Regulatory T cells and antigen-specific tolerance.

Foxp3-expressing regulatory T cells (Tregs) have an essential function of preventing autoimmune disease in man and mouse. Foxp3 binds to forkhead motifs of about 1,100 genes and the strength of binding increases upon PMA/ionomycin stimulation. In Foxp3-expressing T-cell hybridomas, Foxp3 promoter binding does not lead to activation or suppression of genes which becomes only visible after T-cell activation. These findings are in line with observations by others that Foxp3 exerts important functions through association with Tcell receptor (TCR)-dependent transcription factors in a DNAbinding complex. Tregs can be generated when developing T cells encounter TCR agonist ligands in the thymus. This pro - cess requires costimulatory signals. In contrast, extra thymic conversion of naive T cells into Tregs is inhibited by costimulation. In fact, DC-derived retinoic acid (RA) helps the conversion process by counteracting the negative impact of costimulation. Since AP-1 is produced after costimulation and appears to interfere with Foxp3-NFAT transcription complexes, it is of interest to note that RA interferes with AP-1-dependent transcription. Thus, RA may interfere with the negative impact of costimulation on Treg conversion by interfering with the generation and/or function of AP-1.

Pancreatic NOD beta cells express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes.

AIMS/HYPOTHESIS: In the NOD mouse model, attempts to show MHC class II expression by pancreatic beta cells were unsuccessful so far. We readdressed this question by analysing I-A(g7) expression in single pancreatic beta cells. METHODS: Single-cell multiplex RT PCR and single-cell immunofluorescence were used to study MHC class II expression in NOD and NOD/SCID beta cells. RESULTS: Pancreatic beta cells from NOD mice express the I-A(g7) protein as well as the corresponding mRNA. The frequency of MHC class II mRNA-expressing beta cells is drastically increased during the progression to overt diabetes. MHC class II protein is accumulated intracellularly, and invariant chain is co-expressed. Beta cells from 9- to 10-week-old NOD/SCID mice express MHC class II at the same low frequency as beta cells from 3-week-old NOD mice. CONCLUSION/INTERPRETATION: NOD beta cells express I-A(g7) and could be a direct target of autoreactive CD4+ T cells. This MHC class II expression is triggered by infiltrating lymphocytes.

[Radiologic diagnosis of abdominal trauma]. / Radiologische Diagnostik des abdominellen Traumas.

In Europe ultrasonography has displaced diagnostic peritoneal lavage (DPL) in the primary survey of polytraumatized patients with suspected abdominal trauma. Hemodynamically unstable patients who are brought to the emergency room with blunt abdominal trauma will go directly to the operating room after a rapid ultrasonography examination with evidence of hemoperitoneum. In hemodynamically stable patients, in addition to ultrasonography, computed tomography can be done. This is especially efficient if evaluation with sonography is not completely possible or shows little pathology (e.g. small amounts of hemoperitoneum).

[MR tomography (MRT) of the skeleton, peripheral soft tissues and joints--current overview]. / MR-Tomographie (MRT) des Skeletts, der peripheren Weichteile und der Gelenke--Aktuelle Ubersicht.

A review: The skeleton, the peripheral soft tissues, and the joints have become important indications to use MRI routinely. About 25-35% of daily examinations focus on these anatomic sites. Superior contrast resolution, the option of different imaging planes, and the unsurpassed visualization of bone marrow, fibrous and hyaline cartilage, ligaments, and tendons are the reasons for the overwhelming success of this imaging method. MRI often provides the direct way to diagnosis. More and more the so-called "step by step" approach to diagnosis by imaging methods is being abandoned in favor of the primary use of MRI. The present survey summarizes the main indications for MRI in the field of the musculoskeletal system, in adults as well as in children. Special topics like tumors, inflammation, ischemia, and trauma are discussed. Some anatomic sites like the carpal joint, the shoulder, and the knee are presented in more detail.

[Treatment of stenosed or occluded hemodialysis shunts. Results of percutaneous angioplasty and combined radiologic-surgical therapy]. / Rekanalisation von stenosierten oder verschlossenen Hämodialyseshunts. Ergebnisse der perkutanen Angioplastie und der kombiniert radiologisch-chirurgischen Therapie.

