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Biomedical subjects

O Schulz

Publications and source records attributed to O Schulz.

At least 19 recordsLinked to original sources
PubMed1999

The cysteine protease activity of the major dust mite allergen Der p 1 selectively enhances the immunoglobulin E antibody response.

The house dust mite Dermatophagoides pteronyssinus allergen Der p 1 is the most immunodominant allergen involved in the expression of dust mite-specific immunoglobulin (Ig)E-mediated hypersensitivity. The reason for this potent IgE-eliciting property of Der p 1 remains unknown, but there is mounting in vitro evidence linking the allergenicity of Der p 1 to its cysteine protease activity. Here we demonstrate for the first time that immunization of mice with proteolytically active Der p 1 results in a significant enhancement in total IgE and Der p 1-specific IgE synthesis compared with animals immunized with Der p 1 that was irreversibly blocked with the cysteine protease inhibitor E-64. We conclude that the proteolytic activity of Der p 1 is a major contributor to its allergenicity.

Allergens↗
PubMed1999

High-dose enoximone to evaluate reversibility of pulmonary hypertension: is there a diagnostic value of neurohormonal measurements?

BACKGROUND: Heart transplantation is associated with a reduction of the neurohumoral activation seen in patients with severe congestive heart failure. In this study, we investigated whether pharmacologically induced complex hemodynamic improvement during assessment of reversibility of pulmonary hypertension with a phosphodiesterase inhibitor is able to induce neurohormonal changes of diagnostic importance. METHODS AND RESULTS: Twenty-one patients with New York Heart Association class III-IV heart failure underwent infusion of 3 mg/kg enoximone over a period of 30 minutes. Before and after drug infusion, we determined the plasma concentrations of atrial natriuretic peptide, endothelin-I, angiotensin-II, aldosterone, norepinephrine, epinephrine, and angiotensin-converting enzyme activity sampled from a peripheral vein and the pulmonary artery. In addition to the expected significant reduction of pulmonary hypertension and enhancement of cardiac output, increased levels of the vasoconstrictors endothelin-I, angiotensin-II, and norepinephrine were observed. Aldosterone fell after enoximone infusion; a higher baseline aldosterone level correlated to the degree of reduction of the pulmonary arteriolar resistance by enoximone. Baseline atrial natriuretic peptide levels correlated with parameters, indicating the severity of heart failure. However, the plasma concentration of this peptide did not change significantly after enoximone infusion. CONCLUSIONS: Acute hemodynamic improvement after enoximone bolus in candidates for heart transplantation is not accompanied by a reduction of the enhanced neurohumoral activity in these patients. The reaction of the investigated hormones cannot predict the individual degree of reversibility of pulmonary hypertension.

Angiotensin II↗
PubMed1999

Paralysis of dendritic cell IL-12 production by microbial products prevents infection-induced immunopathology.

Interleukin-12 plays a major role in immunity to intracellular pathogens by governing the development of IFNgamma-dependent host resistance. Nevertheless, unregulated IL-12 synthesis can lead to immunopathology, an outcome prevented by the concurrent expression of interleukin-10. Dendritic cells (DC) are an important source of the initial IL-12 stimulated by microbial agents. Here, we show that, following systemic triggering, DC can no longer be restimulated to produce IL-12 in vivo while continuing to respond in vitro. When infected with Toxoplasma gondii during this refractory state, mice mount impaired acute IFNgamma responses and, in the case of IL-10-deficient animals, are protected from cytokine-induced mortality. These findings demonstrate a previously unrecognized form of immunologic paralysis involving DC that can protect from infection-induced immunopathology.

Animals↗
PubMed1998

Proteolytic cleavage of CD25, the alpha subunit of the human T cell interleukin 2 receptor, by Der p 1, a major mite allergen with cysteine protease activity.

