Evidence that defective interferon-gamma production in atopic dermatitis patients is due to intrinsic abnormalities.

The in vitro production of interferon-gamma (IFN-gamma) in 19 atopic dermatitis (AD) patients was compared with that of 12 controls. IFN-gamma production by phytohaemagglutinin (PHA) stimulated peripheral blood mononuclear cells (PBMC) was profoundly diminished in AD patients, whereas the proliferative response was similar to that of control PBMC. The addition of 40 U/ml of interleukin-2 (IL-2) to the cultures failed to restore IFN-gamma production. Similarly, removal of adherent cells also had no effect. Reduced IFN-gamma secretion was observed after stimulation with the CD3 monoclonal antibody OKT3, ionomycin + 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or with high levels of IL-2 (200 U/ml). There were increased proportions of CD4+ T helper/inducer cells and decreased proportions of CD8+ T cytotoxic-/suppressor cells and CD16+ natural killer (NK) cells in AD patients. This resulted in an increased CD4/CD8 ratio as compared with controls, but no correlation was observed between numbers of T cell subpopulations and IFN-gamma generation. However, a significant correlation was found between IFN-gamma generation in vitro and IgE serum concentration in AD patients. The data suggest that the decreased production of IFN-gamma by AD patients is due to intrinsic differences in capacity to produce this cytokine and is not the result of differences in regulatory cell interactions. Moreover, the findings indicate that decreased production of IFN-gamma may be an important factor in the pathogenesis of this disease.     

Untersuchungen über die spezifische und quantitative Erfassung des Liquor-γ-Globulins mit der Zinksulfatfällung

Zusammenfassung Die Frage der quantitativen und elektiven Erfassung des Liquor--Globulins mit der vonRoboz u. Mitarb. beschriebenen Zinksulfatfällung wurde an Modellversuchen mit reinem -Globulin und Albumin und an der elektrophoretischen Auftrennung des mit Zinksulfat aus Liquor präzipitierten Proteins untersucht. Aus reinen -Globulinlösungen wurden in Abhängigkeit zu der in Ansatz gebrachten -Globulinmenge nur 18–46% gefällt. Das Elektrophoresediagramm der mit Zinksulfat gefällten Liquorproteine zeigte, daß neben einer Anreicherung des -Globulins eine Fällung sämtlicher Liquorproteine zustande kam. Die elektrophoretische Auftrennung der im Überstand der Fällung verbliebenen Eiweißkörper ließ neben den übrigen Fraktionen noch eine deutliche -Globulinbande erkennen. Eine elektive und quantitative Fällung des Liquor--Globulins mit der Zinksulfatmethode konnte demnach nicht nachgewiesen werden.Herrn Dozent Dr.H. Bauer danke ich für die Anregung und Unterstützung bei Durchführung dieser Untersuchungen.     

Light-activated ion channels for remote control of neuronal firing

Neurons have ion channels that are directly gated by voltage, ligands and temperature but not by light. Using structure-based design, we have developed a new chemical gate that confers light sensitivity to an ion channel. The gate includes a functional group for selective conjugation to an engineered K(+) channel, a pore blocker and a photoisomerizable azobenzene. Long-wavelength light drives the azobenzene moiety into its extended trans configuration, allowing the blocker to reach the pore. Short-wavelength light generates the shorter cis configuration, retracting the blocker and allowing conduction. Exogenous expression of these channels in rat hippocampal neurons, followed by chemical modification with the photoswitchable gate, enables different wavelengths of light to switch action potential firing on and off. These synthetic photoisomerizable azobenzene-regulated K(+) (SPARK) channels allow rapid, precise and reversible control over neuronal firing, with potential applications for dissecting neural circuits and controlling activity downstream from sites of neural damage or degeneration.     

Alternating copolymerization of butadiene and propene with the catalyst VO(ONeo)2 Cl/Al(i-C4H9)3, 1

The influence of basic reaction parameters—the ratio of catalyst components, the composition of the monomer mixture and the temperature—on the progress of the copolymerization, the molecular weight and the molecular weight distribution as well as on the composition of the copolymers obtained is reported. Conversion data for the variation of the mole ratio of comonomers show a maximum for an [Al]/[V] mole ratio of approximately 7, whereas the molecular weight of copolymers is not significantly influenced. An increase in the molecular weight of the copolymers can be obtained by an increase of butadiene content in the monomer mixture. However, there is also an increasing incorporation of butadiene into the copolymer. Raising the temperature from ?60°C to 0°C results in a significant decrease in molecular weight, whereas the composition of the copolymers is not significantly changed.     