The results of all recanalisations of stenosed and occluded haemodialysis shunts over a period of three years are reported; there were 112 percutaneous angioplasties and 40 combined radiological-surgical procedures. In 13% of cases a metallic endoprosthesis (wall stent) and in 3% Simpson's atherectomy catheter was used. The functional results were retrospectively evaluated for all 152 interventions which involved 60 orthoptic Brescia-Cimino shunts and 19 PTFE prostheses. In addition, the primary and total functions of the treated shunts were calculated. Cumulative function rate (percentage at a given time of effective shunts) for Brescia-Cimino shunts at one year was 80% and after two years 68.5%; for the PTFE prosthesis the corresponding figures were 83.8 and 75.5% respectively. The average number of interventions per patient was 2.3 with a range of 1-7. Total functional rate of all shunts following the first percutaneous procedure after one year was 78.2%, for combined radiological-surgical procedures for the treatment of acute thromboses it was 68%. Comparison with the results of surgical treatment reported in the literature confirms the effectiveness of percutaneous or combined treatment of stenosed or acutely occluded haemodialysis shunts. The outstanding advantage of radiological intervention is its repeatability.

[Interactions of detergents with phospholipid bilayers at sublytic concentrations--partition or binding?]. / Wechselwirkung von Detergenzien mit Phospholipid-Doppelschichten im sublytischen Bereich--Verteilung oder Bindung?

Using the bubble pressure method the interaction of liposomes with detergents at sublytic concentrations was studied. The results are discussed in terms of a partition or binding model. The findings support an equilibrium partition of the surfactant between the aquous and lipid phase. For some detergents, however, concentration dependent partition coefficients were found.

[Temperature dependence of membrane-bound aldehyde dehydrogenase from Acinetobacter: effect of solubilization and chain length of the substrates]. / Temperaturabhängigkeit der membrangebundenen Aldehyddehydrogenase aus Acinetobacter: Einfluss der Solubilisierung und der Kettenlänge der Substrate.

The NADP+-dependent aldehyde dehydrogenase of intracytoplasmic membranes of Acinetobacter calcoaceticus shows a characteristic behaviour of its reaction velocities in dependence on temperature. The calculated "real" activation energies depend on the increasing chain-length of the homologous aldehydes and grow appropriate to the membrane-bound and to the micellar form of the enzyme with 6.2 and 7.3 kJ/mole CH2-group, respectively. The values of the activation energy of the membrane-bound enzyme are - for each aldehyde of the homologous series - 12 kJ/mole larger than those of the solubilized enzyme (present as mixed micelles of enzyme, cholate and bacterial phospholipids).

A method to measure critical detergent parameters. Preparation of liposomes.

A simple physical method to determine the monomer concentration of detergents below as well as above the critical micelle concentration based on the bubble-pressure measurement is described. Aggregated surfactant molecules (micelles) and phospholipid vesicles if present in the sample will not disturb the measurements. Three applications of the method relevant to the preparation of liposomes are shown: (i) measurements of critical micelle concentrations, (ii) evaluation of the affinity constant of the interaction of detergents with liposomal membranes, and (iii) monitoring of residual detergent in liposome preparations during dialysis or after gel chromatography of mixed micelle-derived liposomes. It was found that the efficiency of detergents to produce liposomes during their removal depends on their critical micelle concentrations as well as on their affinity to liposomal membranes.

Auto-oxidation-induced fusion of lipid vesicles.

Spontaneous size changes of small unilamellar vesicles with initial mean diameters of 25 nm measured by quasi-elastic light scattering (QELS) and electron microscopy are reported. After the size conversion the vesicles have mean diameters of about 70 nm and are of the unilamellar and multilamellar type. The fact that auto-oxidation initiates this process is established by the comparison of the results for vesicles which differ only in the degree of auto-oxidation. The role of phosphatidylcholine hydroperoxides as fusogens is discussed.

[Longitudinal rupture of the aortic arche (author's transl)]. / Aortenbogenlängsruptur.

This is a case report of a 75 year old man who sustained a longitudinal rupture of the aortic arch in addition to cerebral and extremity trauma following a traffic accident. An emergency operation without the use of the heart-lung-machine could not save the patient's life. Possible mechanisms leading to this unusual damage to the aortic arch are discussed.