Recent reports have indicated that the cysteine protease activity of Der p 1 may play a significant role in its ability to elicit IgE antibody responses, mainly through cleavage of membrane CD23 on B cells and interleukin (IL)-4 synthesis and secretion from mast cells and basophils. Here we demonstrate for the first time that Der p 1 also cleaves the alpha subunit of the IL-2 receptor (IL-2R or CD25) from the surface of human peripheral blood T cells and, as a result, these cells show markedly diminished proliferation and interferon gamma secretion in response to potent stimulation by anti-CD3 antibody. Given that the IL-2R is pivotal for the propagation of Th1 cells, its cleavage by Der p 1 may consequently bias the immune response towards Th2 cells, thereby creating an allergic microenvironment.

Allergens↗
PubMed1998

Influence of muscle forces on femoral strain distribution.

Musculoskeletal loading influences the stresses and strains within the human femur and thereby affects the processes of bone modeling and remodeling. It is essential for implant design and simulations of bone modeling processes to identify locally high or low strain values which may lead to bone resorption and thereby affect the clinical outcome. Using a finite element model the stresses and strains of a femur with all thigh muscle and joint contact forces were calculated for four phases of a gait cycle. Reduced load sets with only a few major muscles were analyzed alternatively. In a completely balanced femur with all thigh muscles the stress and strain patterns are characterized by combined bending and torsion throughout the bone. Similar to in vivo recordings, the model with all thigh muscles showed peak surface strains below 2000 mu epsilon (45% gait cycle). Under simplified load regimes surface strains reached values close to 3000 mu epsilon. Within the proximal femur, the simplified load regimes produced differences in strain as high as 26% in comparison to those with all thigh muscles included. This difference is reduced to 5% if the adductors are added to a loading consisting of hip contact, abductors and ilio-tibial band. This study demonstrates the importance of an ensemble of muscle forces to reproduce a physiological strain distribution in the femur. Analytical attempts to simulate bone modeling, remodeling or bone density distributions should therefore rely on fully balanced external load regimes which account for the role of the various soft tissue forces.

Biomechanical Phenomena↗
PubMed1998

A sensitive fluorescent assay for measuring the cysteine protease activity of Der p 1, a major allergen from the dust mite Dermatophagoides pteronyssinus.

The potent allergenicity of Der p 1, a major allergen of the house dust mite Dermatophagoides pteronyssinus, is thought to be related to its cysteine protease activity. Therefore, there is considerable interest in developing a sensitive assay for measuring Der p 1 activity to screen for specific inhibitors. This study demonstrates for the first time that the activity of Der p 1 can be measured conveniently in a continuous rate assay with the fluorogenic substrate Boc-Gln-Ala-Arg-AMC (K(m) = 280 microM and kcat/K(m) = 4.6 x 10(3)/M/s).

Allergens↗
PubMed1997

Dopamine receptor gene expression in an animal model of 'behavioral dependence' on ethanol.

The steady-state levels of messenger RNA (mRNA) of five cloned dopamine (D) receptors were measured in five brain regions in rats in a recently developed animal model of 'behavioral dependence' on ethanol. One group of rats was given the choice between ethanol and water over a 9-month period and developed 'behavioral dependence' on ethanol (group a). This group was compared with a group given the choice between ethanol and water for only 2 months (not yet behaviorally dependent, group b), a group forced to consume ethanol as sole fluid over a 9-month period (not behaviorally dependent, group c) and ethanol-naive control rats. All groups were sacrificed 1 month after ethanol withdrawal. The concentrations of mRNA of D3-receptors in the limbic forebrain (which included the nucleus accumbens) were significantly lowered in groups a and b, but unchanged in group c. D3 mRNA levels were reduced in the hippocampus of group b and unchanged in the cortex, amygdala and striatum. No significant changes in the mRNA concentrations of D1-, D2-, D4- or D5-receptors were seen in the five brain regions in any group. In conclusion, chronic consumption of ethanol under the 'free-choice condition', which may best induce the drug-rewarding effect, leads to specific changes in the D3-receptor gene expression which were not seen after forced ethanol administration. Changes in D3 mRNA levels were, however, not a specific correlate of 'behavioral dependence', as they were also detected in rats not yet 'behaviorally dependent' (group b).

Alcohol Drinking↗
PubMed1997

Cleavage of the low-affinity receptor for human IgE (CD23) by a mite cysteine protease: nature of the cleaved fragment in relation to the structure and function of CD23.

