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Biomedical subjects

A Suter

Publications and source records attributed to A Suter.

At least 19 recordsLinked to original sources
PubMed2006

Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system.

Echinacea is a widely used herbal remedy for the prevention and treatment of the common cold. Recently, many new insights concerning the molecular mode of action of the main lipophilic constituents, the alkamides, have renewed interest in this plant. In order to compare the bioavailability of alkamides from liquid and tablet preparations of E. purpurea (Echinaforce) in humans and to study the effects on ex vivo stimulated blood cells, a randomized, single-dose, crossover study with 10 (8 test, 2 placebo) volunteers has been performed. They received either 4 ml of the standardized E. purpurea (Echinaforce) tincture or 12 E. purpurea (Echinaforce) tablets or placebo. Both doses contained the same amount (0.07 mg) of the major alkamides, dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides. Liquid chromatography electrospray ionization ion-trap mass spectrometry was used to determine the content of alkamides in serum. It was found that the arithmetic mean C(max) of dodeca-2E,4E, 8Z,10E/Z-tetraenoic acid isobutylamides absorbed after oral application of the Echinaforce tincture appeared after 30 min (0.40 ng/ml serum). In comparison, the t(max) of tablets was 45 min with a C(max) of 0.12 ng/ml. An ex vivo stimulation of blood by LPS was carried out to measure the influence of E. purpurea on the innate and adaptive immune system. Both E. purpurea preparations led to the same effects on the immune system according to the concentration of pro-inflammatory cytokines TNF-alpha and IL-8. 23 hours after oral application a significant down-regulation of TNF-alpha and IL-8 in LPS pre-stimulated whole blood was found. However, no significant changes in the concentration of IL-6 were observed. Although a quarter of the dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides was absorbed from the tablets, the study shows that the formulations trigger the same effects on the measured immune parameters.

Adult↗
PubMed2005

Coexistence and coupling of superconductivity and magnetism in thin film structures.

Superconducting and magnetic order are usually mutually exclusive, and are found to coexist in relatively few materials. We have obtained direct evidence for a spin-density wave (SDW) coexisting with bulk superconductivity in a ferromagnetic-superconducting trilayer. In the superconducting state the amplitude of the SDW is enhanced and modeling the data also suggests a pi/2 phase shift of one component of the SDW, implying a profound coupling of these two forms of order.

Journal Article↗
PubMed2004

Direct observation of nonlocal effects in a superconductor.

We have used the technique of low energy muon spin rotation to measure the local magnetic field profile B(z) beneath the surface of a lead film maintained in the Meissner state (z depth from the surface, z less, similar 200 nm). The data unambiguously show that B(z) clearly deviates from an exponential law and represent the first direct, model independent proof for a nonlocal response in a superconductor.

Journal Article↗
PubMed2004

Direct observation of the oxygen isotope effect on the in-plane magnetic field penetration depth in optimally doped YBa2Cu3O7-delta.

We report the first direct observation of the oxygen-isotope ((16)O/(18)O) effect on the in-plane penetration depth lambda(ab) in a nearly optimally doped YBa(2)Cu(3)O(7-delta) film using the novel low-energy muon-spin rotation technique. Spin-polarized low-energy muons are implanted in the film at a known depth z beneath the surface and process in the local magnetic field B(z). This feature allows us to measure directly the profile B(z) of the magnetic field inside the superconducting film in the Meissner state and to make a straightforward determination of lambda(ab). A substantial isotope shift Delta lambda(ab)/lambda(ab)=2.8(1.0)% at 4 K is observed, implying that the in-plane effective supercarrier mass m*(ab) is oxygen-isotope dependent with Delta m*(ab)/m*(ab)=5.5(2.0)%. These results are in good agreement with magnetization measurements on powder samples.

Journal Article↗
PubMed2004

What patients want to know before they have cataract surgery.

AIMS: To investigate what patients want to know before undergoing cataract surgery. METHODS: A written questionnaire was answered by 190 patients prior to cataract surgery. RESULTS: The five pieces of preoperative information rated most important were: chance of visual improvement; when vision would improve; overall risk of losing vision from the operation; effect of not having the operation, and the types of serious complications. When asked "should you be warned of a serious complication if it has a risk of happening", 93.5% said yes to a risk of 1 in 50 and 62.4% to 1 in 1000. Written information was requested by 85.7%. There were few differences between the sexes, and between those having their first or second operation. CONCLUSIONS: Patients most wanted to know benefits and risks, even very small risks. Written information should be provided to ensure coverage and reinforce verbal information.

Aged↗
PubMed2003

Observation of the conduction electron spin polarization in the Ag spacer of a Fe/Fg/Fe trilayer.

