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At least 847 records · Page 47Linked to original sources
PubMed2005

A novel (TG)n(GA)m repeat polymorphism 254 bp downstream of the mast cell chymase (CMA1) gene is associated with atopic asthma and total serum IgE levels.

The gene for mast cell chymase (CMA1) is an ideal candidate for investigating genetic predisposition to atopic asthma, as it is an important mediator of inflammation and remodeling in the asthmatic lung. Various studies have examined the association between -1903 G/A polymorphism and allergic phenotypes, but inconsistent results have been obtained. We investigated the association of this SNP and a novel (TG)(n)(GA)(m) repeat polymorphism (accession no. BV210164) 254 bp downstream of the gene with asthma and its associated traits in a case-control study in two independent cohorts recruited from the Indian population. A significant association was observed for the (TG)(n)(GA)(m) repeat with asthma (p<0.05) in both the cohorts. Although no association was observed for the -1903 G/A SNP with asthma, a significant association was observed between the genotypes and serum IgE levels (p=0.003 and 0.0004 for cohort A and B). When haplotypes were compared between patients and controls, the haplotype G_43 was found at higher frequency in controls (p=0.05). Also, on comparing major haplotypes (>5%) with respect to log total serum IgE levels, a significant difference was obtained (p=0.018 and p=0.046 for cohorts A and B). These results suggest that the CMA1 gene contributes to asthma susceptibility and may be involved in regulating IgE levels in atopic asthma.

Adult↗
PubMed2006

Dynamic particle image velocimetry flow analysis of the flow field immediately downstream of bileaflet mechanical mitral prostheses.

New dynamic particle image velocimetry (PIV) technology was applied to the study of the flow field associated with prosthetic heart valves. Four bileaflet prostheses, the St. Jude Medical (SJM) valve, the On-X valve with straight leaflets, the Jyros (JR) valve, and the Edwards MIRA (MIRA) valve with curved leaflets, were tested in the mitral position under pulsatile flow conditions to find the effect of the leaflet shape and overall valve design on the flow field, particularly in terms of the turbulent stress distribution, which may influence hemolysis, platelet activation, and thrombus formation. Comparison of the time-resolved flow fields associated with the opening, accelerating, peak, and closing phases of the diastolic flow revealed the effects of the leaflet shape and overall valve design on the flow field. Anatomically and antianatomically oriented bileaflet valves were also compared in the mitral position to study the effects of the orientation on the downstream flow field. The experimental program used a dynamic PIV system utilizing a high-speed, high-resolution video camera to map the true time-resolved velocity field inside the simulated ventricle. Based on the experimental data, the following general conclusions can be made. High-resolution dynamic PIV can capture true chronological changes in the velocity and turbulence fields. In the vertical measuring plane that passes the centers of both the aortic and mitral valves (A-A section), bileaflet valves show clear and simple circulatory flow patterns when the valve is installed in the antianatomical orientation. The SJM, the On-X, and the MIRA valves maintain a relatively high velocity through the central orifice. The curved leaflets of the JR valve generate higher velocities with a divergent flow during the accelerating and peak flow phases when the valve is installed in the anatomical orientation. In the velocity field directly below the mitral valve and normal to the previous measuring plane (B-B section), where characteristic differences in valve design on the three-dimensional flow should be visible, the symmetrical divergent nature of the flow generated by the two inclined half-disks installed in the antianatomical orientation was evident. The SJM valve, with a central downward flow near the valve, is contrasted with the JR valve, which has a peripherally strong downward circulation with higher turbulent stresses. The On-X valve has a strong central downward flow attributable to its large opening angle and flared inlet shape. The MIRA valve also has a relatively strong downward central flow. The MIRA valve, however, diverts the flow three-dimensionally due to its peripherally curved leaflets.

Heart Valve Prosthesis↗
PubMed2005

Assessment of the downstream portion of the mitochondrial pathway of caspase activation in patients with acute myeloid leukemia.

