Mathematische Behandlung der Überlebenskurve von Mäusen nach einmaliger kurzzeitiger Ganzkörperbestrahlung

Zusammenfassung Es wird eine, unter einigen vereinfachenden Annahmen aufgestellte Formel angegeben, die den Zusammenhang zwischen Strahlendosis und der mittleren Überlebenszeit bei einmaliger kurzzeitiger Ganzkörperbestrahlung von Mäusen (Rajewsky) annähernd beschreibt. Die Formel wird aus einer Modellvorstellung abgeleitet, nach der der Tod des Tieres durch das strahlenbiologische Verhalten von drei verschiedenen Zellsystemen determiniert ist. Auch die Resultate bei Dauerbestrahlungen von Mäusen mit Dosisleistungen zwischen 0,46 und 805 kR/Tag (Rajewsky et al.) werden durch die Formel näherungsweise wiedergegeben.

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Summary A formula is given which describes the relation doseva mean survival time after single whole-body irradiation of mice (Rajewsky). The formula is derived from a model explaining the death of the animal as result of the radiation reaction of three different cellular systems. The formula gives account too for the results of continuous irradiations of mice with dose rates between 0,46 and 805 kR/day (Rajewsky et al.).

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Im Auszug vorgetragen auf dem 11. Internationalen Kongress für Radiologie in Rom (22.–28. 9. 65).     

Effects of inhaled corticosteroids on sputum cell counts in stable chronic obstructive pulmonary disease: a systematic review and a meta-analysis

Background

Whether inhaled corticosteroids suppress airway inflammation in chronic obstructive pulmonary disease (COPD) remains controversial. We sought to determine the effects of inhaled corticosteroids on sputum indices of inflammation in stable COPD.

Methods

We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Databases for randomized, controlled clinical trials that used induced sputum to evaluate the effect of inhaled corticosteroids in stable COPD. For each chosen study, we calculated the mean differences in the concentrations of sputum cells before and after treatment in both intervention and control groups. These values were then converted into standardized mean differences to accommodate the differences in patient selection, clinical treatment, and biochemical procedures that were employed across original studies. If significant heterogeneity was present (p < 0.10), then a random effects model was used to pool the original data. In the absence of significant heterogeneity, a fixed effects model was used.

Results

We identified six original studies that met the inclusion criteria (N = 162 participants). In studies with higher cumulative dose (≥ 60 mg) or longer duration of therapy (≥ 6 weeks), inhaled corticosteroids were uniformly effective in reducing the total cell, neutrophil, and lymphocyte counts. In contrast, studies with lower cumulative dose (< 60 mg) or shorter duration of therapy (< 6 weeks) did not demonstrate a favorable effect of inhaled corticosteroids on these sputum indices.

Conclusions

Our study suggests that prolonged therapy with inhaled corticosteroids is effective in reducing airway inflammation in stable COPD.     

Immunoproteasome responds to injury in the retina and brain

It is well known that immunoproteasome generates peptides for MHC Class I occupancy and recognition by cytotoxic T lymphocytes (CTL). The present study focused on evidence for alternative roles for immunoproteasome. Retina and brain were analyzed for expression of immunoproteasome subunits using immunohistochemistry and western blotting under normal conditions and after injury/stress induced by CTL attack on glia (brain) or neurons (retina). Normal retina expressed substantial levels of immunoproteasome in glia, neurons, and retinal pigment epithelium. The basal level of immunoproteasome in retina was two-fold higher than in brain; CTL-induced retinal injury further up-regulated immunoproteasome expression. Immunoproteasome up-regulation was also observed in injured brain and corresponded with expression in Purkinje cells, microglia, astrocytes, and oligodendrocytes. These results suggest that the normal environment of the retina is sufficiently challenging to require on-going expression of immunoproteasome. Further, immunoproteasome up-regulation with retinal and brain injury implies a role in neuronal protection and/or repair of damage.     

Crystallization of cowpea chlorotic mottle virus

Cowpea chlorotic mottle virus belongs to the brome mosaic virus group of the small spherical plant viruses. It contains 180 protein subunits, which are arranged on a T = 3 icosahedral surface lattice. The virus crystallizes in orthorhombic space group P2₁2₁2 ($\text{a = 394}\text{A}\text{?}\text{, b = 382}\text{A}\text{?}\text{,}\text{and}\text{c = 397}\text{A}\text{?}$). The unit cell contains four virus particles, while the crystallographic asymmetric unit consists of one complete virion. X-ray diffraction data from the crystals extend to nearly 3.0 Å resolution.     