The spatially oscillating electron spin polarization in the Ag spacer of a 4 nm Fe/20 nmAg/4 nm Fe(001) epitaxial trilayer has been determined by means of low energy muon spin rotation. It oscillates with the same period as the interlayer exchange coupling, but shows a much weaker attenuation at large distances x from the interface. The measured magnetization profile from the inner 14 nm of the spacer is described by an oscillating polarization decaying as x(-0.8(1)). This unusual behavior may arise from a full confinement of electron states within the spacer.

Journal Article↗
PubMed2003

A randomised double blind placebo controlled clinical trial of a standardised extract of fresh Crataegus berries (Crataegisan) in the treatment of patients with congestive heart failure NYHA II.

A placebo controlled, randomised, parallel group, multicentre trial conducted in accordance with the guidelines of Good Clinical Practice (GCP) shows the efficacy and safety of a standardised extract of fresh berries of Crataegus oxyacantha L. and monogyna Jacq. (Crataegisan) in patients with cardiac failure NYHA class II. A total of 143 patients (72 men, 71 women, mean age of 64.8 (8.0 years) were recruited and treated with 3 times 30 drops of the extract (n = 69) or placebo (n = 74) for 8 weeks. The primary variable for the evaluation of efficacy was the change in exercise tolerance determined with bicycle exercise testing, secondary variables included the blood pressure-heart rate product (BHP). Subjective cardiac symptoms at rest and at higher levels of exertion were assessed by the patient on a categorical rating scale. An overall assessment of efficacy at the final visit was provided by the patient and the investigator. In the ITT population there was a significant increase in exercise tolerance in both groups between visit 1 and visit 3. The difference between the treatment groups was 8.3 watts in favour of the standardised extract of fresh Crataegus berries (p = 0.045). The result is confirmed in the PP population (p = 0.047). Changes in BHP at 50 watts and at comparable maximum load were in favour of Crataegus extract but the results are not statistically significant. The subjective assessment of cardiac symptoms at rest and at higher levels of exertion did not change significantly and the patient and investigator overall assessment of efficacy were similar for the two groups. The medication was well tolerated and had a high level of patient acceptability. The significant improvement, due to the fact that dyspnoea and fatigue do not occur until a significantly higher wattage has been reached in the bicycle exercise testing allows the conclusion that the recruited NYHA II patients may expect an improvement in their heart failure condition under long term therapy with the standardised extract of fresh Crataegus berries.

Aged↗
PubMed2002

Probe--sample coupling in the magnetic resonance force microscope.

The magnetic resonance force microscope (MRFM) provides a route to achieving scanned probe magnetic resonance imaging with extremely high spatial resolution. Achieving this capability will require understanding the force exerted on a microscopic magnetic probe by a spatially extended sample over which the probe is scanned. Here we present a detailed analysis of this interaction between probe and sample. We focus on understanding the situation where the micromagnet mounted on the mechanical resonator generates a very inhomogeneous magnetic field and is scanned over a sample with at least one spatial dimension much larger than that of the micromagnet. This situation differs quite significantly from the conditions under which most MRFM experiments have been carried out where the sample is mounted on the mechanical resonator and placed in a rather weak magnetic field gradient. In addition to the concept of a sensitive slice (the spatial region where the magnetic resonance condition is met) it is valuable to map the forces exerted on the probe by spins at various locations; this leads to the concept of the force slice (the region in which spins exert force on the resonator). Results of this analysis, obtained both analytically and numerically, will be qualitatively compared with an initial experimental finding from an EPR-MRFM experiment carried out on DPPH at 4 K.

Journal Article↗
PubMed2001

Biosynthesis of phosphatidylcholine from a phosphocholine precursor pool derived from the late endosomal/lysosomal degradation of sphingomyelin.

Previous studies suggest that the steps of the CDP- choline pathway of phosphatidylcholine synthesis are tightly linked in a so-called metabolon. Evidence has been presented that only choline that enters cells through the choline transporter, and not phosphocholine administered to cells by membrane permeabilization, is incorporated into phosphatidylcholine. Here, we show that [(14)C]phosphocholine derived from the lysosomal degradation of [(14)C]choline-labeled sphingomyelin is incorporated as such into phosphatidylcholine in human and mouse fibroblasts. Low density lipoprotein receptor-mediated endocytosis was used to specifically direct [(14)C]sphingomyelin to the lysosomal degradation pathway. Free labeled choline was not found either intracellularly or in the medium, not even when the cells were energy-depleted. Deficiency of lysosomal acid phosphatases in mouse or alkaline phosphatase in human fibroblasts did not affect the incorporation of lysosomal [(14)C]sphingomyelin-derived [(14)C]phosphocholine into phosphatidylcholine, supporting our finding that phosphocholine is not degraded to choline prior to its incorporation into phosphatidylcholine. Inhibition studies and analysis of molecular species showed that exogenous [(3)H]choline and sphingomyelin-derived [(14)C]phosphocholine are incorporated into phosphatidylcholine via a common pathway of synthesis. Our findings provide evidence that, in fibroblasts, phosphocholine derived from sphingomyelin is transported out of the lysosome and subsequently incorporated into phosphatidylcholine without prior hydrolysis of phosphocholine to choline. The findings do not support the existence of a phosphatidylcholine synthesis metabolon in fibroblasts.