Most chemotherapeutic agents used in the treatment of acute myeloid leukemia (AML) induce apoptosis by triggering the mitochondrial pathway of caspase activation. To investigate the downstream portion of the mitochondrial pathway of caspase activation in patients with AML, cytosolic lysates were stimulated with cytochrome c and dATP and hydrolysis of Ac-DEVD-AFC by effector caspases was measured. Defects in the distal mitochondrial pathway were more common in samples from patients with AML that relapsed rapidly after induction chemotherapy compared to samples from treatment naïve patients. The incidence of blocked pathways did not differ based on response to induction chemotherapy, as even nonresponders generally had an intact pathway. When the distal mitochondrial pathway was blocked, defects were usually at the level of the effector caspases. Thus, functional defects in the distal portion of the mitochondrial pathway of caspase activation may help explain the nature of response and relapse after treatment.

Adenosine Triphosphate↗
PubMed2007

Involvement of caspase-8 in chemotherapy-induced apoptosis of patient derived leukemia cell lines independent of the death receptor pathway and downstream from mitochondria.

Resistance of leukemic cells to chemotherapy frequently occurs in patients with acute leukemia, which may be caused by alterations in common apoptotic pathways. Controversy exists whether cytostatic agents induce the mitochondrial or death receptor pathway of apoptosis. In the mitochondrial pathway cytochrome C release and caspase-9 activation play a central role in the induction of apoptosis, while formation of a Death Inducing Signaling Complex (DISC) and caspase-8 activation have been reported to be essential in death receptor-induced apoptosis. Here, we show in human derived myeloid and lymphoblastic leukemia cell lines that caspase-8 plays a more important role than previously expected in apoptosis mediated via the mitochondrial pathway. We demonstrated in these malignant cells chemotherapy-induced apoptosis independent of the death receptor pathway, since blocking this pathway using a retroviral construct encoding Flice inhibitory protein (FLIP) did not inhibit drug-induced apoptosis or caspase-8 activation, while overexpression of Bcl-2 completely inhibited both events. Furthermore, we showed that activation of caspase-8 by cytostatic agents occurred downstream from mitochondria. Since caspase-8 plays a central role in both death receptor- and chemotherapy-induced apoptosis of malignant cells from patients with acute leukemia, therapeutic strategies focusing at modulation and activation of caspase-8 may be successful in the treatment of drug-resistant malignancies.

Antineoplastic Agents↗
PubMed2006

Characterization of pbpA and pbp2 encoding penicillin-binding proteins located on the downstream of clavulanic acid gene cluster in Streptomyces clavuligerus.

Two genes, pbpA (orf18) and pbp2 (orf19) located on the downstream of clavulanic acid (CA) gene cluster of Streptomyces clavuligerus were cloned into pET-28a(+), and confirmed to encode a family of high molecular-weight penicillin-binding proteins (PBPs). Both genes were amplified from genomic DNA by PCR and expressed in E. coli BL21 (DE3). Hydropathy plots of the proteins revealed a single stretch of hydrophobic amino acids indicating them to be transmembrane proteins. Pbp2 had lower affinity to penicillin G compared to PbpA, and was essential to the cell growth in contrast to PbpA.

Amino Acid Sequence↗
PubMed2005

Elevated levels of cadmium and zinc in paddy soils and elevated levels of cadmium in rice grain downstream of a zinc mineralized area in Thailand: implications for public health.

Prolonged consumption of rice containing elevated cadmium (Cd) levels is a significant health issue particularly in subsistence communities that are dependent on rice produced on-farm. This situation is further exacerbated in areas of known non-ferrous mineralization adjacent to rice-based agricultural systems where the opportunity for contamination of rice and its eventual entry into the food chain is high. In the current study, an assessment of the degree of soil Cd and Zn contamination and associated rice grain Cd contamination downstream of an actively mined zone of Zn mineralization in western Thailand was undertaken. Total soil Cd and Zn concentrations in the rice-based agricultural system investigated ranged from 0.5 to 284 mg kg(-1) and 100 to 8036 mg kg(-1), respectively. Further, the results indicate that the contamination is associated with suspended sediment transported to fields via the irrigation supply. Consequently, the spatial distribution of Cd and Zn is directly related to a field's proximity to primary outlets from in-field irrigation channels and inter-field irrigation flows with 60-100% of the Cd and Zn loading associated with the first three fields in irrigation sequence. Rice grain Cd concentrations in the 524 fields sampled, ranged from 0.05 to 7.7 mg kg(-1). Over 90% of the rice grain samples collected contained Cd at concentrations exceeding the Codex Committee on Food Additives and Contaminants (CCFAC) draft Maximum Permissible Level for rice grain of 0.2 mg Cd kg(-1). In addition, as a function of demographic group, estimated Weekly Intake (WI) values ranged from 20 to 82 mug Cd per kg Body. This poses a significant public health risk to local communities. The results of this study suggest that an irrigation sequence-based field classification technique in combination with strategic soil and rice grain sampling and the estimation of WI values via rice intake alone may be a useful decision support tool to rapidly evaluate potential public health risks in irrigated rice-based agricultural systems receiving Cd contaminated irrigation water. In addition, the proposed technique will facilitate the cost effective strategic targeting of detailed epidemiological studies thus focusing resources to specific 'high risk' areas.

