3H]Ro 19-6327: a reversible ligand and affinity labelling probe for monoamine oxidase-B

This study demonstrated the existence of specific binding sites for [3H]Ro 19-6327 in human platelet membranes. This compound is a novel, time-dependent inhibitor of monoamine oxidase type B (MAO-B) and is structurally closely related to [3H]Ro 16-6491. The density of the sites labelled with high affinity by [3H]Ro 19-6327 was similar to that observed in previous studies with [3H]Ro 16-6491 as ligand. Binding was reversible at 20 degrees C and showed a relatively slow dissociation (t1/2 = 220 min). The dissociation rate was markedly decreased (t1/2 = greater than 24h) at 0 degrees C. MAO-B, but not MAO-A inhibitors, effectively prevented the binding of [3H]Ro 19-6327. Like [3H]Ro 16-6491, [3H]Ro 19-6327 is recognized as a substrate by MAO-B, being eventually deaminated by the enzyme. Since the deaminated aldehyde derivative of Ro 19-6327 did not inhibit MAO-B, a still unidentified reversible adduct, formed at the MAO-B active site, might explain the high potency and selectivity of [3H]Ro 19-6327. Incubation of the radioligand-enzyme complex from platelet and brain membranes with NaBH3CN and acetic acid (to pH 4.5) caused the irreversible incorporation of the radioactivity into a single polypeptide as shown by SDS-PAGE analysis. This polypeptide had a molecular weight identical to that of the MAO-B subunit, i.e. 58,000. The presence of unlabelled MAO-B inhibitors in the incubation mixture prevented the covalent incorporation of [3H]Ro 19-6327. The irreversible MAO-B inhibitor, [3H] pargyline, labelled a protein with a molecular weight identical to the protein labelled by [3H]Ro 19-6327.(ABSTRACT TRUNCATED AT 250 WORDS)     

CT and MRI of the middle ear

Summary High-resolution computed tomography (HRCT) provides excellent contrast between osseous structures, air and soft tissue in conjunction with high spatial resolution. Therefore, thin-section HRCT with bone window setting is the method of choice for the examination of the middle ear structures. The indications are acute and chronic inflammatory changes, cholesteatoma and tumor, the “postoperative middle ear”, and malformations. In most cases, HRCT enables differentiation between inflammatory changes, cholesteatoma, and tumor. The excellent depiction of subtle osseous details enables the identification of erosions of the ossicles or of the bony walls of the mastoid cells, of osseous defects of the tegmen, of the bony labyrinth, and of the tympanic course of the facial canal. In addition, HRCT enables excellent depiction of reconstructions of the ossicles or prosthesis of the ossicles. Although HRCT is the first method of choice, magnetic resonance imaging (MRI) may provide additional information and lead to a more accurate diagnosis in some cases. This is explained by the excellent soft tissue contrast provided by MRI. In addition, MRI offers the possibility of using various pulse sequences and the administration of IV contrast material. Therefore, MRI may allow the differentiation between inflammatory changes, cholesteatoma, and tumor in those cases in which accurate diagnosis cannot be made by HRCT. The differentiation between a meningocele or meningoencephalocele and other entities such as tumors or cholesteatoma can be established by MRI. Furthermore, MRI can accurately depict cases of labyrinthitis or of neuritis of the facial nerve or of intracranial disease caused by middle ear processes, while this is not always possible by HRCT. In summary, HRCT of the middle ear is the method of choice, but MRI may provide supplementary information in those cases in which accurate diagnosis cannot be established by HRCT.      

Precision of three-dimensional CT-assisted model production in the maxillofacial area

Individual skull model fabrication was introduced into preoperative diagnostics in maxillofacial surgery in the mid-1980s. The aim of the present study was to collect information on the reproducibility of a skull model milled from hardened polyurethane foam. This model was based on the CT data of a real skull. Twenty comparative studies were carried out on both the model and the original skull, the model showing an average inaccuracy of 1.6 mm. The deviations ranged between 0.0 and 3.6 mm; the general trend favouring enlargements. The total deviation of the model as compared to the original skull was 1.8%. A convincing aspect of the model, which cannot be obtained by any other method, is its plasticity and the possibility of 3 D orientation on a lifesize model. This new method is already used in preoperative planning of corrections of post-traumatic defects and craniofacial deformities as well as in tumour surgery. Correspondence to: P. Solar     

A new technique for right heart catheterization with a Swan-Ganz balloon catheter via femoral vein in the patient with dilated right heart chambers, utilizing a modified transseptal-type sheath.