Alkaline Phosphatase↗
PubMed2001

Optimal cell source for cardiovascular tissue engineering: venous vs. aortic human myofibroblasts.

Arterial vascular cells have been successfully utilized for tissue engineering in human cardiovascular structures, such as heart valves. The present study evaluates saphenous vein-derived myofibroblasts as an alternative, easy-to-access cell source for human cardiovascular tissue engineering. Biodegradable polyurethane scaffolds were seeded with human vascular myofibroblasts. Group A consisted of scaffolds seeded with cells from ascending aortic tissue; in group B, saphenous vein-derived cells were used. Analysis included histology, electron microscopy, mechanical testing, and biochemical assays for cell proliferation (DNA) and extracellular matrix (collagen). DNA content was comparable in both groups. Collagen and stress at maximum load was significantly higher in group B. Morphology showed viable, layered cellular tissue in all samples, with collagen fibrils most pronounced in group B. In conclusion, saphenous vein myofibroblasts cultured on biodegradable scaffolds showed excellent in vitro tissue generation. Collagen formation and mechanical properties were superior to aortic tissue derived constructs. Therefore, the easy-to-access vein cells represent a promising alternative cell source for cardiovascular tissue engineering.

Aorta↗
PubMed2001

Overlapping functions of lysosomal acid phosphatase (LAP) and tartrate-resistant acid phosphatase (Acp5) revealed by doubly deficient mice.

To date, two lysosomal acid phosphatases are known to be expressed in cells of the monocyte/phagocyte lineage: the ubiquitously expressed lysosomal acid phosphatase (LAP) and the tartrate-resistant acid phosphatase-type 5 (Acp5). Deficiency of either acid phosphatase results in relatively mild phenotypes, suggesting that these enzymes may be capable of mutual complementation. This prompted us to generate LAP/Acp5 doubly deficient mice. LAP/Acp5 doubly deficient mice are viable and fertile but display marked alterations in soft and mineralised tissues. They are characterised by a progressive hepatosplenomegaly, gait disturbances and exaggerated foreshortening of long bones. Histologically, these animals are distinguished by an excessive lysosomal storage in macrophages of the liver, spleen, bone marrow, kidney and by altered growth plates. Microscopic analyses showed an accumulation of osteopontin adjacent to actively resorbing osteoclasts of Acp5- and LAP/Acp5-deficient mice. In osteoclasts of phosphatase-deficient mice, vacuoles were frequently found which contained fine filamentous material. The vacuoles in Acp5- and LAP/Acp5 doubly-deficient osteoclasts also contained crystallite-like features, as well as osteopontin, suggesting that Acp5 is important for processing of this protein. This is further supported by biochemical analyses that demonstrate strongly reduced dephosphorylation of osteopontin incubated with LAP/Acp5-deficient bone extracts. Fibroblasts derived from LAP/Acp5 deficient embryos were still able to dephosphorylate mannose 6-phosphate residues of endocytosed arylsulfatase A. We conclude that for several substrates LAP and Acp5 can substitute for each other and that these acid phosphatases are essential for processing of non-collagenous proteins, including osteopontin, by osteoclasts.

Acid Phosphatase↗
PubMed2000

Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice.

Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane. Here we show that LAMP-2 deficiency in mice increases mortality between 20 and 40 days of age. The surviving mice are fertile and have an almost normal life span. Ultrastructurally, there is extensive accumulation of autophagic vacuoles in many tissues including liver, pancreas, spleen, kidney and skeletal and heart muscle. In hepatocytes, the autophagic degradation of long-lived proteins is severely impaired. Cardiac myocytes are ultrastructurally abnormal and heart contractility is severely reduced. These findings indicate that LAMP-2 is critical for autophagy. This theory is further substantiated by the finding that human LAMP-2 deficiency causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes.