Der p I, a cysteine protease representing a major allergen of the house dust mite Dermatophagoides pteronyssinus, has recently been shown to cleave CD23 from the surface of cultured human B cells (RPMI 8866 B cell line). We have now undertaken a detailed investigation of CD23 cleavage by Der p I. We demonstrate that Der p I cleaves CD23 at two sites (Ser155-Ser156 and Glu298-Ser299) to produce a 17-kDa fragment containing the lectin domain and only part of the C-terminal tail. No such effect was demonstrable with mouse CD23, a finding which was anticipated based on its lack of the cleavage sites identified on human CD23. Based on the cleavage pattern and the model of CD23, we propose a sequence of events leading to the liberation of the 17-kDa soluble CD23 fragment. The biological significance of such cleavage is underlined by the demonstration that Der p I-treated B lymphocytes lose their ability to bind IgE, and that the 17-kDa fragment (amino acids 156-298) contains the minimum structural requirement (amino acids 156-288) for binding to both IgE and CD21.

Animals↗
PubMed1996

Contribution to the mechanism of chromate nephrotoxicity in developing rats: EPR investigations.

The effect of 2 mg and 1 mg Na2Cr2O7 (Cr)/100 g body wt. on renal function was investigated in 10- and 55-day-old rats, respectively. These doses were followed by equal Cr concentrations in the renal tissue of both age groups. Confirming previous data we found lower nephrotoxicity in young than in adult rats. The concentration of glutathione (GSH) and the activity of glutathione reductase (GSSG reductase) in renal tissue of adult rats were diminished by buthionine sulfoximine (BSO) and lomustine (CCNU) administration, respectively. In these animals Cr nephrotoxicity was decreased significantly. Lower nephrotoxicity was accompanied by slower disappearance of Cr(VI) from renal tissue homogenate in vitro. The time course of Cr(VI) reduction demonstrated by the signal intensity of Cr(V), as recorded by electron spin resonance (EPR) spectroscopy in the supernatant of renal tissue homogenate, enabled us to follow the reduction of Cr(VI) to Cr(III) via Cr(V). Maximally reached Cr(V) concentrations lowest in young rats, did not differ significantly in adult control and BSO and BSO + CCNU treated rats. Further reduction of Cr(V) to Cr(III) which appeared most rapidly in adult rats, was delayed by pretreatment with BSO and CCNU. From our results we concluded that (1) reduction of Cr(VI) was more related to the concentration of GSH than to the activity of GSSG reductase, (2) the formation of Cr-GSH-complexes with GSH oxidation seemed to be the first step of Cr(VI) metabolism, and (3) the stabilization of reactive Cr(V) by GSH seemed to be decisive for the preventive effect of BSO and CCNU as well as for age differences in chromate nephrotoxicity.

Age Factors↗
PubMed1996

Riboflavin can decrease the nephrotoxic effect of chromate in young and adult rats.

The influence of 5 mg vitamin B2/100 g b.wt. (B2, riboflavin) on the nephrotoxic effect of 1 or 2 mg Na2Cr2O7/100 g b.wt. (Cr) was investigated in 55- and 10-day-old rats, respectively. Nephrotoxic effect was evaluated by the determination of urinary volume and protein excretion as well as the concentration of blood urea nitrogen (BUN). The concomitant administration of Cr and B2 only in 55-day-old rats increased the nephrotoxicity shown by enhanced proteinuria and BUN. B2, administered 3 h after Cr, was able to diminish Cr nephrotoxicity significantly in 55- and 10-day-old rats. The effect of B2 on Cr nephrotoxicity could be interpreted not by the stimulatory effect of B2 on GSSG reductase, which was abolished by Cr; but by its antioxidant effect.

Age Factors↗
PubMed1995

Der p I, a major allergen of the house dust mite, proteolytically cleaves the low-affinity receptor for human IgE (CD23).

