Transgenic mice that express different forms of the influenza virus hemagglutinin as a neo-self-antigen

We have generated transgenic mouse lineages that express the influenza virus hemagglutinin in different physical forms. One kind expresses the full-length hemagglutinin molecule as a cell surface glycoprotein and can be recognized by hemagglutinin-specific B and T cells. The other expresses a truncated polypeptide corresponding to the N-terminal third of the hemagglutinin molecule. This polypeptide encodes known hemagglutinin-specific T-cell determinants; however, it contains no native B-cell epitopes, since these depend on the conformation of the fully folded protein. In each case, the hemagglutinin transgenic mice display ubiquitous expression of transgenic messenger RNA and induce T-cell tolerance to the transgene-encoded T-cell determinant site 1. Thus, the hemagglutinin is a neo-self-antigen in both kinds of hemagglutinin transgenic mice and should provide a useful system for understanding the factors and mechanisms that govern tolerance and autoimmunity to self-antigens.     

Kinesthetic sense of the shoulder in patients with impingement syndrome

A proprioceptive deficit is an important determinant of disability in various shoulder disorders, such as instability and osteoarthrosis. In 15 patients with impingement syndrome stage II (Neer 1983), who were treated by arthroscopic subacromial decompression, we measured movement sense by determining threshold levels for the perception of motion of the shoulder. The patients were placed in a specially designed chair allowing continuous passive motion of the shoulder joint, while avoiding cutaneous, auditory and visual stimuli. To assess movement detection thresholds, passive abduction movements of the shoulder were performed at a starting angle of 60°, an amplitude of 10° and an angular velocity of 1.3°/s. Before surgery, all patients had higher threshold levels for the perception of motion in their affected shoulders then in the other side. After decompression, proprioception had improved on the decompressed side, but was unchanged on the other side.     

Autonomy in the Rehabilitation of Stroke Patients in Nursing Homes. A Concept Analysis

This article presents a concept analysis of autonomy in relation to the rehabilitation of stroke patients. Analysis of the results of a literature survey provided three important concepts of autonomy in the field of biomedical ethics: self-governance, self-realization and actual autonomy. These concepts are compared with concepts from caring sciences and summarized in a table. The results indicate the importance of the social environment (formal and informal caregivers) for the restoration of autonomy. Because of the patient's condition and context, a social concept of autonomy makes more sense in the rehabilitation of stroke patients in nursing homes than does an individual concept. The concept analysis sheds light on the fact that the majority of studies regarding patient autonomy are primarily based on theoretical reflections, not on empirical studies. More research is warranted to gather information on how patients themselves consider and appreciate autonomy during rehabilitation, to explore the views of stroke patients' formal and informal caregivers and to investigate whether a social concept of autonomy is suitable for all phases of rehabilitation. Concerning the practice of rehabilitation, no definite conclusion can be given as yet.     

New Potent Azomethine Prodrugs of the Histamine H3-Receptor Agonist (R)-α-Methylhistamine Containing a Heteroarylphenyl Partial Structure

The therapeutic value of histamine H₃-receptor ligands is under current investigation. On the basis of recently described diaryl imine prodrugs of the histamine H₃-receptor agonist (R)-α-methyl-histamine ( 1 ) a series of new azomethine prodrugs containing five- and six-membered heterocycles were synthesized and tested for their in vitro hydrolysis rates and in vitro activity after oral application. It was found that electron-deficient six-membered heterocycles drastically destabilized the imine double bond so that these prodrugs decomposed unsuitably fast. On the contrary, prodrugs containing five-membered heterocycles appeared to be highly effective for the CNS delivery of 1 , and a remarkable correlation between chemical structure and pharmacokinetic profile was observed. Particularly (R)-4-fluoro-2-[[N-[1-(1H-imidazol-4-yl)-2-propyl]imino](1H-pyrrol-2-yl)methyl]phenol ( 8c ), the 2-furanyl analogue 8d , and its 3-furanyl isomer 8e proved to be equipotent to the most potent of recently described halogenated diaryl imine prodrugs of 1. However, in contrast to any other azomethine prodrug, 8c exhibited an incomparably long lasting delivery of 1 in the CNS and can thus be regarded as a ‘retard’ prodrug. Assuming that a therapeutic indication of histamine H₃-receptor agonists will soon be established, these highly potent heteroarylphenyl azomethine prodrugs, which already serve as valuable pharmacological tools, may also become potential drugs in clinical use.