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Biomedical subjects

E Beck

Publications and source records attributed to E Beck.

At least 19 recordsLinked to original sources

Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial.

OBJECTIVES: To assess the effect of sulfasalazine (SSZ) on inflammatory back pain (IBP) due to active undifferentiated spondyloarthritis (uSpA) or ankylosing spondylitis in patients with symptom duration <5 years. METHODS: Patients with IBP and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >3 from 12 centres were randomly assigned to 24 weeks' treatment with SSZ 2 g/day or placebo. The primary outcome variable was the change in BASDAI over 6 months. Secondary outcomes included measures of spinal pain, physical function and inflammation. RESULTS: 230 patients (50% men, age range 18-64 years, 67% human leucocyte antigen B27 positive) were treated with either SSZ 2x1 g/day or placebo for 6 months. Enthesitis was found in 50%, and peripheral arthritis in 47% of the patients. The mean (SD) BASDAI dropped markedly in both groups: by 3.7 (2.7) and 3.8 (2.4), respectively, as did most secondary outcome measures. No noticeable difference in treatment was observed between groups. Patients with IBP and no peripheral arthritis had significantly (p = 0.03) more benefit with SSZ (BASDAI 5.1 (1.3) to 2.8 (2.3)) than with placebo (5.2 (1.6) to 3.8 (2.4)). Spinal pain (p = 0.03) and morning stiffness (p = 0.05) improved with SSZ in these patients, but other secondary outcomes were not markedly different. CONCLUSION: SSZ was no better than placebo for the treatment of the signs and symptoms of uSpA; however, SSZ was more effective than placebo in the subgroup of patients with IBP and no peripheral arthritis.

Adolescent↗

Seasonality of weather and tree phenology in a tropical evergreen mountain rain forest.

Flowering and fruiting as phenological events of 12 tree species in an evergreen tropical mountain rain forest in southern Ecuador were examined over a period of 3-4 years. Leaf shedding of two species was observed for 12 months. Parallel to the phenological recordings, meteorological parameters were monitored in detail and related to the flowering and fruiting activity of the trees. In spite of the perhumid climate of that area, a high degree of intra- and inter-specific synchronisation of phenological traits was apparent. With the exception of one species that flowered more or less continuously, two groups of trees could be observed, one of which flowered during the less humid months (September to October) while the second group started to initiate flowers towards the end of that phase and flowered during the heavy rains (April to July). As reflected by correlation coefficients, the all-time series of meteorological parameters showed a distinct seasonality of 8-12 months, apparently following the quasi-periodic oscillation of precipitation and related cloudiness. As revealed by power spectrum analysis and Markov persistence, rainfall and minimum temperature appear to be the only parameters with a periodicity free of long-term variations. The phenological events of most of the plant species showed a similar periodicity of 8-12 months, which followed the annual oscillation of relatively less and more humid periods and thus was in phase or in counter-phase with the oscillations of the meteorological parameters. Periods of unusual cold or dryness, presumably resulting from underlying longer-term trends or oscillations (such as ENSO), affected the homogeneity of quasi-12-month flowering events, fruit maturation and also the production of germinable seeds. Some species show underlying quasi-2-year-oscillations, for example that synchronise with the development of air temperature; others reveal an underlying decrease or increase in flowering activity over the observation period, influenced for instance by solar irradiance. As Ecuador suffers the highest rate of deforestation in South America, there is an urgent need for indigenous plant material for reforestation. A detailed knowledge of the biology of reproduction in relation to governing external factors (mainly climate) is thus required.

Altitude↗

Crosstalk between auxin, cytokinins, and sugars in the plant cell cycle.