The nature of the proteases that cleave CD23 in vivo is of considerable interest, but remains unknown. Here, we demonstrate that Der p I, a major allergen of the house dust mite Dermatophagoides pteronyssinus, cleaves CD23 from the surface of cultured human B cells (RPMI 8866 B cell line). The cleavage of the receptor from the B cell surface was associated with a parallel increase in soluble CD23 (sCD23) in the culture supernatant. Furthermore, the proteolytic effect of Der p I was specific for CD23, since none of the other B cell markers tested (CD20, HLA-DR, CD71 and CD49d) were affected. Labeled antibody experiments and protease inhibition assays clearly demonstrate that Der p I is a cysteine protease that directly cleaves a 25-kDa fragment of CD23. These data suggest that the cysteine protease Der p I, in addition to being highly immunogenic, may up-regulate IgE synthesis by virtue of its ability to cleave CD23.

Allergens↗
PubMed1995

Two strategies to prepare neural cortical cytoskeleton components for the generation of monoclonal antibodies.

Like most other cells, neurons possess a spectrin/actin based network closely associated with the inner side of the cell membrane, the cortical cytoskeleton. This structure serves many diverse functions during axonal outgrowth. In the growth cone, the cortical cytoskeleton is involved in surface shaping, modulation of integral membrane proteins, and signal transduction. We developed two strategies to prepare material enriched for neural cortical cytoskeleton. The first strategy combined the isolation of a membrane/cortical cytoskeleton fraction by density gradient centrifugation with an enzymatic degradation of cell surface proteins. The second strategy is based on the attachment and crosslinking of single cells to beads, allowing for the removal of the cell contents by cell disruption; only membrane/cortical cytoskeleton patches are retained on the beads. Both strategies made use of the intimate association of the cortical cytoskeleton with the cell membrane, permitting the removal of cytoplasm, organelles and cytoplasmic cytoskeleton while retaining the cortical cytoskeleton. Monoclonal antibodies generated using both preparations as immunization material were screened for recognition of intracellular structures in axons and growth cones of retinal ganglion cells in culture. A quantitative specification of the antibodies is presented and six antibodies are characterized in immunolabelings and Western blot analysis.

Animals↗
PubMed1991

[Interrelationships between methylmercury exposure and selenium supplementation in cockerels using selected laboratory diagnostic parameters and toxicological parameters of residues].

A feed loading experiment was applied in 2 phases to 45 young cocks over 12 weeks, using 1,2-N,N-bis(methylmercury)-p-toluolsulphamide-dressed wheat (50% of base ration). Investigations were conducted to study the effects of selenium supplementation (0,2 mg Se as sodium selenite/l drinking water) on biochemical and hematological parameters (calcium, phosphorus, total protein, albumin, creatinine, urea, activity of alkaline phosphatase, hematocrit, hemoglobin, leucocyte count) as well as on parameters relating to toxicological residues (selenium and mercury levels in liver, musculature and kidneys). Statistically secured differences were found to exist between the experimental groups with regard to selenium and mercury in the liver and mercury concentrations in kidneys. Possible interrelationships were discussed.

Animals↗
PubMed1989

[Experimental laboratory diagnostic and residual toxicological studies in young cocks after feeding mercury-disinfected seed with and without selenium supplementation].

A feed loading experiment was applied in 2 phases to 45 young cocks over 12 weeks, using 1.2 (N, N-bis/methylmercury/-p-toluolsulphamide)-dressed wheat (50% of base ration). The experimental animals were White-Leghorn laying hybrids. Investigations were conducted to study the effects of exclusive exposure to mercury and those of mercury with addition of 0.2 mg of sodium selenite/l drinking water on biochemical parameters (calcium, phosphorus, total protein, albumin, creatinine, urea, activity of alkaline phosphatase, hematocrit, hemoglobin, and leucocyte count) as well as on parameters relating to toxicological residues (selenium and mercury levels in liver, musculature, and kidneys). Statistically secured differences were found to exist between the experimental groups with regard to selenium and mercury in the liver and mercury concentrations in kidneys. These data have shown that the problem of residualisation cannot be solved by selenium supplementation in parallel to methylmercury loading. The results recorded are likely to confirm the need for a general ban on feeding mercury-dressed seed.

Animal Feed↗