[Eradication of high-grade dysplasia in Barrett esophagus by photodynamic therapy with endogenously generated protoporphyrin IX].
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Aged↗
Biomedical subjects
M Ortner
Publications and source records attributed to M Ortner.
Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease.
BACKGROUND: In Crohn's disease, inflammation is presumably sustained by an increased production of proinflammatory cytokines, in particular tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce a host of cellular effector events resulting in perpetuation of the inflammatory process. In vivo studies with anti-TNF alpha antibody treatment have led to impressive clinical results. AIMS: To investigate whether treatment with the TNF alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid dependent chronic active Crohn's disease. METHODS: Sixteen Crohn's disease patients received oxpentifylline 400 mg four times a day in a four week open label study. RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohn's disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor oxpentifylline does not improve inflammation in Crohn's disease. This finding suggests that there may be more key mediators than only TNF alpha in the inflammatory process in Crohn's disease.
Adult↗
Molecular and structural analysis of a continuous birch profilin epitope defined by a monoclonal antibody.
The interaction of a mouse monoclonal antibody (4A6) and birch profilin, a structurally well conserved actin- and phosphoinositide-binding protein and cross-reactive allergen, was characterized. In contrast to serum IgE from allergic patients, which shows cross-reactivity with most plants, monoclonal antibody 4A6 selectively reacted with tree pollen profilins. Using synthetic overlapping peptides, a continuous hexapeptide epitope was identified. The exchange of a single amino acid (Gln-47 --> Glu) within the epitope was found to abolish the binding of monoclonal antibody 4A6 to other plant profilins. The NMR analyses of the birch and the nonreactive timothy grass profilin peptides showed that the loss of binding was not due to major structural differences. Both peptides adopted extended conformations similar to that observed for the epitope in the x-ray crystal structure of the native birch profilin. Binding studies with peptides and birch profilin mutants generated by in vitro mutagenesis demonstrated that the change of Gln-47 to acidic amino acids (e.g. Glu or Asp) led to electrostatic repulsion of monoclonal antibody 4A6. In conclusion the molecular and structural analyses of the interaction of a monoclonal antibody with a continuous peptide epitope, recognized in a conformation similar to that displayed on the native protein, are presented.
Allergens↗
Helmholtz free energies of atom pair interactions in proteins.
BACKGROUND: Proteins fold to unique three-dimensional structures, but how they achieve this transition and how they maintain their native folds is controversial. Information on the functional form of molecular interactions is required to address these issues. The basic building blocks are the free energies of atom pair interactions in dense protein solvent systems. In a dense medium, entropic effects often dominate over internal energies but free energy estimates are notoriously difficult to obtain. A prominent example is the peptide hydrogen bond (H-bond). It is still unclear to what extent H-bonds contribute to protein folding and stability of native structures. RESULTS: Radial distribution functions of atom pair interactions are compiled from a database of known protein folds. The functions are transformed to Helmholtz free energies using a recipe from the statistical mechanics of dense interacting systems. In particular we concentrate on the features of the free energy functions of peptide H-bonds. Differences in Helmholtz free energies correspond to the reversible work required or gained when the distance between two particles is changed. Consequently, the functions directly display the energetic features of the respective thermodynamic process, such as H-bond formation or disruption. CONCLUSIONS: In the H-bond potential, a high barrier isolates a deep narrow minimum at H-bond contact from large distances, but the free energy difference between H-bond contact and large distances is close to zero. The energy barrier plays an intriguing role in H-bond formation and disruption: both processes require activation energy in the order of 2kT. H-bond formation opposes folding to compact states, but once formed, H-bonds act as molecular locks and a network of such bonds keeps polypeptide chains in a precise spatial configuration. On the other hand, peptide H-bonds do not contribute to the thermodynamic stability of native folds, because the energy balance of H-bond formation is close to zero.
Drug Stability↗
Multiple fistulas and tracheobronchial stenoses require extensive stenting of the central airways and esophagus in squamous-cell carcinoma.
We report here on two cases of double airway and esophageal stenting in patients with multiple esophagotracheal fistulas and stenoses of the airways and esophagus due to squamous-cell carcinoma. Dumon stents and a Strecker device were used for tracheobronchial stenting. Covered Gianturco Z-stents were implanted into the esophagus. In one case, extrinsic compression of the trachea and tumor progression required recanalization by Nd:YAG laser. Clinical improvement led to discharge of the patients within two weeks after the procedure. The results show that simultaneous implantation of stents in the central airways and covered Gianturco Z-stents in the esophagus is an effective therapeutic strategy in patients with tracheal and esophageal obstructions and esophagorespiratory fistulas. Further systematic studies evaluating double stenting are warranted.
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Progress in fold recognition.
The prediction experiment reveals that fold recognition has become a powerful tool in structural biology. We applied our fold recognition technique to 13 target sequences. In two cases, replication terminating protein and prosequence of subtilisin, the predicted structures are very similar to the experimentally determined folds. For the first time, in a public blind test, the unknown structures of proteins have been predicted ahead of experiment to an accuracy approaching molecular detail. In two other cases the approximate folds have been predicted correctly. According to the assessors there were 12 recognizable folds among the target proteins. In our postprediction analysis we find that in 7 cases our fold recognition technique is successful. In several of the remaining cases the predicted folds have interesting features in common with the experimental results. We present our procedure, discuss the results, and comment on several fundamental and technical problems encountered in fold recognition.
Algorithms↗
A respirometer for investigating oxidative cell metabolism: toward optimization of respiratory studies.
Oxygen flux measurements are critical at low rates of. respiration and at oxygen tensions below air saturation. Difficulties are primarily due to increased oxygen diffusion and consumption processes which may occur in conventional closed respirometric chambers. To avoid measurement errors encountered with standard equipment, a new type of oxygraph was developed. This instrument provides reliable quantification of oxygen flux in small organisms, tissue samples, cells, isolated mitochondria, and chloroplasts. The instrument is available commercially or can be rebuilt in a well-equipped laboratory workshop.
Cells↗
Reversibility of oxygen switch-off effect on Bacillus polymyxa nitrogenase.
The objective of this study was to analyse in vivo the effect of oxygen on the nitrogenase of Bacillus polymyxa. The culture technique employed in this study prevented spore formation by B. polymyxa during the entire period of exposure to acetylene. Under these conditions the acetylene-reduction assay allowed quantification of nitrogenase activity over long incubation periods (44 h). Nitrogenase activity was highest in cells harvested in the late logarithmic phase. At PO2 of 0.19 and 0.37 kPa, acetylene reduction was inhibited by 80 and 100%, respectively. This switch-off effect could be reversed through oxygen exhaustion, either by flushing the culture with N2 or by cellular respiration, suggesting a respiratory protection mechanism for the nitrogenase complex in B. polymyxa. Oxygen consumption measured by a closed-chamber respirometer showed a linear increase up to a PO2 of 0.2 kPa. Above 0.3 kPa a saturation in oxygen consumption was observed. Exposure to high oxygen pressures resulted in an irreversible loss of nitrogenase activity. The oxygen inhibition pattern was shown to be similar to that in other microaerophilic and anaerobic nitrogen-fixing microorganisms.
Bacillus↗