Plant meristems are utilization sinks, in which cell division activity governs sink strength. However, the molecular mechanisms by which cell division activity and sink strength are adjusted to a plant's developmental program in its environmental setting are not well understood. Mitogenic hormonal as well as metabolic signals drive and modulate the cell cycle, but a coherent idea of how this is accomplished, is still missing. Auxin and cytokinins are known as endogenous mitogens whose concentrations and timing, however, can be externally affected. Although the sites and mechanisms of signal interaction in cell cycle control have not yet been unravelled, crosstalk of sugar and phytohormone signals could be localized to several biochemical levels. At the expression level of cell cycle control genes, like cyclins, Cdks, and others, synergistic but also antagonistic interactions could be demonstrated. Another level of crosstalk is that of signal generation or modulation. Cytokinins affect the activity of extracellular invertases and hexose-uptake carriers and thus impinge on an intracellular sugar signal. With tobacco BY-2 cells, a coordinated control of cell cycle activity at both regulatory levels could be shown. Comparison of the results obtained with the root cell-representing BY-2 cells with literature data from shoot tissues or green cell cultures of Arabidopsis and Chenopodium suggests opposed and tissue-specific regulatory patterns of mitogenic signals and signal crosstalk in root and shoot meristems.

Arabidopsis↗

Endogenous cytokinin oscillations control cell cycle progression of tobacco BY-2 cells.

The significance of cytokinins for the progression of the cell cycle is well known. Cytokinins contribute to the control of the expression of D-cyclins and other cell cycle genes, but knowledge as to how they affect the progression of the cell cycle is still limited. Highly synchronized tobacco BY-2 cells with clearly defined cell cycle stages were employed to determine cytokinin patterns in detail throughout the entire cycle. Concentrations of trans-zeatin, and of some other cytokinins, oscillated during the course of the cell cycle, increasing substantially at all four phase transitions and decreasing again to a minimum value during the course of each subsequent phase. Addition of exogenous cytokinins or inhibition of cytokinin biosynthesis promoted the progression of the cell cycle when the effects of these manipulations intensified the endogenous fluctuations, whereas the progression of the cycle was retarded when the amplitude of the fluctuations was decreased. The results show that the attainment of low concentrations of cytokinins is as important as the transient increases in concentration for a controlled progression from one phase of the cell cycle to the next. Cytokinin oxidase/dehydrogenase activity also showed fluctuations during the course of the cell cycle, the timing of which could at least partly explain oscillations of cytokinin levels. The activities of the enzyme were sufficient to account for the rates of cytokinin disappearance observed subsequent to a phase transition.

Aphidicolin↗

Investigation of the aluminium biokinetics in humans: a 26Al tracer study.

Despite the well-known toxicity of aluminium in chronic renal failure, a solid database on its biokinetics has been difficult to establish. A highly sensitive method using (26)Al as tracer and accelerator mass spectrometry (AMS) for detection was used. No perturbing background and saturation effects were taken into account using a delta function input of aluminium in time. Aluminium absorption, distribution, speciation and excretion in six healthy volunteers and in two patients with chronic renal failure were investigated following administration of a single oral or i.v. dose of (26)Al. Serial samples of blood and urine were taken. In a speciation study, the time dependence of the binding of (26)Al to low-molecular weight molecules in serum was investigated. The measured data were compared and interpreted with simulations in an open compartmental model. Fractional absorption, distribution, excretion and time constants for the aluminium transport were determined. Typical intestinal absorption rates for AlCl(3) were found to be in the range of 10(-3). The ultrafiltrable percentage of aluminium in serum of one volunteer was estimated to be 5.6+/-0.8%. Differences between healthy volunteers and patients with chronic renal failure were deduced. The employed method using (26)Al and ams has proven to be highly sensitive for investigations of aluminium biokinetics at the ultra-trace element level. With the model, the measured values of (26)Al in serum and urine were used to precisely determine absorption, speciation, distribution, retention and excretion of aluminium in humans.

Administration, Oral↗

Improved delivery of ipratropium bromide/fenoterol from Respimat Soft Mist Inhaler in patients with COPD.