Agriculture↗
PubMed2005

B23 is a downstream target of polyamine-modulated CK2.

Our previous studies have shown that the overexpression of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, increases the enzymatic activity of the polyamine-responsive enzyme casein kinase 2 (CK2). Because CK2 is known to preferentially associate with the nuclear matrix in response to other trophic stimuli, we investigated the effects of ODC overexpression on CK2 localisation and on the CK2-mediated phosphorylation of a known CK2 substrate, the nucleolar phosphoprotein B23. Immunofluorescence analysis of CK2 and B23 in primary keratinocytes revealed that ODC overexpression resulted in the colocalisation of CK2 with B23 at the nucleolar borders. ODC overexpression also increased CK2 kinase activity 2-fold at the nuclear matrix, a response which could be abrogated by treatment of K6/ODC transgenic keratinocytes with the ODC inhibitor alpha-difluoromethylornithine (DFMO). Levels of B23 protein were also elevated in ODC-overexpressing cells compared to normal cells or transgenic cells treated with DFMO. This increase in protein level was neither due to an increase in steady-state mRNA levels, nor was it due to increased stability of B23 protein. Phosphorylation of B23 was also increased in ODC-overexpressing cells, and this increased phosphorylation could be blocked by treatment of the cells with the CK2 kinase inhibitors apigenin or 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). These data suggest that B23 may be a downstream effector of polyamines via phosphorylation by the protein kinase CK2.

Animals↗
PubMed1992

Enhancer-site downstream binding protein activity is enriched in rat tissues that express the class I alcohol dehydrogenase gene.

The activity of the rat class I alcohol dehydrogenase (ADH) is enriched in certain tissues including the liver, intestine and testis. The tissue-specific expression of the gene encoding ADH in the rat was studied and found to closely correlate with tissue isozymic activity. A factor designated enhancer-site downstream binding protein (EDBP) was recently identified in the rat liver and found to interact with the proximal promoter of the class I ADH gene. The distribution of EDBP in nuclear extracts obtained from various tissues was examined based on its sequence-specific DNA binding property and found to correlate with tissue ADH expression. These findings suggest that EDBP is potentially a positive regulatory factor which is involved in controlling the tissue-specific expression of the ADH gene.

Alcohol Dehydrogenase↗
PubMed1992

Cloning and characterization of a novel Drosophila Wnt gene, Dwnt-5, a putative downstream target of the homeobox gene distal-less.

The Wnt gene family in vertebrates comprises at least 11 distinct genes but the only family member previously identified in Drosophila has been the segment polarity gene wingless (wg), the ortholog of vertebrate Wnt-1. In this report we describe the isolation of a novel Drosophila Wnt gene, Dwnt-5, which differs significantly from wg in both the pattern of its expression during embryogenesis and the predicted structure of its product. Dwnt-5 encodes a polypeptide of 112 kDa, which is more than twice as large as the products of previously known Wnt genes. The protein shares homology with other Wnt sequences in its carboxy-terminal half only and is most closely related to the products of vertebrate Wnt-5a and Wnt-5b. Dwnt-5 is expressed in a complex pattern during Drosophila embryogenesis. At the extended germ band stage, however, transcripts accumulate specifically in the nascent limb primordia of the head and thoracic segments. We show that this elevated expression depends on the activity of the homeobox gene Distal-less (Dll) and suggest that the Dwnt-5 gene may constitute a downstream target of Dll that acts in the specification of these primordia.

Amino Acid Sequence↗
PubMed1987

Transcriptional enhancer activity in the variable tandem repeat DNA sequence downstream of the human Ha-ras 1 gene.