Separate and variably shaped chromosome arm domains are disclosed by chromosome arm painting in human cell nuclei

Fluorescence in situ hybridization (FISH) with microdissection probes from human chromosomes 3 and 6 was applied to visualize arm and subregional band domains in human amniotic fluid cell nuclei. Confocal laser scanning microscopy and quantitative three-dimensional image analysis showed a pronounced variability of p- and q-arm domain arrangements and shapes. Apparent intermingling of neighbouring arm domains was limited to the domain surface. Three-dimensional distance measurements with pter and qter probes supported a high variability of chromosome territory folding.     

Expression of cathepsin K in lung epithelial cells

Alveolar and bronchial epithelial cells have been shown to have regulatory functions in the maintenance of lung structure and function. Recent evidence supports the premise that these cells can synthesize a variety of extracellular matrix components in vitro, suggesting an active participation in connective tissue remodeling. Their possible role in extracellular matrix degradation, however, is less clear. This study addresses the question of whether alveolar and bronchial epithelial cells express the highly collagenolytic and elastinolytic cysteine proteinase cathepsin K, which has recently been newly described. We provide evidence that the epithelial cell lines A549 and BEAS-2B are capable of expressing cathepsin K messenger RNA. Furthermore, we show that cathepsin K is expressed in normal bronchial epithelial cells. Western blot analyses of human lung-tissue lysates revealed specific immunoreactivity at molecular weights of 46 and 27 kD, corresponding to the procathepsin and the mature cathepsin K. Immunohistochemical analyses showed a pronounced staining of bronchial epithelial cells and in single alveolar epithelial cells. Using a specific fluorogenic cytochemical assay, the intracellular activity of the enzyme was localized. These findings demonstrate that bronchial and alveolar epithelial cells are capable of expressing cathepsin K, which could be of considerable importance for remodeling processes of the extracellular matrix in the lung.     

Aerobic power and pubertal peak height velocity in Belgian boys

Summary To determine the cardiorespiratory response to maximal exercise before, during and after the pubescent growth spurt, thirty boys were tested at yearly intervals over a period of six consecutive years. For each individual, peak height velocity (PHV) was determined. The age at PHV (¯X= 13.6 years) was taken as a standard of maturation. The results from all subjects at 1.5 and 0.5 years before and 0.5 and 1.5 years after PHV are presented. The highest oxygen uptake ( ) obtained during an incremental bicycle ergometer test to voluntary exhaustion was taken as peak oxygen uptake ( peak). Across each of the four years studied, mean peak (min=49.6; max=52.5 ml·kg^–1·min^–1) and mean heart rate (HR) at peak (min=190; max=192) did not change significantly as a function of PHV. On the other hand, the respiratory quotient at peak increased considerably from mean minima and maxima of 0.99 and 1.01 before PHV to 1.07 and 1.10 after PHV. Ventilatory equivalent for ( ), taken as an indicator of ventilatory economy, seemed to be unaffected by the maturation process. The steepest increase in circumpubertal oxygen pulse was found one year after PHV. Average stability coefficients (¯r), calculated from the inter-years correlations were high for height (¯r=0.95), weight (¯r=0.92), HR at peak (¯r=0.74), peak in 1/min (¯r=0.71), oxygen pulse (¯r=0.68) and tidal volume (¯r=0.64).     

The time course of glycogen depletion in single fibers of chronically stimulated rabbit fast-twitch muscle

A time course study was conducted to investigate the possibility of a relationship between fiber degeneration and glycogen depletion in chronically nerve-stimulated extensor digitorum longus muscle of the rabbit. Muscles were stimulated 12 h daily at 10 Hz using alternating one-hour periods of stimulation and rest. When measured for the first time after 3 h (1 h stimulation, 1 h rest, 1 h stimulation), microphotometry revealed complete glycogen depletion of all fiber types (fast glycolytic, FG; fast oxidative glycolytic, FOG; slow oxidative, SO). Different responses were noted beginning at day 4. At this time point, all FOG and SO fibers recovered their glycogen stores with some of the FOG population attaining levels higher than the FOG fibers in the unstimulated, contralateral muscle. Approximately 28% of the FG fibers recovered to normal glycogen values, whereas 58% remained depleted and 14% displayed overshoting glycogen levels. Fifteen percent of all fibers were glycogen-depleted after 12 days of stimulation. At this time, classic fiber types could no longer be distinguished. Fiber degeneration, which was recognized by the invasion of nonmuscle cells, began after 6 days and was restricted to the glycogen-depleted fibers. By this time, there was also a significant increase in DNA content. Exhaustions of glycogen, the main fuel of the FG fibers, is believed to cause a collapse of energy-supply and ATP-driven ionic pumps. The latter could be the initial step of fiber deterioration.