Niemann-Pick disease

Summary The results of a complex analysis of liver tissue are presented (four biopsy and two autopsy samples) obtained from six patients with Niemann-Pick disease (NPD) with a gross deficiency of sphingomyelinase (SMase) accompanied by a typical increase in sphingomyelin (SM). There were five cases of NPD type A (four of them with an atypical, prolonged course) and one case of type B. By means of lipid histochemistry it was possible to demonstrate SM storage both in hepatocytes and in the reticuloendothelial system (RES) of the liver (Kupffer cells and portal macrophages) and to show in two siblings with NPD type A a so-far undescribed centrilobular storage pattern. Enzyme histochemistry revealed a secondary deficit of nonspecific esterase activity and acid -galactosidase in liver storage macrophages and varying degrees of suppression of hepatocytic enzyme activities as a reaction to lipid storage of sudden onset. Ultrastructurally, it was possible to demonstrate cholesterol in lysosomes by using digitonin fixation, the involvement of Ito cells in lipid storage, the aggregation of storage lysosomes with certain other organelles and their occasional connections with the endoplasmic reticulum. The problems of possible lipid extraction during processing were considered as a cause of pronounced lysosomal electron-lucidity and of the ultrastructural identification of the participating lipopigment. The significance of the findings is discussed in relation to the existing classification and, particularly, to the stored lipid dilemma of cases of NPD type C.     

Postaggressionsstoffwechsel nach Herzinfarkt — dargestellt am Verhalten kurzlebiger Plasmaproteine

Zusammenfassung Die Kinetik kurzlebiger Plasmaproteine im Postaggressionssyndrom wurde vergleichend bei Patienten nach Herzinfarkt (HI) mit und ohne klinische Komplikationen und nach Angina Pectoris-Anfall (AP) am Beispiel der Akut-Phase-Proteine ₁-Antitrypsin, C-reaktives Protein, Fibrinogen und Haptoglobin sowie der Transportproteine Präalbumin und Transferrin nach der Methode der radialen Immundiffusion untersucht. Während AP keinen Einfluß auf die Proteinkinetik ausübt, zeigen sich nach HI ein kontinuierlicher Anstieg der Akut-Phase-Proteine und ein dazu parallel verlaufender Abfall der Transportproteine mit Maximal- bzw. Minimal-Konzentrationen zwischen dem 3. und 5. Tag nach dem Ereignis und anschließender Rückbildung zu den Ausgangswerten. Die Veränderungen, die in ähnlicher Weise auch nach chirurgischen Traumata beobachtet werden, sind abhängig vom Schweregrad der Erkrankung und entsprechend prognostisch verwertbar.Im Postaggressionssyndrom wird demnach das Verhalten der nahrungsabhängigen Proteine Präalbumin und Transferrin sowohl durch Art und Stärke des Streßeinflusses als auch durch den Ernährungszustand beeinflußt. Der Mechanismus dieser Veränderungen und die Konsequenzen für die Verwendung der Proteine als diagnostische Kenngrößen werden diskutiert.     

Feinstrukturell-morphometrische Befunde an der Kammerwand hypertrophierter menschlicher linker Ventrikel

Zusammenfassung An den KammerwÄnden menschlicher linker Ventrikel, die auf Grund einer Aortenstenose, einer Aorteninsuffizienz oder eines kombinierten Aortenvitium hypertrophiert waren, wurden licht- und elektronenmikroskopisch morphometrische Untersuchungen angestellt. Die Ergebnisse wurden mit denen, die an nicht belasteten menschlichen linken Ventrikeln gewonnen wurden, verglichen.Lichtmikroskopisch unterscheiden sich die Anteile der Volumendichten des Interstitium und der Herzmuskelzellen am gesamten Herzmuskelgewebe nicht statistisch signifikant. Es konnte morphometrisch eine Zellvergrö\erung festgestellt werden, die aus der signifikanten Verringerung der Volumendichte der Zellkerne (P<0,001) und der Anzahl der Zellkerne pro TestflÄche (P<0,0001) gegenüber den beiden Normalkollektiven resultiert. Elektronenmikroskopisch ist eine Zunahme der Volumendichten der Myofibrillen (P<0,0001) auf Kosten des restlichen Cytoplasmas (P<0,001) festzustellen, wÄhrend die Volumendichte der Mitochondrien im Vergleich mit den jungen und alten Patienten abnahm (P<0,0001). Die OberflÄchendichte der Mitochondrien verringerte sich gegenüber den beiden Vergleichskollektiven (P<0,001) ebenso wie die der Cristae mitochondriales (P<0,0001). Diese Ergebnisse finden ihr morphologisches Korrelat in Mitochondriendestruktionen. Eine vermehrte Myolyse hat bei den hypertrophierten Herzen, die alle gewichtsmÄ\ig über dem kritischen Herzgewicht lagen, noch nicht eingesetzt. Bei allen Patienten wurde der herzchirurgische Eingriff mit Erfolg durchgeführt.

