Evidence for neuronal apoptosis in pontosubicular neuron necrosis

Pontosubicular neuron necrosis (PSN) is characterized by acute neuronal death in the subiculum and the pons occurring in a circumscribed perinatal period. The morphological changes in PSN are quite similar to those described during apoptosis, a form of programmed cell death. Morphological re-evaluation of the lesions by light and electron microscopy revealed the typical changes of apoptosis with condensed basophilic nuclei and the formation of apoptotic bodies. By analysing DNA fragmentation in situ with a recently established technique, we were able to show that neuronal death in PSN is apoptotic. The demonstration of DNA fragmentation by the in situ tailing technique was reliable in the human autopsy material used in this study and was only slightly affected by autolysis or formalin fixation. The subiculum and the pons are shown to be susceptible to apoptosis at different times during development. PSN thus provides a model in which the process of nerve cell apoptosis in the developing human central nervous system can be studied.     

Muskelspindeln und sensible Endkörper in Harnröhrenschließmuskel

Summary Neurohistological investigations of the external urethral sphincter in a 2-day-old female baby proved the up till now not verified existence of muscle spindles. These are rare in number, in the majority containing only one intrafusal fiber. Beside of the spindles encapsulated nerve endings, situated in the interstitial tissue and marginal parts of the muscle fascicles, were detected.

     

NK cells and the nervous system

Light- and electron-microscopic studies of human, mouse, rat and guinea pig tissue subjected to PAP and ABC immune reactions revealed, that a monoclonal antibody against human natural killer cells (LEU 7) reacted also specifically with neural elements. In man, not only NK cells, but also myelin sheaths, oligodendrocytes, neurones, astroglial and ependymal cells as well as some enterochromaffin cells were labelled. Similar results, with the exception of negative ependymal cells, were obtained in the laboratory animals investigated. Controls and experiments using another monoclonal antibody against human natural killer cells (VEP 13) were negative. The presence of an antigen shared by human natural killer cells and neural elements could be of importance for the pathogenesis of demyelinating disorders.     

Histogenesis of demyelinating lesions in the spinal cord of guinea pigs with chronic relapsing experimental allergic encephalomyelitis

Spinal cord lesions in Hartley guinea pigs with chronic relapsing experimental allergic encephalomyelitis (EAE) were studied by light, transmission and scanning electron microscopy at different stages of the formation of demyelinated plaques. In addition the inflammatory response in the meninges was studied in isolated pia mater preparations separated from the spinal cord surface. In initial chronic lesions in the spinal cord, inflammation was restricted to penetrating parenchymal veins of the spinal cord and meninges. With the formation of large demyelinated plaques in the spinal cord, massive fibrosis of the meninges with infiltration by inflammatory cells was noted in an area covering the surface of the lesion. In plaques which reach the spinal cord surface, inflammatory cells could be seen passing between the pia and the spinal cord substance. In chronic remyelinated lesions, adhesions between meningeal fibroblasts and the astroglial limiting membrane were seen. In addition a topographical correlation between the distribution of spinal cord veins and venules and demyelinated plaques was found. These observations indicate that spinal cord lesions in chronic relapsing EAE are initiated by perivenous inflammation in the parenchyma and the meninges. Plaque formation, especially in spinal cord surface lesions, is additionally enhanced by the entrapment of inflammatory cells in the fibrosed meninges. The exchange of macrophages through the glia-limiting membrane may be responsible for the more rapid debris removal in the spinal cord in comparison with brain lesions in chronic relapsing EAE.     

Initial remission period in insulin-dependent diabetes in the young subject

Occurrence of a remission after initiation of insulin treatment in insulin dependent diabetes (type I) of recent onset is a well known phenomenon. It may be more or less complete up to insulin withdrawal. In newly diagnosed IDD requiring insulin for ketoacidosis or primary failure of oral agents and with a duration of symptoms of less than 6 months, initiation of optimized insulin therapy was followed by suppression of insulin (with or without the use of oral agents) in two thirds of cases for a mean period of 12 months while blood glucose and glycosylated haemoglobin remained normal. As therapeutic reversal of the etiopathological mechanism of IDD is foreseen it is relevant to define the characteristics of cases with remission induced by intensified insulin treatment, and the mechanisms by which they may be explained. Current knowledge on these questions will be analysed in this review. Furthermore it appears that withdrawing insulin for a mean period of 12 months does not hamper the subsequent control of diabetes.     

Influence of palmitate and oleate on the binding of warfarin to human serum albumin: stopped-flow studies

The rate of transition from an unstable to a stable complex and the dependence of this on the number of fatty acid ligands present was determined for the binding of warfarin on human serum albumin. When oleate or palmitate was added in amounts up to 2:1 excess to human serum albumin solutions the measured rate constant for the transition (k2) was increased in comparison with fatty acid free albumin. When the fatty acid concentration is further increased, k2 decreases. When the fatty acid level is 2 to 3 mol per mol albumin, the affinity constant (KA) is higher than for fatty acid free solutions. With higher ratios the value for KA is reduced. According to the observed changes in kinetic parameters, the binding of warfarin is apparently affected allosterically. A reduced plasma protein binding of coumarins should be expected when fatty acid levels are raised over a prolonged period.