Large-scale suspension culture with limited facilities

Methods in Cell Science -     

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.     

Mosaic hexasomy 21.

Cases in which there are more than three copies of a sex chromosome, and rarely of an autosome, have been reported, but to our knowledge hexasomy has never been described except in tissue undergoing neoplastic change. This report describes a female infant with multiple malformations in whom we found a mosaic hexasomy 21. This was first detected in amniotic fluid cells and subsequently in skin fibroblasts.     

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     

Towards the understanding of muscle contraction and its regulation,A Symposium in honor of John Gergely,MD, PhD

Journal of Muscle Research and Cell Motility -     

Day-night differences in estimated rates of 5-hydroxytryptamine turnover in the rat pineal gland

Summary Rates of 5-hydroxytryptamine synthesis in various brain tissues can be estimated from the linear increase in 5-hydroxytryptophan levels following inhibition of 5-hydroxytryptophan decarboxylation with RO4-4602 or NSD-1015. In addition, NSD-1015 can prevent 5-hydroxytryptamine oxidative-deamination via monoamine oxidase inhibition, leading to linear decreases in a major metabolite of this amine, 5-hydroxyindole acetic acid. In the rat pineal gland we demonstrated similar increases in 5-hydroxytryptophan levels after nocturnal or diurnal injection of RO4-4602 (100 mg · kg^–1) or NSD-1015 (200 mg · kg^–1). Similar decreases in 5-hydroxyindole acetic acid were also observed after nocturnal or diurnal injection of NSD-1015 or pargyline (an inhibitor of monoamine oxidase) (75 mg · kg^–1). 5-Hydroxytryptamine levels increased after nocturnal pargyline injection but remained constant after diurnal pargyline administration. 5-Hydroxytryptamine levels exhibited little change following nocturnal injection of NSD-1015 but decreased linearly after diurnal injection of NSD-1015. We suggest that (1) rat pineal 5-hydroxytryptamine synthesis is increased nocturnally, (2) metabolic utilization, primarily by oxidative-deamination, of 5-hydroxytryptamine is increased diurnally and (3) basal levels of pineal 5-hydroxytryptamine may be stored within adrenergic nerve endings which innervate the pinealocytes responsible for synthesizing this amine, thus protecting or otherwise making unavailable this pool of 5-hydroxytryptamine for metabolic utilization.     

B-cell function in patients with chronic lymphocytic leukemia

Summary Using a reverse hemolytic protein A plaque assay, spontaneous and pokeweed mitogen (PWM)-induced immunoglobulin (Ig) secretion was determined in peripheral blood from 22 patients with B₁-chronic lymphocytic leukemia (CLL), one patient with B₂-CLL, and one patient with suppressor T-CLL. Diagnoses were established by cytological and histological criteria as well as several marker analyses. Lymphocytes from B₁- and B₂-CLL patients were unable to secrete Ig either spontaneously or after PWM stimulation. In T-CLL lymphocytes, spontaneous Ig secretion was suppressed very probably by the OKT-8-positive leukemic population, since, after cultivation with PWM, a normal Ig secretion could be demonstrated which was paralleled by a decrease in the OKT-8-positive cells. Cocultivation experiments with freshly isolated, unseparated lymphocytes from normal subjects and lymphocytes from patients were of no informational value, since isolated normal B-cells alone already showed a high rate of Ig secretion. However, coculture experiments with separated subpopulations after PWM stimulation revealed an intrinsic B-cell defect in lymphocytes from B₁-CLL patients, whereas their T-lymphocytes were found to be normal helper cells.

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Abbreviations CLL Chronic lymphocytic leukemia - PWM Pokeweed mitogen - ISC Immunoglobulin-secreting cells - Ig Immunoglobulin(s) Supported by the Deutsche Forschungsgemeinschaft (Ru 215/2)