Right heart catheterization with a Swan-Ganz balloon catheter via femoral vein in the patient with dilated right atrium and ventricle is frequently difficult due to excessive catheter coiling in the dilated atrium. A new technique is described in this situation. By using a modified transseptal-type sheath positioned counterclockwise in right atrium as an introducing sheath, a balloon catheter can be easily advanced to the distal pulmonary artery by smooth counterclockwise direction and secure support from this sheath.     

Interleukin-7 expression during mouse thymus development.

We have monitored the expression of interleukin-7 (IL-7) in the developing embryonic mouse thymus by a combination of quantitative polymerase chain reaction (PCR) and immunofluorescence microscopy. A strong specific signal for IL-7 mRNA was detected by day 12 in the developing fetal thymus. IL-7 mRNA was found to be maximally expressed on day 15, and then decreased over the next 5 days. Immunofluorescence staining of fetal thymus sections using an anti-IL-7 antibody confirmed these PCR data. IL-7 protein expression was first detected at day 13 of development. At 14 days the intensity of the staining increased by a factor of three and stayed at this level over the next 4 days. The same anti-IL-7 antibody used for immunofluorescence, blocked the proliferation of fetal thymocytes in organotypic cultures. In addition, we detected mRNA coding for IL-2 and SCF (also known as the steel factor or KL) in embryonic thymocytes. The implications of these findings for early thymocyte growth are discussed.     

Method for the quantitative assessment of contrast agent uptake in dynamic contrast-enhanced MRI

In previous papers relative signal intensity increase was used as a quantitative assessment parameter for contrast uptake in contrastenhanced MRI. However, relative signal intensity increase does not only reflect contrast uptake but depends also on tissue parameters (native T₁ relaxation time) and sequence parameters (repetition time and flip angle); thus, the contrast uptake cannot be assessed accurately using relative signal intensity increase. Based on an analysis of the contrast behavior of spoiled gradient echo sequences, a method is described in this paper that overcomes the limitations of relative signal intensity increase measurement. A parameter, called “enhancement factor” (EF) is introduced that approximates differential T₁ relaxation rate. The enhancement factor scales linearly with contrast uptake and is independent of tissue and sequence parameters. The additional measurement time involved in determining the enhancement factor is less than 1 min and computation is straightforward. The practicality of the new method was confirmed by phantom measurements using T₁-weighted and proton density-weighted spoiled gradient echo sequences (FLASH-2D). Enhancing tissues were simulated by water phantoms doped with increasing concentrations of Gd-DTPA.     

Life planning--consequences of a steadily growing life span 1650-2000. Considering the longer life span, do we need a life plan?

Recent social historical studies on the development of life expectancy over the last 300-400 years have shown that the increasing certainty that the great majority of us will be able to live relatively healthy lives until the end is more decisive for most people than the lengthening of the life span itself. A premature death is no longer--as in previous generations--the rule. Today it is the exception. In an historical and worldwide context, we are the first who will--or could--be able to live our lives from the perspective of a relatively calculable, distant end. In order to do this to a greater degree and, above all, more consciously, a "life design" or "life plan" seems to be necessary. This means developing, as early in life as possible, the types of interests that will last a whole life long and will provide fulfillment, particularly in the "Fourth Age". The period of maturity (and waning activity) should not then be one of insufferable emptiness. "Maturity of life" can mean a chance and a goal for most of us today, provided that we structure this life appropriately ourselves. Contributions to discussions in this context in the USA and in two research-related seminars at the Free University of Berlin are presented.     

α6 integrins participate in pro-T cell homing to the thymus

During embryogenesis, colonization of the thymic rudiment by hemopoietic progenitor cells depends on the adhesion of these cells to the jugular endothelium. Previously, we showed that progenitor T cells (pro-T cells) interact with α₆ integrins present on vascular endothelium. Here, we demonstrate that anti-α₆ integrin antibodies reduced the number of thymocytes up to 80 % in a congenic mouse model for thymus colonization by pro-T cells. In organotypic thymus cultures, the anti-α₆ integrin antibodies did not influence T cell development and proliferation. From this, we conclude that α₆ integrin participates in thymus homing. During mouse thymus ontogeny, α₆ integrin mRNA and protein expression was found as early as day 10 of development; at day 11, perithymic endothelial cells were α₆ integrin positive. Two α₆ integrin mRNA exist which are produced by alternative exon usage. The longer form, α₆, integrin, predominates during early embryonic stages, while the shorter α_6A form was present later during development. Although α₆, integrins can be displayed by immature thymocytes, strongest expression was found on intra- and perithymic vascular endothelium. These data suggest that α₆ integrins are involved in the homing of pro-T cells to the developing thymus by mediating adhesion of pro-T cells to the vascular endothelium.