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Peter Schuff-Werner

Publications and source records attributed to Peter Schuff-Werner.

28 records · Page 2Linked to original sources
PubMed2002

Oxidative stress in phagocytes--"the enemy within".

Phagocytes represent a powerful defense system against invading microorganisms that threaten the life or functional integrity of the host. The capacity to generate and release substantial amounts of reactive oxygen species is a unique property of activated polymorphonuclear and mononuclear phagocytes. The crucial role of these molecules in killing microorganisms and their consecutive contribution to tissue damage during injury and inflammation is widely known. Although much research has been done to explore the molecular events involved in the interaction of oxygen intermediates with microbes or host tissue, surprisingly little attention has been paid to the effect of reactive metabolites on the phagocyte itself. This fact is especially surprising, since it is apparent that the activated phagocyte is directly exposed to its own toxic metabolites. The potential damage occurring during excessive radical formation might notably alter the vital functions of these primarily immunocompetent cells. Moreover, the critical role of oxygen radicals in apoptosis of leukocytes has been recently revealed. Apoptosis is now supposed to represent a key mechanism in neutrophil deactivation and resolution of inflammation. Therefore, this review will focus on the delicate balance between released oxidants and antioxidative protection within the phagocytes themselves. General and phagocyte-specific antioxidative mechanisms, which have co-evolved with the radical generating machinery of phagocytes, are discussed, since the outcome of local inflammation can directly depend on this antioxidative capacity and might range from adequate elimination of the pathogen with minimal acute tissue damage to progression towards a systemic inflammatory response syndrome.

Animals↗
PubMed2002

Comparison of two filter combinations for low-density lipoprotein apheresis by membrane differential filtration: a prospective crossover controlled clinical study.

Membrane differential filtration is an accepted procedure for the extracorporeal removal of low-density lipoprotein (LDL). Reduction rates largely depend on the nature of the membranes and are ideally evaluated in a crossover study design. Four patients who had been treated by LDL apheresis for at least 6 months were included. Six consecutive weekly sessions (40 ml plasma/kg body weight) were scheduled per system (Plasmacure PS06/Evaflux Eval 5A [Kuraray] versus Plasmaflo OP05W/Cascadeflo AC1770 [Asahi]). Laboratory measurements indicated reductions of plasma concentrations for fibrinogen (37% [Kuraray] versus 44% [Asahi]), IgG (15% versus 20%), IgA (24% versus 28%), IgM (63% versus 53%), and total protein (11% versus 16%). Total cholesterol was eliminated by 52% versus 49%, LDL by 67% versus 66%, triglycerides by 56% versus 41%, and high-density lipoprotein by 10% versus 20%. Three therapies employing the Asahi filter combination were terminated prematurely due to saturation of the plasma fractionator. In conclusion, despite similar physical properties, the membranes differ significantly concerning selectivity and sensitivity to saturation.

Aged↗
PubMed2002

Selective hemapheresis, an effective new approach in the therapeutic management of disorders associated with rheological impairment: mode of action and possible clinical indications.

The in vitro measurement of whole-blood viscosity, plasma viscosity, and erythrocyte aggregability is easy to perform, but they only allow a partial insight into the complexity of blood flow characteristics; however, they permit definition of the rheological properties of new hemorheological therapeutic modalities such as extracorporeal plasma therapy as described in this paper. Under more theoretical aspects, it becomes obvious that such hemorheological approaches should either improve the vasomotoric properties of blood vessels, reduce the circulating red blood cell concentration, or improve the viscosity by reducing the concentration of hemorheologically relevant plasma proteins. In this review, the rheological effect of a single apheresis treatment with different devices was compared. Due to their differences in selectivity, the extracorporeal methods have different effects on the rheologically relevant plasma proteins, and, therefore, their rheological effectiveness differs remarkably. Today, the classical blood letting and plasma exchange treatment have been replaced by erythrapheresis and selective devices for extracorporeal plasma treatment, respectively. For more than 10 years, the following 5 more-or-less selective apheresis procedures are commercially available: immunoadsorption, differential filtration, polyanion adsorption by dextrane sulfate as well as by polyacrylate, and polyanion precipitation by heparin as polyanion. The last three procedures are semiselective and, therefore, relatively unspecific whereas immunoadsorption only affects the plasma lipoprotein concentration. Several studies have shown the effective use of extracorporeal hemorheotherapy for the treatment of various diseases including macro- and cryoglobulinemia, Raynaud's disease, hyperlipoproteinemia (often characterized by premature atherosclerosis and coronary heart disease and peripheral arterial occlusive disease), cerebral multi-infarct demention and acute ischemic stroke, sudden hearing loss, and acute occlusion of the central retinal artery.

Arterial Occlusive Diseases↗
PubMed2002

A homozygous HFE gene splice site mutation (IVS5+1 G/A) in a hereditary hemochromatosis patient of Vietnamese origin.

The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described mutation alters the invariant G at position +1 of the 5' splice site causing altered mRNA splicing and exon skipping with exon 4 being spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE splice site mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene mutation in Caucasian subjects suggests that the mutation is exclusive to this family, mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients.

Asian People↗
PubMed2002

Expression and regulation of calpain in rat pancreatic acinar cells.

INTRODUCTION: Calpains, cytosolic Ca(2+)-dependent cysteine proteases, are expressed in a variety of mammalian cells and have been found to participate in stimulus-secretion coupling in platelets and alveolar cells. AIMS: In pancreatic acinar cells, expression of calpains and their role in the secretory process have not yet been elucidated. Both subjects, therefore, were examined in the current study. METHODOLOGY: mu-calpain and m-calpain were detected immunochemically. Calpain activation was measured by fluorescence spectrophotometry and single-cell fluorometry using Suc-Leu-Leu-Val-Tyr-AMC as substrate. Amylase secretion and cell damage, characterized by lactate dehydrogenase release, were measured by colorimetric assays. RESULTS: Immunochemistry revealed cytoplasmic localization of both calpain isoforms. Immediately after increasing the cytosolic Ca(2+) concentration with ionomycin, a marked dose-dependent protease activation and cellular damage were observed. Inhibition of ionomycin-mediated enzyme activation through preincubation of cells with Ca(2+)-free medium, BAPTA-AM, or Z-Leu-Leu-Tyr-CHN(2) significantly reduced cell injury. Cholecystokinin (100 pM) also induced proteolytic activity, preceding cholecystokinin-stimulated amylase secretion. Protease activity and amylase release were significantly inhibited by Z-Leu-Leu-Tyr-CHN(2 ) retreatment. CONCLUSION: Calpains are expressed in pancreatic acinar cells and may participate in stimulus-secretion coupling. In addition, our study indicates that pathologic calpain activation may contribute to Ca(2+)-mediated acinar cell damage.

Amylases↗