We performed a multicentre, randomised, double-blind (within-device), placebo- and active-controlled, parallel-group study to compare the efficacy and safety of ipratropium bromide plus fenoterol hydrobromide (IB/FEN; Berodual) delivered via the novel, propellant-free Respimat Soft Mist Inhaler (SMI) and from a chlorofluorocarbon (CFC)-metered-dose inhaler (MDI) in moderate-to-severe chronic obstructive pulmonary disease (COPD) patients. After 2-weeks' run-in (CFC-MDI [IB 20 microg/FEN 50 microg per actuation] two actuations q.i.d. [MDI 40/100]), 892 patients were randomised to Respimat SMI containing IB 10 microg/FEN 25 microg (Respimat SMI 10/25), IB 20 microg/FEN 50 microg (Respimat SMI 20/50) or placebo (one actuation q.i.d.), or a CFC-MDI containing IB 20 microg/FEN 50 microg (MDI 40/100) or placebo (two actuations q.i.d.) for 12 weeks. Analysis of the primary endpoint (change in forced expiratory volume in 1 s [FEV1] in the first 60 min after dosing [area under the curve; AUC0-1h]) on day 85 showed that the efficacy of Respimat SMI 20/50 (but not Respimat SMI 10/25) was not inferior to that of MDI 40/100. The safety profile of Respimat SMI was comparable to CFC-MDI. Switching from MDI 40/100 to Respimat SMI was well tolerated. Respimat SMI enables a 50% reduction of the nominal inhaled dose of IB/FEN in COPD patients while offering similar therapeutic efficacy and safety to the CFC-MDI.

Administration, Inhalation↗

Identification of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate as a major activator for human gammadelta T cells in Escherichia coli.

The gcpE and lytB gene products control the terminal steps of isoprenoid biosynthesis via the 2-C-methyl-D-erythritol 4-phosphate pathway in Escherichia coli. In lytB-deficient mutants, a highly immunogenic compound accumulates significantly, compared to wild-type E. coli, but is apparently absent in gcpE-deficient mutants. Here, this compound was purified from E. coli DeltalytB mutants by preparative anion exchange chromatography, and identified by mass spectrometry, (1)H, (13)C and (31)P NMR spectroscopy, and NOESY analysis as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP). HMB-PP is 10(4) times more potent in activating human Vgamma9/Vdelta2 T cells than isopentenyl pyrophosphate.

Bacterial Proteins↗

Activation of spinach pullulanase by reduction results in a decrease in the number of isomeric forms.

Spinach starch debranching enzyme, a limit dextrinase or pullulanase (EC 3.2.1.41), is a monomeric protein of 100 kDa that produces up to seven coexisting and mutually interconvertible isomers of different specific activity, a phenomenon that has been termed microheterogeneity and for which a structural explanation has not yet been presented. The enzyme can be activated by reduction, in particular by thiol reagents, and inactivated by oxidation and the concomitant change of the patterns of its isomeric forms could be quantified by chromatofocusing. The hypothesis was examined that reduction of the enzyme's thiol groups shifts the isomer pattern towards the forms with a higher specific activity while oxidation favours the less active forms. Using TCEP as reductant only the form with the highest specific activity was obtained. This form was almost inaccessible for proteolysis by trypsin while the oxidized and GSH-activated enzyme yielded four peptides when treated with trypsin. Their sequence indicated cleavage predominantly of loops connecting the beta-strands and alpha-helices of the (beta/alpha)(8)-barrel which forms the catalytic site of the pullulanase. Formation of various disulphide bridges between the loops connecting the barrel structures -- predominantly on one side -- may be the reason for the microheterogeneity of the spinach pullulanase. In vivo, the enzyme maintains its activated state due to the high concentration of GSH in the chloroplast. However, the chloroplast's pH shifts from day (pH 8) to night (pH 7) and thus could also alter the activity of the protein in accordance with the required function in starch metabolism.

Chloroplasts↗

LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli.

The mevalonate-independent 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis is essential in many eubacteria, plants, and the malaria parasite. Using genetically engineered Escherichia coli cells able to utilize exogenously provided mevalonate for isoprenoid biosynthesis by the mevalonate pathway we demonstrate that the lytB gene is involved in the trunk line of the MEP pathway. Cells deleted for the essential lytB gene were viable only if the medium was supplemented with mevalonate or the cells were complemented with an episomal copy of lytB.

Animals↗

Diaryl ester prodrugs of FR900098 with improved in vivo antimalarial activity.

The fosmidomycin derivative FR900098 represents an inhibitor of the 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase with potent antimalarial activity. Prodrugs of FR900098 with increased activity after oral administration were obtained by chemical modification of the phosphonate moiety to yield phosphodiaryl esters. One diaryl ester prodrug demonstrated efficacy in mice infected with the rodent malaria parasite Plasmodium vinckei comparable to i.p. drug administration.

