Zur Klinik und Neuropathologie der subakuten präsenilen spongiösen Atrophien mit dyskinetischem Endstadium

Zusammenfassung Innerhalb der Gruppe der “pr?senil-involutiven subakuten myoklonisch-dyskinetischen Encephalopathien” gewinnen die “subakuten pr?senilen spongi?sen Atrophien mit dyskinetischem Endstadium” eine Sonderstellung.McMenemey u. Nevin (1955) hatten erstmals deren klinisch-neuropathologische Bedeutung als einheitliches Syndrom erkannt. Das Krankheitsbild unterscheidet sich nicht so sehr klinisch als in der morphologischen Proze?struktur sowohl von derJakob-Creutzfeldschen Krankheit als von pr?senilen Krankheitsbildern, welche vonAlajouanine, van Bogaert, Garcin, Betrand, Gruner u. Brion (1950) beschrieben wurden, ma?geblich dadurch, da? der morphologische Proze? nicht prim?r an den Ganglienzellen, sondern am “zwischenzelligen Gewebe” angreift. Hierdurch rücken die Vorg?nge gewebslokalisatorisch in die N?he seniler Gewebsver?nderungen nach Art der Drusenbildung, von welchen sie sich jedoch — im Sinne eines “gegenl?ufigen” Verhaltens — u. a. durch das Fehlen von Ausf?llungs-und Ablagerungsmechanismen sowie Abbauvorg?ngen des Gewebes vermittels der Glia unterscheiden. Dies wird im Speziellen unter Würdigung der Ergebnisse elektronenoptischer und histochemischer Untersuchungen zur Frage der “Grundsubstanz” er?rtert. In erster Linie kam es darauf an, einen Beitrag zurDifferentialdiagnose der im deutschen Schrifttum noch nicht hinreichend gewürdigten“pr?senil-involutiven subakuten myoklonisch-dyskinetischen Encephalopathien” zu geben. Mit 7 Textabbildungen     

Increased incidence of jugular valve insufficiency in patients with transient global amnesia

Objective While transient global amnesia (TGA) is a clinically well defined disorder, its etiology is poorly understood. Cerebral venous hypertension and subsequent damage to hippocampal and diencephalic structures are among the discussed hypothetical causes. Using a direct method for the study of retrograde flow during a Valsalva maneuver, we determined whether jugular valve insufficiency contributes to cerebral venous hypertension in patients with TGA. Methods Jugular valve closure was assessed by duplex sonography in 20 patients with TGA and 20 age and gender matched controls. The diagnosis of valvular insufficiency was made on the basis of recently established criteria. Results Valvular insufficiency (either left or rightsided, or bilateral) was identified in 85% of patients with TGA,and in 45% of controls (p = 0.008). All patients with involuntary Valsalva episodes immediately prior to TGA developed valvular insufficiency (n = 8; p = 0.13 compared with patients who did not recall such an event). The mean duration of the insufficiency jet did not differ significantly between patients with TGA (3.26s) and controls (2.78s; p = 0.315). However, patients with TGA who experienced a trigger event were characterized by significantly longer insufficiency reflux times (3.84s) than those without (2.55s; p = 0.03). Conclusions TGA is associated with an increase in the prevalence of jugular insufficiency. Valvular insufficiency may lead to increased venous pressure transmission during a Valsalva maneuver and thus contribute to venous ischemia in TGA. The association of valvular insufficiency and longer reflux times with the occurrence of a trigger event further suggests that cerebral venous congestion is an important etiological factor in transient global amnesia.     

Transition Metal Compounds Towards Holography

We have successfully proposed the application of transition metal compounds in holographic recording media. Such compounds feature an ultra-fast light-induced linkage isomerization of the transition-metal–ligand bond with switching times in the sub-picosecond regime and lifetimes from microseconds up to hours at room temperature. This article highlights the photofunctionality of two of the most promising transition metal compounds and the photophysical mechanisms that are underlying the hologram recording. We present the latest progress with respect to the key measures of holographic media assembled from transition metal compounds, the molecular embedding in a dielectric matrix and their impressive potential for modern holographic applications.     

Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization

Inhalation of silica crystals causes inflammation in the alveolar space. Prolonged exposure to silica can lead to the development of silicosis, an irreversible, fibrotic pulmonary disease. The mechanisms by which silica and other crystals activate immune cells are not well understood. Here we demonstrate that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3. NALP3 activation required phagocytosis of crystals, and this uptake subsequently led to lysosomal damage and rupture. 'Sterile' lysosomal damage (without crystals) also induced NALP3 activation, and inhibition of either phagosomal acidification or cathepsin B activity impaired NALP3 activation. Our results indicate that the NALP3 inflammasome senses lysosomal damage as an endogenous 'danger' signal.     

