in bronchoalveolar lavage fluid. Immunologic sensitization and challenge with ovalbumin generally enhanced the airway hyperresponsiveness and airway inflammation in all mice. Intraperitoneal administration of VIP over a 2-wk period in knockout mice virtually eliminated the airway hyperresponsiveness and reduced the airway inflammation in previously sensitized and challenged mice. The findings suggest that 1) VIP may be an important component of endogenous anti-asthma mechanisms, 2) deficiency of the VIP gene may predispose to asthma pathogenesis, and 3) treatment with VIP or a suitable agonist may offer potentially effective replacement therapy for this disease. 相似文献
102.
Niiranen K Keinänen TA Pirinen E Heikkinen S Tusa M Fatrai S Suppola S Pietilä M Uimari A Laakso M Alhonen L Jänne J 《Journal of cellular and molecular medicine》2006,10(4):933-945
The N(1)-acetylation of spermidine or spermine by spermidine/spermine N(1)-acetyltransferase (SSAT) is the ratecontrolling enzymatic step in the polyamine catabolism. We have now generated SSAT knockout (SSAT-KO) mice, which confirmed our earlier results with SSATdeficient embryonic stem (ES) cells showing only slightly affected polyamine homeostasis, mainly manifested as an elevated molar ratio of spermidine to spermine in most tissues indicating the indispensability of SSAT for the spermidine backconversion.Contrary to SSAT deficient ES cells, polyamine pools in SSAT-KO mice remained almost unchanged in response to N(1),N(11)-diethylnorspermine (DENSPM) treatment compared to a significant reduction of the polyamine pools in the wild-type animals and ES cells. Furthermore, SSATKO mice were more sensitive to the toxicity exerted by DENSPM in comparison with wild-type mice. The latter finding indicates that inducible SSAT plays an essential role in vivo in DENSPM treatmentevoked polyamine depletion, but a controversial role in toxicity of DENSPM. Surprisingly, liver polyamine pools were depleted similarly in wild-type and SSAT-KO mice in response to carbon tetrachloride treatment. Further characterization of SSAT knockout mice revealed insulin resistance at old age which supported the role of polyamine catabolism in glucose metabolism detected earlier with our SSAT overexpressing mice displaying enhanced basal metabolic rate, high insulin sensitivity and improved glucose tolerance. Therefore SSAT knockout mice might serve as a novel mouse model for type 2 diabetes. 相似文献
103.
Martinmäki K Rusko H Kooistra L Kettunen J Saalasti S 《American journal of physiology. Heart and circulatory physiology》2006,290(2):H640-H647
Heart rate variability (HRV) has been widely used as a measure of vagal activation in physiological, psychological, and clinical examinations. We studied the within-subject quantitative relationship between HRV and vagal effects on the heart in different body postures during a gradually decreasing vagal blockade. Electrocardiogram and respiratory frequency were measured in subjects (8 endurance athletes and 10 participants of nonendurance sports) in supine, sitting, and standing postures before the blockade, under vagal blockade (atropine sulfate, 0.04 mg/kg), and four times during a 150-min recovery from the blockade. Fast Fourier transform was used to calculate low-frequency power (LFP, 0.04-0.15 Hz), high-frequency power (HFP, 0.15-0.40 Hz), and total power (TP, 0.04-0.40 Hz). A within-subject linear regression analysis of recovery time on each HRV index was conducted. Complete vagal blockade decreased all HRV significantly, particularly HFP (P < 0.001). A linear fit explained a large portion of the within-subject variance between recovery time and natural log-transformed (ln) HRV indexes in every posture, with coefficients of determination (R2) in the supine posture [means (SD)]: 98 (SD 2)% for mean R-R interval, 87 (SD 10)% for lnLFP, 87 (SD 13)% for lnHFP, and 91 (SD 10)% for lnTP. Neither body posture nor endurance-training background had an impact on R2 values. There was marked between-subject variation in the R2 values, slopes, and intercepts. In conclusion, all HRV, particularly HFP, is predominantly under vagal control. Within subjects, lnLFP, lnHFP, and lnTP increased linearly with the gradually decreasing vagal blockade in all postures. 相似文献
104.
A moderately halophilic, mesophilic, Gram-negative, motile, nonsporulating bacterium, designated strain IMPC, was isolated from a table-olive fermentation rich in aromatic compounds, after enrichment on p-coumaric acid under halophilic conditions. Strain IMPC was able to degrade p-coumaric acid. p-hydroxybenzaldehyde and p-hydroxybenzoic acid were detected as breakdown products from p-coumaric acid. Protocatechuic acid was identified as the final aromatic product of p-coumaric acid catabolism before ring fission. Strain IMPC transformed various cinnamic acids with substituent H, OH, CH(3) or OCH(3) in the para- and/or meta-position of the aromatic ring to the corresponding benzoic acids, indicating a specific selection. A beta-oxidation pathway was proposed for these transformations. Phylogenetic analysis of the 16S rRNA gene revealed that this isolate was a member of the genus Halomonas. Strain IMPC was closely related to Halomonas elongata ATCC 33173(T)and Halomonas eurihalina ATCC 49336(T). 相似文献
105.