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Ultrastructural morphometric analysis of hypertrophied human myocardial left ventricles

Summary Biopsies of hypertrophied human myocardial left ventricles were investigated morphometrically. The diagnoses of the patients were stenosis of the aortic valve, aortic insufficiency or a combination of both lesions. The results were compared with those from normally loaded human left ventricles.There are no differences on light microscopical level between the volume densities of interstitial tissue and of heart muscle cells in the three groups of patients. A significant diminution of the volume density of the nuclei (P<0.001) and the number of nuclei per test area (P<0.0001) when compared with normal groups suggests an increase in volume of the single heart muscle cell. The ultrastructural study shows marked increase in volume density of myofibrils (P<0.0001), with accompanying decrease in the volume densities of mitochondria (P<0.0001) and the remaining cytoplasm (P<0.001). A gross decrease in the surface area of mitochondria (P<0.001) and of cristae mitochondriales (P<0.0001) is found. The morphological equivalents of this result are numerous stages of mitochondrial destruction including cristolysis. All myocardial weights were beyond the critical heart weight.

Mit dankenswerter Unterstützung der Deutschen Forschungsgemeinschaft über den Sonderforschungsbereich SFB 104     

A Role for Interferon- β in Guillain-Barré Syndrome?

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating neuropathy that is associated with long-lasting morbidity and a substantial risk of mortality. The 2 reference treatments, plasma exchange and intravenous immunoglobulins (IVIg), do not change the functional prognosis for the most severely ill patients. The pathogenesis of GBS involves humoral and cellular immune dysfunctions that have only recently been characterised. Antibodies to nerve antigens may participate in complement activation, antibody-dependent macrophage cytotoxicity and reversible conduction failure. The cellular immune reaction is associated with increases in pro-inflammatory cytokines [such as tumour necrosis factor-alpha (TNFalpha)] and matrix metalloproteinases (MMPs; e.g. MMP-9), and a decrease in anti-inflammatory cytokines [such as transforming growth factor-beta1 (TGFbeta1)]. All the changes favour adhesion to and transmigration across the endothelium of immune cells, a key phenomenon associated with GBS. Recovery from GBS is characterised by the normalisation of these changes. Experimental allergic neuritis (EAN), the experimental model of GBS, has strikingly similar immunological characteristics. The usual treatment options for patients with GBS (plasma exchange and IVIg) mainly target the humoral component of the immune response. Interferon-beta (IFNbeta) is a cellular immunomodulator that inhibits antigen presentation and TNFalpha production and binding, and modulates macrophage properties. IFNbeta increases anti-inflammatory T cell functions and the production of anti-inflammatory cytokines, such as TGFbeta1. IFNbeta has important effects on leukodiapedesis, caused by modulating the expression of cell adhesion molecules and the MMP-9 proteinases. It has been used with success in EAN, in some patients with acute exacerbation of chronic inflammatory demyelinating polyneuropathy, and in 1 patient with GBS. The pathophysiology of patients with GBS, an understanding of IFNbeta properties and results of experimental studies support the investigation of IFNbeta in trials of patients with GBS.     