Floral scent and its correlation with AFLP data in Sorbus

Comparisons between floral scent-based and DNA-molecular-based taxonomies are rare, yet such comparisons indicate that scent can provide useful taxonomic information. Here, we correlate the phytochemical differentiation in floral scent to the DNA-molecular-based differentiation in the genus Sorbus. Inflorescence scent patterns of the apomictic and endemic Sorbus latifolia microspecies Sorbus franconica, Sorbus adeana, and Sorbus cordigastensis originated by hybridization as well as their parental taxa Sorbus aria agg. and Sorbus torminalis were investigated with the dynamic headspace method. The scent data (presence/absence of compounds) were used to construct an UPGMA tree, to calculate a similarity matrix, and to correlate them with the published amplified fragment length polymorphism (AFLP) data of the same individuals, populations, and taxa. Flow cytometry was used to estimate the DNA-ploidy level of the taxa. Scent analyses showed a total of 68 substances, among them aromatic compounds, terpenoids, aliphatics, and nitrogen-containing compounds. The scent patterns were taxon-specific, and the number of scent components differed among taxa. The correlations with the published AFLP data on population and individual level are highly significant, indicating that the scent and AFLP data are highly congruent in the plants studied. Scent therefore provides useful taxonomic characters in Sorbus.     

Weitere Untersuchungen zur strahlenbedingten Lebensverkürzung bei Versuchstieren nach Dauerbestrahlung

Zusammenfassung Es wird über verschiedene Dauerbestrahlungsversuche mit Röntgenstrahlen an Mäusen mit Dosisleistungen zwischen 0,8 und 750 R/Tag berichtet. Aus den Ergebnissen werden u. a. die folgenden Schlüsse gezogen: Es ist eine strenge begriffliche Trennung zwischen der Spätschädigung und den akuten Effekten notwendig. Die Kenntnis der Altersabhängigkeit der Lebensverkürzung nach einmaliger Bestrahlung mit kleinen Strahlendosen erlaubt es, Schlüsse auf die Lebensverkürzung bei Dauerbestrahlungen zu ziehen. Bei einer Dauerbestrahlung wird der Effekt im wesentlichen durch die im ersten Lebensdrittel empfangenen Dosis bestimmt. Die unterschiedliche RBW von Röntgenstrahlen gegenüber Gammastrahlen wurde in einem Dauerbestrahlungsversuch mit 50 R/Tag erneut bestätigt. Bei Dauerbestrahlungen von Mäusen mit Röntgenstrahlen und Dosisleistungen oberhalb von 25 R/Tag wird der Tod der Tiere durch die gleichen Schädigungen verursacht, die nach einmalig-kurzzeitiger Bestrahlung als akutes Strahlensyndrom auftreten. Es wird ein Modell angegeben, welches den Zusammenhang zwischen Lebensverkürzung und Dosisleistung bei Dauerbestrahlungen beschreibt. Bei Mäusen ergab sich bei einer Bestrahlung der vorderen bzw. der hinteren Körperhälfte mit 2×300 R in beiden Fällen die gleiche Lebensverkürzung.

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Life-shortening of mice after long term irradiation with X-rays

Summary Results of long term irradiations of mice with X-rays (dose rates 0.8 to 750 R/ day) were reported. Life shortening in these experiments may be calculated from results of age dependency of life shortening after single short irradiations with low doses. In long term irradiations life shortening is caused mainly by the dose received during the iuvenile period. A model is proposed, which relates life shortening in long term irradiations with dose rate. Irradiation of the upper or the lower part of the body of a mouse with 2×300 R results in the same life shortening.

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Herrn Professor Dr. B.Rajewsky zum 75. Geburtstag gewidmet.

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Für die unermüdliche Hilfe bei der Durchführung der Versuche habe ich Frl. G.Jureeit, Frl. E.Midunsky und Herrn G.Manthey herzlich zu danken.     

Significance of nucleotide sequence alignments: a method for random sequence permutation that preserves dinucleotide and codon usage

The similarity of two nucleotide sequences is often expressed in terms of evolutionary distance, a measure of the amount of change needed to transform one sequence into the other. Given two sequences with a small distance between them, can their similarity be explained by their base composition alone? The nucleotide order of these sequences contributes to their similarity if the distance is much smaller than their average permutation distance, which is obtained by calculating the distances for many random permutations of these sequences. To determine whether their similarity can be explained by their dinucleotide and codon usage, random sequences must be chosen from the set of permuted sequences that preserve dinucleotide and codon usage. The problem of choosing random dinucleotide and codon-preserving permutations can be expressed in the language of graph theory as the problem of generating random Eulerian walks on a directed multigraph. An efficient algorithm for generating such walks is described. This algorithm can be used to choose random sequence permutations that preserve (1) dinucleotide usage, (2) dinucleotide and trinucleotide usage, or (3) dinucleotide and codon usage. For example, the similarity of two 60-nucleotide DNA segments from the human beta-1 interferon gene (nucleotides 196-255 and 499-558) is not just the result of their nonrandom dinucleotide and codon usage.