[Aspects of pulmonary involvement in inflammatory bowel disease]. / Lungenbeteiligung bei chronisch-entzündlichen Darmerkrankungen.

The incidence of pulmonary manifestations of inflammatory bowel disease (IBD) appears to be much higher than previously assumed. In prospective studies, subclinical pulmonary interstitial infiltrates or pathological lung function were found in 40%-60% of IBD patients, both in children and adults. Pulmonary disorders can affect any part of the respiratory system, the most frequent pattern being inflammation of the large airways often associated with bronchiectasis. The differential diagnosis should include drug-related pulmonary disease and infectious causes when receiving immunosuppressive therapy. The diagnostic approach consists of a thorough history and clinical status as well as lung function tests including body plethysmography and high-resolution computed tomography of the thorax. Bronchoscopy with broncheoalveolar lavage and sample collection for histology as well as exclusion of pulmonary embolism may be indicated. Pulmonary disease in association with IBD can develop at any time during the course of IBD: in rare cases, symptoms can evolve even before gastrointestinal symptoms appear. On the other hand, there are frequent reports on the occurrence of pulmonary inflammation after proctocolectomy in patients with ulcerative colitis. The pathophysiologic background is largely unknown, but there seems to be an interaction between gastrointestinal and pulmonary inflammation. The mainstay of therapy are inhaled or systemic corticosteroids. Most patterns of pulmonary involvement in IBD respond well to corticosteroid therapy. Rarely, serious and persisting complications occur, such as strictures or stenosis of the large airways.

Hyperpolarized 133Cs is a sensitive probe for real-time monitoring of biophysical environments.

133Cs NMR is a valuable tool for non-invasive analysis of biological systems, where chemical shift and relaxation properties report on changes in the physical environment. Hyperpolarization can increase the liquid-state 133Cs NMR signal by several orders of magnitude and allow real-time monitoring of physical changes in cell based systems.

In vivo and in vitro liver cancer metabolism observed with hyperpolarized [5-(13)C]glutamine.

Glutamine metabolism is, with its many links to oncogene expression, considered a crucial step in cancer metabolism and it is thereby a key target for alteration in cancer development. In particular, strong correlations have been reported between oncogene expression and expression and activity of the enzyme glutaminase. This mitochondrial enzyme, which is responsible for the deamidation of glutamine to form glutamate, is overexpressed in many tumour tissues. In animal models, glutaminase expression is correlated with tumour growth rate and it is readily possible to limit tumour growth by suppression of glutaminase activity. In principle, hyperpolarized (13)C MR spectroscopy can provide insight to glutamine metabolism and should hence be a valuable tool to study changes in glutaminase activity as tumours progress. However, no such successful in vivo studies have been reported, even though several good biological models have been tested. This may, at least partly, be due to problems in preparing glutamine for hyperpolarization. This paper reports a new and improved preparation of hyperpolarized [5-(13)C]glutamine, which provides a highly sensitive (13)C MR marker. With this preparation of hyperpolarized [5-(13)C]glutamine, glutaminase activity in vivo in a rat liver tumour was investigated. Moreover, this marker was also used to measure response to drug treatment in vitro in cancer cells. These examples of [5-(13)C]glutamine used in tumour models warrant the new preparation to allow metabolic studies with this conditionally essential amino acid.

Pressure-Induced Invar Behavior in Pd3Fe.

Synchrotron x-ray diffraction (XRD) measurements, nuclear forward scattering (NFS) measurements, and density functional theory (DFT) calculations were performed on L1_{2}-ordered Pd3Fe. Measurements were performed at 300 K at pressures up to 33 GPa, and at 7 GPa at temperatures up to 650 K. The NFS revealed a collapse of the 57Fe magnetic moment between 8.9 and 12.3 GPa at 300 K, coinciding with a transition in bulk modulus found by XRD. Heating the sample under a pressure of 7 GPa showed negligible thermal expansion from 300 to 523 K, demonstrating Invar behavior. Zero-temperature DFT calculations identified a ferromagnetic ground state and showed several antiferromagnetic states had comparable energies at pressures above 20 GPa.

X-ray Bragg diffraction in asymmetric backscattering geometry.

We observe three effects in the Bragg diffraction of x rays in backscattering geometry from asymmetrically cut crystals. First, exact Bragg backscattering takes place not at normal incidence to the reflecting atomic planes. Second, a well-collimated (approximately 1 microrad) beam is transformed after the Bragg reflection into a strongly divergent beam (230 microrad) with reflection angle dependent on x-ray wavelength--an effect of angular dispersion. The asymmetrically cut crystal thus behaves like an optical prism, dispersing an incident collimated polychromatic beam. The dispersion rate is approximately 8.5 mrad/eV. Third, parasitic Bragg reflections accompanying Bragg backreflection are suppressed. These effects offer a radically new means for monochromatization of x rays not limited by the intrinsic width of the Bragg reflection.

