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Increased Fraction (increased + fraction)
Selected AbstractsThe mediterranean fever gene modifies the progression of disability in non-Ashkenazi Jewish multiple sclerosis patientsJOURNAL OF NEUROCHEMISTRY, Issue 2002Y. Shinar MS is an autoimmune, CNS demyelinating disease manifested in most patients with progressive disability. The progression rate varies between patients and may depend on modifier, immune related genes. The Mediterranean fever gene, expressed in peripheral blood leukocytes, is responsible for familial Mediterranean fever (FMF), a recessive, periodic autoinflammatory disease prevalent in Semitic populations, and less penetrant in Ashkenazi Jews. We related common, FMF associated MEFV mutations to the progression of disability in Jewish, relapsing remitting (RR) MS patients. The mutations 148Q, 694V, 695R and 726A were identified by enzymatic restriction of PCR-amplified MEFV DNA. The progression to statuses 3 and 6 of the expanded disability status scale (EDSS) was analyzed on survival plots. 35% of 48 non-Ashkenazi patients had one MEFV mutation. Compared to non-carriers (n = 31) the heterozygous cohort (n = 17) represented with an increased fraction reaching both EDSS statuses (p < 0.05), and with a shorter median time to reach both EDSS =,3 (2 years in carriers vs. 10 years in non-carriers, p < 0.01) and EDSS =,6 (6 vs. 23 years, respectively, p < 0.005). 17% of 71 Ashkenazi patients had one MEFV mutation. There was no significant difference in the fraction of disabled or in the progression of disability between Ashkenazi carrier patients and non-carriers. The susceptibility of the non-Ashkenazi group attributed, in part, to the detrimental non-Ashkenazi 694V mutation. The results suggest phenotypic expression of one mutated MEFV gene in non-ashkenazi patients, pertinent to the pathogenesis of disability. Acknowledgements:, Granted by the Israeli Ministry of Science (#6279). [source] Decreased oxygen saturation as a result of haemoglobin TitusvilleTHE CLINICAL RESPIRATORY JOURNAL, Issue 4 2008H. Avellan-Hietanen Abstract Introduction:, Our patient was admitted to the hospital due to shortness of breath. Although partial pressure of oxygen in arterial blood was normal, oxygen saturation measured with pulse oximetry (SpO2) was markedly decreased. SpO2 and oxygen saturation of arterial blood (SaO2) stayed low during monitoring even with an increased fraction of oxygen in inspired air. Methods:, Report of a case. Results:, After extensive investigations, a rare haemoglobin variant, haemoglobin Titusville, with decreased oxygen binding capacity was discovered. This is the first haemoglobin Titusville case reported in Scandinavian countries. Please cite this paper as: Avellan-Hietanen H, Aittomaki J, Ekroos H, Aittomäki K, Turpeinen U, Kalkkinen N and Sovijärvi A. Decreased oxygen saturation as a result of haemoglobin Titusville. The Clinical Respiratory Journal 2008; 2: 242,244. [source] Overexpression of EIF3S3 promotes cancer cell growthTHE PROSTATE, Issue 11 2006Kimmo J. Savinainen Abstract BACKGROUND Amplification and overexpression of EIF3S3 gene has been demonstrated in breast and prostate cancer. Here, our goal was to study the effect of EIF3S3 on cell growth. METHODS The effect of EIF3S3 on growth of NIH 3T3 murine fibroblasts as well as breast (SK-Br-3 and ZR-75-1) and prostate (PC-3 and LNCaP) cancer cell lines was examined by using transfection with inducible pTet-Off system and siRNAs. RESULTS NIH 3T3 cells with overexpression of EIF3S3 grew significantly faster than cells transfected with empty vector and survived longer when grown in soft agar. The EIF3S3 overexpression was associated with increased fraction of cells in S-phase and with phosphorylation of retinoblastoma (Rb) protein. siRNA treatment inhibited significantly (P,=,0.0022) the growth of all breast and prostate cancer cell lines studied. CONCLUSIONS The results suggest that EIF3S3 regulates cell growth and viability, and that overexpression of the gene may provide growth advantage to the cancer cells. Prostate © 2006 Wiley-Liss, Inc. [source] Evidence of dysfunctional ,2 -adrenoceptor signal system in pre-eclampsiaBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 1 2000B. Aune Senior Registrar Objectives To determine how ,2 -adrenoceptor binding and function differ between healthy women and those with pre-eclampsia. Design Case-control study. Setting Faculty of Medicine, University of Tromsø, Norway. Participants Two groups of pregnant women: eight cases with pre-eclampsia, matched with eight healthy controls. Methods Venous blood was drawn from women in both groups after an overnight rest. The two groups were matched for gestational age which was (mean (SD)) 36.4 (3.8) and 36.5 (4.4) weeks for the pre-eclamptic and control groups, respectively. Six weeks after delivery a second blood sample was obtained. The binding and function of ,2 -adrenoceptors were determined in isolated human mononu-clear leukocytes. The levels of adrenaline and noradrenaline were determined in plasma from venous blood. Results An elevated density of functional ,2 -adrenoceptors was observed in normal pregnancy [mean (SD) 390 (90) vs 270 (60) sites/cell postpartum], due to an increased fraction of receptors in high affinity state, with unaltered total receptor density. The number of functional ,2 -adrenoceptors was reduced in pre-eclampsia [mean (SD) 80 (40) vs 240 (30) sites/cell postpartum], due to a reduction in the total receptor number with an unaltered fraction of high affinity receptors. In pregnancy, both unstimulated and isoprenaline-stimulated cAMP levels were reduced in the women with pre-eclampsia (0.5 (0.2) and 1.7 (0.9) pmol/106 cells, respectively) compared with the normal pregnant controls (mean (SD) 1.2 (0.3) and 4.7 (1.8) pmol/106 cells, respectively). Plasma catecholamine levels were not elevated in the women with pre-eclampsia. Conclusions The increased number of functional ,2 -adrenoceptors may contribute to the vasodilatation seen in normal pregnancy, while the reduced overall number of receptors may be one of several factors that account for increased peripheral vascular resistance in pre-eclampsia. [source] In vitro and in vivo antineoplastic activity of a novel bromopyrrole and its potential mechanism of actionBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2010Sheng Xiong Background and purpose:, Many bromopyrrole compounds have been reported to have in vitro antineoplastic activity. In a previous study, we isolated N-(4, 5-dibromo-pyrrole-2-carbonyl)-L-amino isovaleric acid methyl ester (B6) from marine sponges. Here, we investigated the in vitro and in vivo antineoplastic activity of B6 and its potential mechanism. Experimental approach:, The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to determine the in vitro antineoplastic activity of B6. Flow cytometry, western blot analysis and morphological observations were used to investigate its mechanism of action. A mouse xenograft model was used to determine its in vivo activity. Key results:, B6 inhibited the proliferation of various human cancer cells in vitro, with highest activity on LOVO and HeLa cells. B6 also exhibited significant growth inhibitory effects in vivo in a xenograft mouse model. Acute toxicity analysis suggested that B6 has low toxicity. B6-treated cells arrested in the G1 phase of the cell cycle and had an increased fraction of sub-G1 cells. In addition, the population of Annexin V-positive/propidium iodide-negative cells increased, indicating the induction of early apoptosis. Indeed, B6-treated cells exhibited morphologies typical of cells undergoing apoptosis. Western blotting showed cleaved forms of caspase-9 and caspase-3 in cells exposed to B6. Moreover, B6-promoted Ca2+ release and apoptosis was associated with elevated intracellular Ca2+concentration. Conclusions and implications:, B6 has significant antineoplastic activity in vitro as well as in vivo. It inhibits tumour cell proliferation by arresting the cell cycle and inducing apoptosis. With its low toxicity, B6 represents a promising antineoplastic, primary compound. [source] Diffusion and NOE NMR Studies on Multicationic DAB-Organoruthenium Dendrimers: Size-Dependent Noncovalent Self-Assembly to Megamers and Ion Pairing,CHEMISTRY - A EUROPEAN JOURNAL, Issue 21 2009Stefania Pettirossi Dr. Abstract Supra-mega ion pairing: Multicationic organoruthenium dendrimers show a notable tendency to self-aggregate when the concentration is increased, leading to megamers. This tendency increases with the generation. The self-aggregation of dendrimers to megamers is coupled with a decrease in the extent of ion pairing, as illustrated. New multicationic organoruthenium dendrimers (RuPF6 -Dabn, n=2, 4, 8, 16) have been synthesized by coupling of [Ru(,6 - p -cymene)(,3 -dpk-OCH2CH2OH)]X (1PF6, dpk=2,2,-dipyridyl ketone, X=PF6) with 1,4-diaminobutane (DAB) and polypropylenimine dendrimer DAB- dendr -(NH2)n {n=4, 8, 16} mediated by 1,1,-carbonyldiimidazole (CDI). The intermediate in the synthesis, [Ru(,6 - p -cymene)(,3 -dpk-OCH2CH2OC(O)Im]X (2PF6, Im=imidazole, X=PF6) has been isolated and characterized by single-crystal XRD. The intra- and supramolecular structures in a solution of RuPF6 -Dabn dendrimer have been investigated by multidimensional and multinuclear NMR techniques. Diffusion NMR experiments on dilute solutions indicated that the linear distance between two metal centers (14.9,22.1,Å depending on the dendrimer generation) is much greater than the diameter of 1PF6 (9.9,Å). 19F,1H-HOESY NMR experiments (HOESY= heteronuclear Overhauser effect spectroscopy) showed that the counterion is positioned on the surface of the dendrimers and assumes the same relative anion,cation orientation as in 2PF6. Diffusion NMR experiments on RuPF6 -Dabn dendrimers in CD2Cl2 at different concentrations revealed a process of supramolecular assembly of dendrimers to megamers that is strongly favored for the highest generations. Megamer formation is coupled with an increased fraction of free ions (,) and a consequent reduction in ion-paired ruthenium centers. Graphs of , versus CRu (the concentration of ruthenium centers) showed a minimum for RuPF6 -Dab4, RuPF6 -Dab8, and RuPF6 -Dab16 at a position coinciding with the significant presence of supramolecular dendritic dimers. The tendency to ion pairing decreases as the dendrimer generation increases. [source] | ||||||||||