We investigated the effect of untreated and biologically treated olive mill wastewater (OMW) spreading on the soil characteristics and the microbial communities. The water holding capacity, the salinity and the content of total organic carbon, humus, total nitrogen, phosphate and potassium increased when the spread amounts of the treated or untreated OMW increased. The OMW treated soil exhibited significantly higher respiration compared to the control soil. However, the C-CO2/C(tot) ratio decreased from 1.7 in the control soil to 0.5 in the soil amended with 100 m3 ha(-1) of untreated OMW. However, it slightly decreased to 1.15 in the soil amended with 400 m3 ha(-1) of treated OMW. The treated OMW increased the total mesophylic number while the number of fungi and nitrifiers decreased. Actinomycetes and spore-forming bacteria were neither sensitive to treated nor to untreated OMW. The total coliforms increased with higher doses of treated and untreated OMW. A toxic effect of the untreated OMW appeared from 100 m3 ha(-1). This toxicity was more significant with 200 m3 ha(-1), where microflora of total mesophilic, yeasts and moulds, actinomycetes, and nitrifiers were seriously inhibited except for total coliforms and spore-forming bacteria. 相似文献
106.
An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling 总被引:5,自引:3,他引:2 下载免费PDF全文
Pirone DM Liu WF Ruiz SA Gao L Raghavan S Lemmon CA Romer LH Chen CS 《The Journal of cell biology》2006,174(2):277-288
Focal adhesion kinase (FAK) transduces cell adhesion to the extracellular matrix into proliferative signals. We show that FAK overexpression induced proliferation in endothelial cells, which are normally growth arrested by limited adhesion. Interestingly, displacement of FAK from adhesions by using a FAK−/− cell line or by expressing the C-terminal fragment FRNK also caused an escape of adhesion-regulated growth arrest, suggesting dual positive and negative roles for FAK in growth regulation. Expressing kinase-dead FAK-Y397F in FAK−/− cells prevented uncontrolled growth, demonstrating the antiproliferative function of inactive FAK. Unlike FAK overexpression–induced growth, loss of growth control in FAK−/− or FRNK-expressing cells increased RhoA activity, cytoskeletal tension, and focal adhesion formation. ROCK inhibition rescued adhesion-dependent growth control in these cells, and expression of constitutively active RhoA or ROCK dysregulated growth. These findings demonstrate the ability of FAK to suppress and promote growth, and underscore the importance of multiple mechanisms, even from one molecule, to control cell proliferation. 相似文献
107.
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109.
In the present study we investigated the respiratory burst (RB) activity of Atlantic cod (Gadus morhua L.) blood phagocytes and we evaluated how the RB activity of cod blood cells differ from that of trout. The RB activities were measured directly from highly diluted whole blood as luminol-amplified chemiluminescence (CL) under various conditions. Studies regarding the blood dilutions for cod whole blood chemiluminescence measurements (WBCL) revealed that at a final blood dilution of 1.5 microl ml(-1) or less the CL response was strictly proportional to the number of phagocytes. This range of blood dilution did not markedly differ from that of trout. However, the opsonisation capacity of cod plasma was markedly poorer. The RB activity of phagocytes was most active at 15 degrees C when heterologous cod serum was used as a source of opsonin, whereas at final blood dilution of 8.0 microl ml(-1) (when homologous cod plasma was at a higher concentration) the highest RB activity was observed at 10 degrees C. Aeromonas salmonicida strain MT004 (As MT004) induced higher RB activity than the two known pathogens for cod, atypical A. salmonicida and Vibrio anguillarum. Cod blood phagocytes were more responsive to plastic surfaces and the adhesion response of phagocytes was partly inhibited but did not totally vanish even at a final gelatin concentration of 0.4%. Moreover, cod serum enhanced the adherence of phagocytes and cod blood phagocytes also showed slow spontaneous degranulation. Finally, within the tested anticoagulants (heparin, Na-citrate, EDTA) heparin treated blood phagocytes generated the highest RB activity. 相似文献
110.
Sulieman Ibraheem Shelash Al-Hawary Anas Yahya Ali Yasser Fakri Mustafa Ria Margiana Shamsutdinova Maksuda Ilyasovna Montather F. Ramadan Sami G. Almalki Marim Alwave Safa Alkhayyat Ali Alsalamy 《Biotechnology progress》2023,39(6):e3383
Altered expression of multiple miRNAs was found to be extensively involved in the pathogenesis of different neurological disorders including Alzheimer's disease, Parkinson's disease, stroke, epilepsy, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. One of the biggest concerns within gene-based therapy is the delivery of the therapeutic microRNAs to the intended place, which is obligated to surpass the biological barriers without undergoing degradation in the bloodstream or renal excretion. Hence, the delivery of modified and unmodified miRNA molecules using excellent vehicles is required. In this light, mesenchymal stem cells (MSCs) have attracted increasing attention. The MSCs can be genetically modified to express or overexpress a particular microRNA aimed with promote neurogenesis and neuroprotection. The current review has focused on the therapeutic capabilities of microRNAs-overexpressing MSCs to ameliorate functional deficits in neurological conditions. 相似文献