X-ray interferometry with microelectronvolt resolution.

We demonstrate an interferometer for hard x rays with two back-reflecting sapphire crystal mirrors--a prototype x-ray Fabry-Pérot interferometer. A finesse of 15 and 0.76 mu eV broad Fabry-Pérot transmission resonances are measured by the time response of the interferometer. Interference patterns are observed directly in spectral dependences of reflectivity.

Anomalous isotopic effect on the lattice parameter of silicon.

The difference Delta(a)=a(30)-a(28) of the lattice parameter of 30Si and 28Si crystals is measured over a temperature range from 4.7 to 700 K. In disagreement with existing knowledge, the strongest isotopic effect is not detected at the lowest achieved temperature T=4.7 K. An anomalous behavior is observed: The relative difference |Delta(a)/a| attains its maximum value of 56.8(5) ppm at T=75(10) K. The anomalous behavior is attributed to the influence of phonon modes with negative Grüneisen parameters. At T=700 K the effect still amounts to 30% of the maximal value. The experimental data are consistent with an approach based on the density-functional perturbation theory.

Barley lipid transfer protein, LTP1, contains a new type of lipid-like post-translational modification.

In plants a group of proteins termed nonspecific lipid transfer proteins are found. These proteins bind and catalyze transfer of lipids in vitro, but their in vivo function is unknown. They have been suggested to be involved in different aspects of plant physiology and cell biology, including the formation of cutin and involvement in stress and pathogen responses, but there is yet no direct demonstration of an in vivo function. We have found and characterized a novel post-translational modification of the barley nonspecific lipid transfer protein, LTP1. The protein-modification bond is of a new type in which an aspartic acid in LTP1 is bound to the modification through what most likely is an ester bond. The chemical structure of the modification has been characterized by means of two-dimensional homo- and heteronuclear nuclear magnetic resonance spectroscopy as well as mass spectrometry and is found to be lipid-like in nature. The modification does not resemble any standard lipid post-translational modification but is similar to a compound with known antimicrobial activity.

gamma-Ray wavelength standard for atomic scales.

The wavelength of the 57Fe Mössbauer radiation is measured with a relative uncertainty of 0.19 ppm by using almost exact Bragg backscattering from a reference silicon crystal. Its value is determined as lambda(M) = 0.860 254 74(16)x10(-10) m. The corresponding Mössbauer photon energy is E(M) = 14 412.497(3) eV. The wavelength of the 57Fe Mössbauer radiation is easily reproducible with an accuracy of at least 10(-11)lambda(M) and could be used as a length standard of atomic dimensions.

Identification of a neuritogenic ligand of the neural cell adhesion molecule using a combinatorial library of synthetic peptides.

The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and learning. In this study, we identified a synthetic peptide-ligand of the NCAM Ig1 module by combinatorial chemistry and showed it could modulate NCAM-mediated cell adhesion and signal transduction with high potency. In cultures of dissociated neurons, this peptide, termed C3, stimulated neurite outgrowth by activating a signaling pathway identical to that activated by homophilic NCAM binding. A similar effect was shown for the NCAM Ig2 module, the endogenous ligand of NCAM Ig1. By nuclear magnetic resonance spectroscopy, the C3 binding site in the NCAM Ig1 module was mapped and shown to be different from the binding site of the NCAM Ig2 module. The C3 peptide may prove useful as a lead in development of therapies for neurodegenerative disorders, and the C3 binding site of NCAM Ig1 may represent a target for discovery of nonpeptide drugs.

Pulse sequences for measurement of one-bond (15)N-(1)H coupling constants in the protein backbone.

A set of three improved two-dimensional (2D) NMR methods for measuring one-bond (15)N-(1)H coupling constants in the protein backbone is presented. They are tailored to suit the size of the TROSY effect, i.e., the degree of interference between dipolar and chemical shift anisotropy relaxation mechanisms. The methods edit 2D spectra into two separate subspectra corresponding to the two possible spin states of the coupling partner. Cross talk between the two subspectra is a second order effect in the difference between the actual coupling constants and the one used in setting the pertinent delays of the pulse sequences. This relatively high degree of editing accuracy makes the methods useful for applications to molecules subjected to weak alignment where the one-bond coupling constants are linear combinations of a scalar J and a residual dipolar contribution containing important structural information. A demonstration of the new methods is shown for the (15)N-labeled protein chymotrypsin inhibitor 2 in a lipid bicelle mixture.