A short term transfection technique using the chloramphenicol acetyltransferase gene as an assay system has been employed to examine the presence of transcriptional regulatory sequences within the variable tandem repeat (VTR) DNA sequence located downstream of the human Ha-ras1 gene. Here we find that the VTR sequences possess an endogenous enhancer activity of both the normal and the T24 mutant Ha-ras1 gene.

Animals↗
PubMed1990

The structural gene for cytochrome c551 from Pseudomonas aeruginosa. The nucleotide sequence shows a location downstream of the nitrite reductase gene.

The gene coding for Pseudomonas aeruginosa cytochrome c551 has been cloned and its nucleotide sequence determined. Cytochrome c551 is expressed as a 104 amino acid pre-protein from which a signal peptide of 22 amino acids is cleaved off during the translocation across the cytoplasmic membrane. The gene is located just downstream of the gene coding for nitrite reductase on the Pseudomonas aeruginosa chromosome, suggesting that these genes form an operon.

Amino Acid Sequence↗
PubMed1993

Phosphatidic acid induces the respiratory burst of electropermeabilized human neutrophils by acting on a downstream step of protein kinase C.

Phosphatidic acid (PA) dose-dependently induced superoxide (O2-) production of electropermeabilized human neutrophils but not of intact neutrophils, indicating that PA induces the activation of NADPH oxidase by acting on an intracellular target. The O2- production by PA was not inhibited by protein kinase C (PKC) inhibitors, such as staurosporine and calphostin C, and an inhibitor of PA phosphohydrolase, propranolol. These observations suggest that the activation of the oxidase by PA is independent of the activity of PKC and may dominate the activation by diacylglycerol which is formed from PA via the action of PA phosphohydrolase. Furthermore, the production by PA, as well as that by phorbol myristate acetate, was inhibited by cyclic AMP and GDP beta S. Therefore, PA seems to act at a site downstream of PKC.

Cell Membrane Permeability↗
PubMed1985

In vivo demonstration of flow recirculation and turbulence downstream of graded stenoses in canine arteries.

The velocity field around arterial stenoses was investigated using a pulsed doppler velocimeter in vivo. Asymmetric zones of recirculation were identified by systolic flow reversal in the post-stenotic field in carotid and iliac arteries of anesthetised dogs. There was a close correlation between shear intensity and turbulence as estimated by the velocity difference between the jet and the recirculation zone and by maximum spectral width respectively. Under the conditions of these experiments, stenosis grade (% diameter reduction) dominated hemodynamic variables such as Reynolds number, oscillation and pulsatility in determining the intensity of turbulence. The method used does not appear to have sufficient resolution to distinguish between turbulence and discrete oscillating velocities (vorticity) nor to allow determination of wall shear stress though the pattern of change of the latter is similar to that found downstream of axisymmetric stenosis in models using steady flow.

Animals↗
PubMed1987

Analysis of break frequencies downstream of a constriction in a cylindrical tube.

Experiments were performed to correlate steady-flow power spectra downstream of a stenosis in a cylindrical tube with the flow geometry and velocity. The experiments were motivated by the need to improve quantitative phonoangiography. An objective break frequency (fb) was computed from spectra of velocity fluctuations, as measured with a hot film anemometer. Least squares fits with two independent variables were used to find an empirical relationship between a Strouhal number (S2), the contraction ratio (ds/D) and the Reynolds number (Re). The variables D and ds, are, respectively, the unobstructed tubing diameter and the inner diameter of the stenosis. The relationship found was S2 = Re 0.72(ds/D)0.26 The contraction ratio ds/D, can be found from the empirical relation in terms of known parameters. For the hot wire data the average error between the computed value of ds/D and the known value was 2.3%.

Arterial Occlusive Diseases↗
PubMed1988

Effects of vibration on steady flow downstream of a stenosis.

A physical model was used to test the effects of vibrations on the position of transition to turbulence (zt) downstream of a constriction. Constrictions were inserted in a length of clear plastic (Tygon) tubing and vibrated. Water was the fluid medium and flow was visualized with India ink. The frequency and velocity of vibration were monitored. For a given constriction and flow velocity, there was a band of frequencies which caused zt to move upstream. This band corresponded to frequencies of flow disturbances as measured with a hot-film anemometer without vibration. Both flow-visualization and hot-film frequencies were correlated via a Strouhal number to the Reynolds number and contraction ratio of the flow. Values of zt decreased with increasing vibration amplitude. The critical Reynolds number for turbulence was also decreased by vibration. These results are of importance in the diagnosis of vascular disease and the design of physical models of stenotic flows.