Amino Acids↗
PubMed2000

Charge degree of freedom and the single-spin fluid model in YBa2Cu4O8

We present a 17O nuclear magnetic resonance study in the stoichiometric superconductor YBa2Cu4O8. A double irradiation method enables us to show that, below around 200 K, the spin-lattice relaxation rate of plane oxygen is not only driven by magnetic fluctuations, but also significantly by quadrupolar fluctuations, i. e., low-frequency charge fluctuations. In the superconducting state, on lowering the temperature, the quadrupolar relaxation diminishes faster than the magnetic one. These findings show that, with the opening of the spin pseudogap, a charge degree of freedom of mainly oxygen character is present in the electronic low-energy excitation spectrum.

Journal Article↗
PubMed2000

Suppression and recovery of adrenal response after short-term, high-dose glucocorticoid treatment.

BACKGROUND: Suppression of the adrenal response is an unpredictable consequence of glucocorticoid treatment. To investigate the kinetics of the adrenal response after short-term, high-dose glucocorticoid treatment, we measured the adrenal response to the low-dose (1 microg) corticotropin stimulation test. METHODS: We studied 75 patients who received the equivalent of at least 25 mg prednisone daily for between 5 days and 30 days. After discontinuation of glucocorticoid treatment, 1 microg corticotropin was administered intravenously, and stimulated plasma cortisol concentrations were measured 30 min later. In patients with a suppressed response to 1 microg corticotropin, the test was repeated until stimulated plasma cortisol concentrations reached the normal range. FINDINGS: The adrenal response to 1 microg corticotropin was suppressed in 34 patients and normal in 41. Subsequent low-dose corticotropin tests showed a steady recovery of the adrenal response within 14 days. In two patients, the adrenal response remained suppressed for several months. There was no correlation between plasma cortisol concentrations and the duration or dose of glucocorticoid treatment. INTERPRETATION: Suppression of the adrenal response is common after short-term, high-dose glucocorticoid treatment. The low-dose corticotropin test is a sensitive and simple test to assess the adrenal response after such treatment.

Adrenal Glands↗
PubMed2000

Separation of quadrupolar and magnetic contributions to spin-lattice relaxation in the case of a single isotope

We present a NMR pulse double-irradiation method which allows one to separate magnetic from quadrupolar contributions in the spin-lattice relaxation. The pulse sequence fully saturates one transition while another is observed. In the presence of a ||Deltam || = 2 quadrupolar contribution, the intensity of the observed line is altered compared to a standard spin-echo experiment. We calculated analytically this intensity change for spins I = 1, 32, 52, thus providing a quantitative analysis of the experimental results. Since the pulse sequence we used takes care of the absorbed radiofrequency power, no problems due to heating arise. The method is especially suited when only one NMR sensitive isotope is available. Different cross-checks were performed to prove the reliability of the results obtained. The applicability of this method is demonstrated by a study of the plane oxygen (17)O (I = 52) in the high-temperature superconductor YBa(2)Cu(4)O(8): the (17)O spin-lattice relaxation rate consists of magnetic as well as quadrupolar contributions. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Functions of cathepsin K in bone resorption. Lessons from cathepsin K deficient mice.

Cathepsin K is a cysteine proteinase expressed predominantly in osteoclasts. Cathepsin K cleaves key bone matrix proteins and is believed to play an important role in degrading the organic phase of bone during bone resorption. Pycnodysostosis, an autosomal recessive osteosclerosing skeletal disorder has recently been shown to result from mutations in the cathepsin K gene. Cathepsin K deficient mice generated by targeted disruption of this proteinase phenocopy many aspects of pycnodysostosis. They display an osteopetrotic phenotype with excessive trabeculation of the bone-marrow space accompanied by an altered ultrastructural appearance of the cathepsin K deficient osteoclasts. These cells also demonstrate an impaired resorptive activity in vitro. In contrast to other forms of osteopetrosis, which are due to disrupted osteoclastogenesis, cathepsin K deficiency is associated with an inhibition of osteoclast activity. Taken together the phenotype of cathepsin K knockout mice underlines the importance of this proteinase in bone remodelling.

Animals↗
PubMed1994

[Lengthening, axial correction and segmental reconstruction of the extremities using the distraction method].

Between 1988 and 1992 lengthenings axial, corrections and reconstructions have been performed by distraction on lower arms, upper and lower legs in 25 patients because of deviations in length due to either congenital or acquired (multiple cartilaginous exostoses, posttraumatic conditions, congenital pseudarthrosis deformations or defects (fibula-defect, amnion-band-complex, amputation). On the average elongation amounted to 4 cm for an average installation time of the fixator system of 22 weeks and a mean duration of 25 weeks for the adaptation to full strength. Problems arose in the form of soft tissue infections at the rod perforation sites, the necessity for secondary interventions because of early fractures and for corrections of the fixator respectively. Complications compromising the expected goal of treatment did not occur. Consideration of the biological principle of distraction is essential whereas the type of fixator-system is of only minor importance.

Adolescent↗