Modulation of the allergic immune response in BALB/c mice by subcutaneous injection of high doses of the dominant T cell epitope from the major birch pollen allergen Bet v 1

Several in vitro and in vivo studies indicate that application of high doses of dominant T cell epitopes can induce a state of antigen-specific non-responsiveness (anergy). In the present study, we developed a murine model of an allergic immune response to Bet v 1, the major birch pollen allergen. Mice were sensitized by injection of rBet v 1 and the allergic state was proven by the presence of allergen-specific IgE and positive immediate-type skin tests to Bet v 1. In epitope mapping experiments, an immunodominant T cell epitope of Bet v 1 in BALB/c mice was identified by the use of overlapping peptides. This peptide (BV 139) was subsequently employed for treatment. Two tolerization protocols were used: in one approach, the peptide was administered to naive mice before immunization (group BV139-S), in the second, already sensitized mice were treated (S-BV139). The results demonstrated that administering high doses of the dominant T cell epitope of Bet v 1 profoundly diminished T cell proliferation to the peptide in the BV139-S group, and to the peptide as well as to the whole protein in the S-BV139 group. Skin test reactivity to Bet v 1 was reduced in the BV139-S group. However, no differences in terms of specific antibody production between treated and untreated mice could be observed. This study provides evidence that administration of dominant T cell epitopes can down-regulate the allergen-specific T cell response. Proceeding on the assumption that the T lymphocyte response to allergens is crucial for the induction and maintenance of the allergic disease, a modulation of the immune response to allergens by treatment with T cell epitope peptides could represent a promising concept for immunotherapy in the future.     

Formal program construction by transformations-computer-aided,intuition-guided programming

Formal program construction by transformations is a method of software development in which a program is derived from a formal problem specification by manageable, controlled transformation steps which guarantee that the final product meets the initial specification. This methodology has been investigated in the Munich project CIP (computer-aided intuition-guided programming). The research includes the design of a wide-spectrum language specifically tailored to the needs of transformational programming, the construction of a transformation system to support the methodology, and the study of transformation rules and other methodological issues. Particular emphasis has been laid on developing a sound theoretical basis for the overall approach     

Identification of spherical virus particles in digitized images of entire electron micrographs

Interferon-gamma (IFN-gamma) has the most potent immunomodulatory activity of all the interferons. This phase II-B study was performed to define time- and dose-dependent immunomodulatory effects mediated by IFN-gamma in a subset of patients with melanoma treated in the dose-seeking therapeutic trial conducted by the Eastern Cooperative Oncology Group E4687 (13). The effects of IFN-gamma (Genentech, San Francisco, CA) were evaluated for phenotype and function of peripheral blood lymphocytes obtained twice prestudy, and on days 2, 9, and 29 of IFN-gamma therapy for 50 patients. Early significant increases in CD4/CD8 ratio (p = 0.001) were noted, largely due to a rise in CD4+ and fall in CD8+ T-cell populations sustained through day 29 at only the lowest dosage. Increased natural killer cell (NK) activity (p = 0.001 on day 9; p = 0.01 on day 29) was accompanied by durable increases in circulating activated NK cells (CD56+DR+% p = 0.001, day 9; p = 0.001, day 29). After initial depression of CD56+ and CD16+ cells on day 2, the total percent of CD56+ and CD16+ cells increased significantly by day 29. Increases in NK cell activity were maximal at doses > or =0.1 mg. Monocyte CD14+ expression of DQ+ rose early (p = 0.011 and 0.001 on days 2 and 9), accompanied by elevation in CD14+DR+ cells that was less significant. Immunomodulatory effects of IFN-gamma reported in this trial have major implications for interpretation of past and current clinical trials, and the design of future trials. This is the first trial in which IFN-gamma has been shown to have significant effects on the T-cell compartment of the immune system.     

Induced free liquid surface oscillations in a visco-elastic liquid column due to angular temperature fluctuations

The response due to time-fluctuating temperature distribution applied at the free surface of a viscoelastic cylindrical liquid column with no axial dependency has been determined analytically. The amplitude of the radial- and angular velocity as well as the free liquid surface elevation has been presented as a function of the “reduced” forcing frequency of the oscillatory temperature and has numerically been evaluated for an angular temperature field proportional to sin 2φ. It was found, that visco-elasticity as described by the Maxwell model has quite some influence upon the liquid behavior. It shows for larger relaxation times besides the enlarged resonance peak additional peaks below and above resonance. This is particularly evident inside the liquid column, indicating a more pronounced elastic behavior of the liquid.     