Arterial Occlusive Diseases↗
PubMed1992

Two-dimensional color-mapping of turbulent shear stress distribution downstream of two aortic bioprosthetic valves in vitro.

Since artificial heart valve related complications such as thrombus formation, hemolysis and calcification are considered related to flow disturbances caused by the inserted valve, a thorough hemodynamic characterization of heart valve prostheses is essential. In a pulsatile flow model, fluid velocities were measured one diameter downstream of a Hancock Porcine (HAPO) and a Ionescu-Shiley Pericardial Standard (ISPS) aortic valve. Hot-film anemometry (HFA) was used for velocity measurements at 41 points in the cross-sectional area of the ascending aorta. Three-dimensional visualization of the velocity profiles, at 100 different instants during one mean pump cycle, was performed. Turbulence analysis was performed as a function of time by calculating the axial turbulence energy within 50 ms overlapping time windows during the systole. The turbulent shear stresses were estimated by using the correlation equation between Reynolds normal stress and turbulent (Reynolds) shear stress. The turbulent shear stress distribution was visualized by two-dimensional color-mapping at different instants during one mean pump cycle. Based on the velocity profiles and the turbulent shear stress distribution, a relative blood damage index (RBDI) was calculated. It has the feature of combining the magnitude and exposure time of the estimated shear stresses in one index, covering the entire cross-sectional area. The HAPO valve showed a skewed jet-type velocity profile with the highest velocities towards the left posterior aortic wall. The ISPS valve revealed a more parabolic-shaped velocity profile during systole. The turbulent shear stresses were highest in areas of high or rapidly changing velocity gradients. For the HAPO valve the maximum estimated turbulent shear stress was 194 N m-2 and for the ISPS valve 154 Nm-2. The RBDI was the same for the two valves. The turbulent shear stresses had magnitudes and exposure times that might cause endothelial damage and sublethal or lethal damage to blood corpuscules. The RBDI makes comparison between different heart valves easier and may prove important when making correlation with clinical observations.

Aortic Valve↗
PubMed1996

Wastewater from the manufacture of rubber vulcanization accelerators: characterization, downstream monitoring and chemical treatment.

The content of wastewater resulting from the manufacture of rubber antioxidants and accelerators by a factory situated in the Ebro basin (Spain) has been determined using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-flame ionization detection (GC-FID). The change in the pollutants was studied in the riverbed via two modules which continuously gathered pollutants on various solid supports (activated carbon and XAD-2 resins). These modules were located in Bocal Station, lying a further 100 km downstream from the factory, and from the Zaragoza water supply. Forty-six different compounds were identified at Bocal Station, the majority resulting from the production of rubber additives. Due to the immunity of different waste substances, and to the toxic nature of some, we studied their reaction when subjected to techniques of chemical oxidation using ozone.

Antioxidants↗
PubMed1988

Alternative use of a polyadenylation signal and of a downstream 3' splice site. Effect of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

A minor pathway for the processing of transcripts from the early region 3 transcription unit of adenovirus 2 is described. It results from the selection of a promoter-proximal polyadenylation site P1 instead of the major promotor-distal sites P2 and P4. 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) considerably reduces the use of the major pathways and enhances the minor one. The characterization of three novel nuclear RNAs whose amount increases in DRB-treated cells leads us to propose the following steps for the selection of P1. The nascent transcript is first cleaved in the branch point-3' splice site region of the first E3 IVS (intervening sequence), generating a promoter-proximal RNA with a heterogeneous 3' end (F-RNA) and a promoter-distal RNA with a heterogeneous 5' end (G-RNA). This cleavage prevents the formation of the premessenger RNAs ending at P2 and P4. The 3' end of F-RNA is about 130 nucleotides downstream from P1 and F-RNA contains the signals required for cleavage-polyadenylation. It may thus generate CP1, which is the transcript ending at P1. The cleavage of the nascent transcript in a region crucial for spliceosome assembly suggests that defective assembly may render RNA sequences at the 3' end of IVS accessible to intracellular nucleases and trigger the use of an upstream polyadenylation site. Such a mechanism may explain the alternative use of neighbouring, mutually exclusive, splice and polyadenylation sites.

Adenoviridae↗