Clinical Significance of Epithelial Peptide Antibiotics

Although the epithelium of macro-organisms is constantly exposed to microbial threats, infections are rather rare. Antimicrobial substances produced by epithelial cells may explain the high natural resistance of the exposed epithelia. Gene-encoded antimicrobial peptides that are believed to kill micro-organisms via pore formation have been found in the surface cells and secretions of plants and insects, and in the skin of frogs. The tongues and lungs of cattle are usually free of infection, and the first mammal-derived epithelial antimicrobial peptides, which belong to the so-called beta-defensin family, were discovered in bovine trachea and tongue. These beta-defensins are induced by infections and inflammatory agents, and are upregulated in specific anatomical sites of the epithelia, where infections occur. Recent studies have revealed that human epithelia also express beta-defensins: the tissues of the urogenital tract constitutively express human beta-defensin-1 (HBD-1), and a second human beta-defensin, HBD-2, is produced in skin and lung upon stimulation of epithelial cells with infectious or inflammatory agents. This brief review summarises our current knowledge about epithelial antimicrobial peptides, and discusses their possible role and relevance in the clinic. This includes the possibility of defective production in patients with recurrent infections, the therapeutic use of synthetic antimicrobial peptides, and the induction of their synthesis as an alternative strategy to prevent infections.     

Transducers for foot pressure measurement: survey of recent developments

Recent advances in the development of transducers for the measurement of vertical and shear forces acting on the plantar surface of the foot are reviewed. Barefoot and in-shoe discrete and matrix transducers are reviewed in terms of structure, operation, performance and limitations. Examples of capacitive, piezoelectric, optical, conductive and resistive types of transducer are presented. Where available, the current clinical status is specified.     

Amnesic effects of bilateral lesions placed in the hyperstriatum ventrale of the chick after imprinting

Summary The purpose of this study was to investigate whether bilateral lesions to a part of the hyperstriatum ventrale (IMHV) impair retention if they are placed after chicks have been imprinted. Domestic chicks were hatched and reared in darkness and exposed to an imprinting (training) stimulus for 2 h commencing 22 h post hatch. The chicks were then anaesthetised and bilateral lesions placed in IMHV (N = 16) birds, hyperstriatum accessorium (HA; N = 16) or the lateral part of the cerebral hemispheres (LCA; N = 16). Forty-eight sham-operated chicks served as controls. Chicks were returned to the dark incubator, and, 15–20 h after the operation, their approach towards the training stimulus and to a second novel stimulus was measured. The controls and the chicks with lesions in HA and LCA showed a strong preference for the training stimulus and hence a high level of retention. The preferences of these three experimental groups did not differ significantly from one another. The mean preference of chicks with lesions in IMHV was significantly less than that of the sham-operated controls (P<0.01) and of chicks lesioned in HA (P<0.05). Bilateral lesions to IMHV therefore selectively impair retention of a preference acquired through imprinting. This impairment is unlikely to be a non-specific consequence of defective sensory processing or motor performance because the four groups did not differ from each other in (i) the time taken accurately to peck a rocking bead, (ii) the accuracy of pecking millet seeds and (iii) the performance of a simultaneous visual discrimination task involving heat reinforcement.Supported by grants from the Science Research Council, the Leverhulme Trust, the Wellcome Trust and FAPESP (Brazil)     

Die Beurteilung des Kollagenstoffwechsels mittels Hydroxyprolin im Serum und Urin und der Serum-Kollagenpeptidase unter verschiedenen Diätformen

Zusammenfassung Zur Klärung der Frage, ob zwischen Bergleuten mit einer Silikose und Gesunden Unterschiede in der Ausscheidung von Hydroxyprolin (HP) im Sammelurin bestehen und ob diese Messung durch einfacher zu bestimmende Parameter ersetzt werden kann, wurden an insgesamt 34 Probanden HP-Bestimmungen im Sammelurin und im Blutserum sowie die Bestimmung der Serum-Kollagenpeptidase durchgeführt.Die HP-Bestimmungen im Urin und Serum unter verschiedenen Diätformen zeigen, daß eine 24stündige prolinarme Diät vor Beginn der Urinsammelperiode sowie die Weiterführung während der Sammelperiode genügt. Das peptidgebundene HP — bestimmt aus der Differenz von Gesamt-HP und dem ohne Hydrolyse gemessenen HP — weist keine Unabhängigkeit von der Diät auf. Zu den HP-Mengen im Sammelurin haben die Serumwerte eine enge Parallelität. Allein die Kollagenpeptidase ist von der Diät unabhängig und scheint ein geeignetes Maß zur Beurteilung der Aktivität des Kollagenstoffwechsels zu sein.Zwischen Bergleuten mit einer Silikose und Gesunden fanden sich keine Unterschiede.Mit finanzieller Unterstützung der Bergbau-Berufsgenossenschaft Bochum