Improvement of the engineering properties of asphalt pavements using a ‘soft’ compaction technique (AMIR-Compaction)

In most countries of the world asphalt pavement of road networks represents the biggest single investment in the transportation system. In Canada, asphalt pavement built over the past decade is worth more than 70 billion dollars (in 1984 dollars). In order to maintain the current road network at the present level of service and prevent it from further deterioration, over 6 billion dollars is needed anually.

Traditionally, asphalt overlays are widely used to rehabilitate existing deteriorated pavements. Unfortunately the new overlays have been observed to fail in a relatively short time. Thus the investment in overlays is lost.

Recent research based on the concept of relative rigidity has indicated that the rapid deterioration of new asphalt overlays is directly related to current construction equipment. It has been shown analytically and experimentally that steel rollers used in compacting the asphalt layer will result in surface cracks during construction. Traffic and environmental influences will accelerate the failure of the new layer.

This paper presents the results of a testing programme evaluating the engineering properties of asphalt slabs compacted by a new method using a compactor termed AMIR. The results showed that the AMIR compactor will prevent the formation of constitution cracks resulting in an increase of indirect tensile strength of 10% and an increase of direct tensile strength of up to 60% when compared to steel roller compacted asphalt slabs.     

Use of solid phase extraction disks for the GC-MS analysis of acidic and neutral herbicides in drinking water

An analytical procedure was developed in which thirteen herbicides (10 acidic and 3 neutral compounds) may be extracted from drinking water samples using solid phase extraction disks and subsequently analyzed by gas chromatography-mass spectrometry. Using 8 replicate samples consisting of reagent water fortified with nanogram quantities of each herbicide, the average percent recoveries and method detection limits were determined for each analyte. The method was found to be suitable for the determination of individual herbicides in drinking water at concentrations of approximately 10 ng/L.     

Clinical significance of sleep apnea disorders after implantation of a cardioverter-defibrillator in patients with cardiac disease and sustained ventricular tachyarrhythmia

The purpose of our study was to determine the prevalence of sleep related breathing disorders (SRBD) in patients with an implantable cardioverter-defibrillator (ICD) and to evaluate prospectively the possible influence of SRBD on arrhythmia recurrence and circadian arrhythmia variation as well as on cardiac mortality during long-term follow-up. Forty consecutive ICD recipients with cardiac disease and a documented history of spontaneous, life-threatening, ventricular tachyarrhythmias underwent full-night polysomnography and were followed for 2 years. In 16 of 40 patients (40%), SRBD were diagnosed (Apnea/Hypopnea Index (AHI) > 10); in 9 of these 16 patients (56%) central sleep apneas (CSA) occurred (in 8 of these 9 patients in combination with Cheyne-Stokes respiration). Seven of the 16 patients with SRBD (44%) revealed obstructive sleep apneas (OSA). AHI was 32 +/- 15 (12-60) in patients with CSA and 32 +/- 27 (11-86) in patients with OSA. Patients with and without SRBD were comparable concerning left ventricular ejection fraction, NYHA classification, cardiac disease, ICD indication, and concomitant medication. ICD registered ventricular tachyarrhythmias occurred in 10 of 24 patients (42%) without SRBD, in 4 of 9 patients (44%) with CSA, and in 3 of 7 patients (44%) with OSA. The numbers and circadian variation of episodes registered during follow-up in patients without SRBD, with OSA or CSA were comparable (14 +/- 25, median 4 vs 15 +/- 15, median 7 vs 4 +/- 5, median 2.5). The 2-year cardiac mortality was highest in patients with CSA (4/9 (44%) vs. 0/7 patients (0%) with OSA vs 3/24 patients (12.5%) without SRBD. Thus, the prevalence of SRBD in patients with chronic heart failure and a history of malignant ventricular tachyarrhythmias is high (40%) and the occurrence of CSA seems to be predictive for cardiac mortality in these patients. An influence of moderate SRBD on arrhythmia recurrence and circadian variation of spontaneous sustained tachyarrhythmic events could not be demonstrated.