The NALP3 inflammasome is involved in the innate immune response to amyloid-beta

The fibrillar peptide amyloid-beta (A beta) has a chief function in the pathogenesis of Alzheimer's disease. Interleukin 1 beta (IL-1 beta) is a key cytokine in the inflammatory response to A beta. Insoluble materials such as crystals activate the inflammasome formed by the cytoplasmic receptor NALP3, which results in the release of IL-1 beta. Here we identify the NALP3 inflammasome as a sensor of A beta in a process involving the phagocytosis of A beta and subsequent lysosomal damage and release of cathepsin B. Furthermore, the IL-1 beta pathway was essential for the microglial synthesis of proinflammatory and neurotoxic factors, and the inflammasome, caspase-1 and IL-1 beta were critical for the recruitment of microglia to exogenous A beta in the brain. Our findings suggest that activation of the NALP3 inflammasome is important for inflammation and tissue damage in Alzheimer's disease.     

The DNA sugar backbone 2' deoxyribose determines toll-like receptor 9 activation

CpG motifs within phosphorothioate (PS)-modified DNA drive Toll-like receptor 9 (TLR9) activation, but the rules governing recognition of natural phosphodiester (PD) DNA are less understood. Here, we showed that the sugar backbone determined DNA recognition by TLR9. Homopolymeric, base-free PD 2' deoxyribose acted as a basal TLR9 agonist as it bound to and activated TLR9. This effect was enhanced by DNA bases, even short of CpG motifs. In contrast, PS-modified 2' deoxyribose homopolymers acted as TLR9 and TLR7 antagonists. They displayed high affinity to both TLRs and did not activate on their own, but they competitively inhibited ligand-TLR interaction and activation. Although addition of random DNA bases to the PS 2' deoxyribose backbone did not alter these effects, CpG motifs transformed TLR9-inhibitory to robust TLR9-stimulatory activity. Our results identified the PD 2' deoxyribose backbone as an important determinant of TLR9 activation by natural DNA, restrict CpG-motif dependency of TLR9 activation to synthetic PS-modified ligands, and define PS-modified 2' deoxyribose as a prime effector of TLR9 and TLR7 inhibition.     

Color-coded duplex ultrasonography of the origin of the vertebral artery: normal values of flow velocities.

The introduction of color-coded duplex ultrasonography has improved the ease of performing ultrasound investigations of the vertebral arteries. So far, normal values of flow velocities have been reported only for the intertransverse region of the vertebral artery (V2 segments). Atherosclerotic disease at the origin of the vertebral arteries (V0 segment) is frequent and is one of the risk factors for vertebrobasilar ischemic disease. Normal values of flow velocities of the vertebral artery origin are needed to assess pathologic findings, such as vertebral artery origin stenosis or dissection. The aim of this study was to describe the normal flow velocities of vertebral artery origin (V0 segment) and the pre- (V1 segment) and intertransverse (V2 segment) part in 50 age-matched neurologic patients (mean age 54) without ischemic cerebral disease. The V0 segment could be visualized in 46 persons (92%) on the right side and in 43 (86%) on the left. The peak systolic blood velocity ranged from 30 to 100 cm/s (mean 63.6 +/- 17.5 cm/s), and end-diastolic blood velocity ranged from 10 to 35 cm/s (mean 16.1 +/- 5.1 cm/s). Analysis of side-to-side differences showed no significant differences of flow velocities in all subjects. It is concluded that color duplex ultrasonography is a feasible method to insonate the origin of the vertebral artery, and that nomogram data could be established. It is suggested that color-coded duplex ultrasonography of the vertebral artery origin should be performed in all patients with clinical symptoms or signs of vertebrobasilar ischemic disease. Nevertheless, further studies are needed to determine the normal and pathologic values of flow velocities of the vertebral artery origin and their reproducibility.     

Cytogenetische Untersuchungen an einem heterotransplantablen Ascites-Hepatom in vivo und im Explantat

Zusammenfassung Ein Hepatom der Ratte, das in Ascitesform wächst, wurde unter verschiedenen Bedingungen untersucht. Dabei liegt die Chromosomenzahl bei der Entwicklung auf der Ratte, im Goldhamster und in der Gewebekultur in der gleichen Größenordnung. In jedem Falle findet sich ein Maximum der Chromosomenzahlen im polyploiden Bereich und ein zweites bei 66. Ein nachweisbares Markierungschromosom mit heterochromatischen Schenkeln findet sich in allen Stämmen in gleicher Prozentzahl. Die Überführung in Gewebekultur führt zum gehäuften Auftreten von Endoreduplikationen und zur Vermehrung der polyploiden Chromosomenzahlen.

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Summary A hepatoma of the rat, which grows in the ascites form, was studied under various conditions. As the tumor grew in the rat, in the gold hamster, and in tissue culture, its chromosome number remained at the same magnitude. In each instance a maximum of the chromosome numbers was found in the polyploid range, a second maximum was at 66. A demonstrable marker-chromosome with heterochromatic limbs was found in all strains in the same percentage. The transfer to tissue culture led to an increase of endomitoses and to an increase of the polyploid chromosome numbers.

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Mit 4 Textabbildungen

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Herrn Prof. Dr. F. Wassermann, Chicago, zum 80. Geburtstag gewidmet.

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Die Durchführung der Arbeit wurde von der Deutschen Forschungsgemeinschaft unterstützt.     

Kunstfehler, Ärzterecht

International Journal of Legal Medicine -