Solution structure of barley lipid transfer protein complexed with palmitate. Two different binding modes of palmitate in the homologous maize and barley nonspecific lipid transfer proteins.

The structure of a nonspecific lipid transfer protein from barley (ns-LTPbarley) in complex with palmitate has been determined by NMR spectroscopy. The structure has been compared to the structure of ns-LTPbarley in the absence of palmitate, to the structure of ns-LTPbarley in complex with palmitoyl coenzyme A, to the structure of ns-LTPmaize in its free form, and to the maize protein complexed with palmitate. Binding of palmitate only affects the structure of ns-LTPbarley moderately in contrast to the binding of palmitoyl coenzyme A, which leads to a considerable expansion of the protein. The modes of binding palmitate to the maize and barley protein are different. Although in neither case there are major conformational changes in the protein, the orientation of the palmitate in the two proteins is exactly opposite.

Barley lipid-transfer protein complexed with palmitoyl CoA: the structure reveals a hydrophobic binding site that can expand to fit both large and small lipid-like ligands.

BACKGROUND: . Plant nonspecific lipid-transfer proteins (nsLTPs) bind a variety of very different lipids in vitro, including phospholipids, glycolipids, fatty acids and acyl coenzyme As. In this study we have determined the structure of a nsLTP complexed with palmitoyl coenzyme A (PCoA) in order to further our understanding of the structural mechanism of the broad specificity of these proteins and its relation to the function of nsLTPs in vivo. RESULTS: . 1H and 13C nuclear magnetic resonance spectroscopy (NMR) have been used to study the complex between a nsLTP isolated from barley seeds (bLTP) and the ligand PCoA. The resonances of 97% of the 1H atoms were assigned for the complexed bLTP and nearly all of the resonances were assigned in the bound PCoA ligand. The palmitoyl chain of the ligand was uniformly 13C-labelled allowing the two ends of the hydrocarbon chain to be assigned. The comparison of a subset of 20 calculated structures to an average structure showed root mean square deviations of 1.89 +/- 0.19 for all C, N, O, P and S atoms of the entire complex and of 0.57 +/- 0.09 for the peptide backbone atoms of the four alpha helices of the complexed bLTP. The four-helix topology of the uncomplexed bLTP is maintained in the complexed form of the protein. The bLTP only binds the hydrophobic parts of PCoA with the rest of the ligand remaining exposed to the solvent. The palmitoyl chain moiety of the ligand is placed in the interior of the protein and bent in a U-shape. This part of the ligand is completely buried within a hydrophobic pocket of the protein. CONCLUSIONS: . A comparison of the structures of bLTP in the free and bound forms suggests that bLTP can accommodate long olefinic ligands by expansion of the hydrophobic binding site. This expansion is achieved by a bend of one helix, HA, and by conformational changes in both the C terminus and helix HC. This mode of binding is different from that seen in the structure of maize nsLTP in complex with palmitic acid, where binding of the ligand is not associated with structural changes.

[The incidence of lung infection in patients with mucoviscidosis and the disease course with various pathogen spectra]. / Zur Häufigkeit der Lungeninfektion bei Patienten mit Mukoviszidose und zum Krankheitsverlauf bei unterschiedlichem Erregerspektrum.

A retrospective review on the frequency of lung infections by the most important organisms Staphylococcus aureus and Pseudomonas aeruginosa in patients with cystic fibrosis in the GDR during the period from 1981 to 1985 revealed an average infectious rate of 58.6 per cent by Staphylococcus and of 26.9 per cent by Pseudomonas respectively. A distinct increase of the infections by Pseudomonas could only be documented from 1981 to 1982, later on the infectious rate remained nearly equal and showed only a peak value of 35.6 per cent in 1983. Thus the frequency of infections by Pseudomonas is significantly lower in the GDR than in most other countries. The comparison of the course of the disease in patients with permanent lung infection during 4 or 5 years established a mortality rate of a double amount in the group of patients with Pseudomonas colonisation versus the group with Staphylococcus colonisation. Otherwise no significant difference could be stated in the mean age of the beginning of lung infection (Staphylococcus = 9.7 years of age - Pseudomonas = 10.1 years of age). Analysing the pulmonary x-ray findings we found a significantly more rapid deterioriation during the follow-up period in patients with permanent Pseudomonas infection than in patients with permanent Staphylococcus infection, whereas the evolution of body height and weight did not take different course.