Aldose-Ketose Isomerases↗

Cutting edge: human gamma delta T cells are activated by intermediates of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis.

Activation of V gamma 9/V delta 2 T cells by small nonprotein Ags is frequently observed after infection with various viruses, bacteria, and eukaryotic parasites. We suggested earlier that compounds synthesized by the 2-C:-methyl-D-erythritol 4-phosphate (MEP) pathway of isopentenyl pyrophosphate synthesis are responsible for the V gamma 9/V delta 2 T cell reactivity of many pathogens. Using genetically engineered Escherichia coli knockout strains, we now demonstrate that the ability of E. coli extracts to stimulate gamma delta T cell proliferation is abrogated when genes coding for essential enzymes of the MEP pathway, dxr or gcpE, are disrupted or deleted from the bacterial genome.

Aldose-Ketose Isomerases↗

Predictors of depression in a sample of African-American homeless men: identifying effective coping strategies given varying levels of daily stressors.

In a sample of African-American, homeless or insecurely sheltered men, the occurrence of discrete stressors in the prior week contributed to the experience of depressive symptoms among this generally stressed population. Reliance on active, problem-focused coping strategies as opposed to emotion-coping strategies was associated with lower levels of depressive symptoms contradicting the hypothesis that active coping is counter-productive for African-American men. However, depressive symptoms increased, with added uncontrollable stress, even for active copers, contradicting a stress-buffering hypothesis. Under conditions of high uncontrollable stress, problem-focused coping was associated with lower levels of depressive symptoms than emotion-focused coping, however, additional discrete stressors exerted less impact on the level of depressive symptoms among the emotion-focused copers than the active, problem-focused copers.

Adaptation, Psychological↗

GcpE is involved in the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli.

In a variety of organisms, including plants and several eubacteria, isoprenoids are synthesized by the mevalonate-independent 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Although different enzymes of this pathway have been described, the terminal biosynthetic steps of the MEP pathway have not been fully elucidated. In this work, we demonstrate that the gcpE gene of Escherichia coli is involved in this pathway. E. coli cells were genetically engineered to utilize exogenously provided mevalonate for isoprenoid biosynthesis by the mevalonate pathway. These cells were then deleted for the essential gcpE gene and were viable only if the medium was supplemented with mevalonate or the cells were complemented with an episomal copy of gcpE.

Amino Acid Sequence↗

Compartmental model for aluminium biokinetics.

An open compartmental model for describing aluminium biokinetics is presented with a central compartment consisting of transferrin- and citrate-bound aluminium in blood plasma and interstitial fluid, and three peripheral compartments for organs, muscles and bones and the gastro-intestinal tract. The rate constants describing the transport of aluminium are normalized to an estimated plasma volume and do not depend on the size of the individual. Effects due to changes in compartmental sizes or to transport characteristics are described. The model is applied to biokinetics studies of a volunteer after i.v. administration and of Sprague-Dawley rats with different iron status and with nephrectomization after p.o. administration of 26Al.

Absorption↗

Translation from the internal ribosome entry site of bovine viral diarrhea virus is independent of the interaction with polypyrimidine tract-binding protein.

Translation of the pestiviral polyprotein is initiated cap independently at an internal site of the viral RNA, the internal ribosome entry site (IRES). We investigated the translation from the IRES of bovine viral diarrhea virus (BVDV) and the possible interaction of the unconventional cellular RNA-binding proteins, particularly of polypyrimidine tract-binding protein (PTB). The BVDV IRES is translationally active in rabbit reticulocyte lysate (RRL), and it is translated most efficiently at low concentrations of Mg(2+)- and K(+)-ions. In the UV cross-link assay, several proteins from RRL bind to the BVDV IRES, including proteins of 50, 65 and 72kDa, but no protein of 57kDa possibly corresponding to PTB, although PTB is endogenously present in RRL. However, the BVDV IRES can bind PTB weakly under certain conditions. Interestingly, in a functional depletion and add-back translation system, PTB does not enhance translation of BVDV, although PTB enhances translation of a picornavirus in this translation stimulation assay. These results indicate that PTB can bind the BVDV IRES RNA, but translation is independent of the action of PTB.

Animals↗