Biomedical subjects

R Schnabel

Publications and source records attributed to R Schnabel.

At least 19 recordsLinked to original sources

PubMed2007

Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study.

BACKGROUND: Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process. OBJECTIVES: To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis. PATIENTS/METHODS: Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UFH before blood drawing were excluded from the analyses on f-TFPI (n = 226). RESULTS: On admission, no significant differences in sTF levels were observed between SAP and ACS patients. By comparison to patients with stable angina, f-TFPI levels significantly increased in patients with acute unstable angina and further increased in patients presenting with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary artery disease, 56 died from a cardiovascular cause. In prospective analyses, high sTF levels were independently associated with an increased risk of cardiovascular death in individuals with ACS (fully adjusted hazard ratio associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45; P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were not independently associated with an increased risk of cardiovascular death. CONCLUSIONS: Plasma sTF levels were predictive of cardiovascular mortality in individuals with ACS, whereas f-TFPI levels were associated with the severity of myocardial damage on admission but were not independently related to outcome.

Aged↗

PubMed2006

Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study.

OBJECTIVE: To get a better insight into the role of hemostasis in coronary artery disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen, thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP) complexes on the risk of cardiovascular event in a prospective cohort of CAD patients. METHODS AND RESULTS: The prospective Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline. After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death, but not of nonfatal event. Except for vWF, these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF, fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model, fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI) associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to 1.55) and 1.29 (1.09 to 1.53), respectively. CONCLUSIONS: In patients with coronary artery disease, fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

Aged↗

PubMed2006

Demonstration of three-port grating phase relations.

We experimentally demonstrate the phase relations of three-port gratings by investigating three-port coupled Fabry-Perot cavities. Two different gratings that have the same first-order diffraction efficiency but differ substantially in their second-order diffraction efficiency have been designed and manufactured. Using the gratings as couplers to Fabry-Perot cavities, we could validate the results of an earlier theoretical description of the phases at a three-port grating [Opt. Lett. 30, 1183 (2005)].

Journal Article↗

PubMed2006

Optical characterization of ultrahigh diffraction efficiency gratings.

We report on the optical characterization of an ultrahigh diffraction efficiency grating in a first-order Littrow configuration. The apparatus used was an optical cavity built from the grating under investigation and an additional high-reflection mirror. The measurement of the cavity finesse provided precise information about the grating's diffraction efficiency and its optical loss. We measured a finesse of 1580 from which we deduced a diffraction efficiency of (99.635+/-0.016)% and an overall optical loss due to scattering and absorption of just 0.185%. Such high-quality gratings, including the tool used for their characterization, might apply for future gravitational wave detectors. For example, the demonstrated cavity itself presents an all-reflective, low-loss Fabry-Perot resonator that might replace conventional arm cavities in advanced high-power Michelson interferometers.

Journal Article↗

PubMed2006

Three-port beam splitters-combiners for interferometer applications.

We derive generic phase and amplitude coupling relations for beam splitters-combiners that couple a single port with three output ports or input ports, respectively. We apply the coupling relations to a reflection grating that serves as a coupler to a single-ended Fabry-Perot ring cavity. In the impedance-matched case such an interferometer can act as an all-reflective ring mode cleaner. It is further shown that in the highly undercoupled case almost complete separation of carrier power and phase signal from a cavity strain can be achieved.

Journal Article↗

PubMed2006

Comparative mapping of bovine chromosome 27 with human chromosome 8 near a dairy form QTL in cattle.

In the absence of a complete and annotated bovine genome sequence, detailed human-bovine comparative maps are one of the most effective tools for identification of positional candidate genes contributing to quantitative trait loci (QTL) in cattle. In the present study, eight genes from human chromosome 8 were selected for mapping in cattle to improve breakpoint resolution and confirm gene order on the comparative map near the 40 cM region of the BTA27 linkage map where a QTL affecting dairy form had previously been identified. The resulting map identified ADRB3 as a positional candidate gene for the QTL contributing to the dairy form trait based on its estimated position between 40 and 45 cM on the linkage map. It is also a functional candidate gene due to its role in fat metabolism, and polymorphisms in the ADRB3 gene associated with obesity and metabolic disease in humans, as well as, carcass fat in sheep. Further studies are underway to investigate the existence of polymorphisms in the bovine ADRB3 gene and their association with traits related to fat deposition in cattle.

Animals↗

PubMed2005

Input-output relations for a three-port grating coupled Fabry-Perot cavity.

We analyze an optical three-port reflection grating by means of a scattering matrix formalism. Amplitude and phase relations among the three ports, i.e., the three orders of diffraction, are derived. Such a grating can be used as an all-reflective, low-loss coupler to Fabry-Perot cavities. We derive the input-output relations of a three-port grating coupled cavity and find distinct properties that are not present in two-port coupled cavities. The cavity relations further reveal that the three-port coupler can be designed such that the additional cavity port interferes destructively. In this case the all-reflective, low-loss, single-end Fabry-Perot cavity becomes equivalent to a standard transmissive, two-port coupled cavity.

Journal Article↗

PubMed2004

Low-loss grating for coupling to a high-finesse cavity.

A concept for a low-loss all-reflective cavity coupler is experimentally demonstrated at a wavelength of 1064 nm. A 1450-nm period dielectric reflection grating with a diffraction efficiency of 0.58% in the - 1st order is used in the 2nd-order Littrow configuration as a coupler to form a cavity with a finesse of 400. The application of such reflective low-loss cavity couplers in future generations of gravitational-wave detectors and implementation issues are discussed.

Journal Article↗

PubMed2003

Experimental investigation of criteria for continuous variable entanglement.

We generate a pair of entangled beams from the interference of two amplitude squeezed beams. The entanglement is quantified in terms of EPR paradox and inseparability criteria, with both results clearly beating the standard quantum limit. We experimentally analyze the effect of decoherence on each criterion and demonstrate qualitative differences. We also characterize the number of required and excess photons present in the entangled beams and provide contour plots of the efficacy of quantum information protocols in terms of these variables.

Journal Article↗

PubMed2003

[Primary adenocarcinoma of the left atrium mimicking benign myxoma].

Primary tumors of the heart are rare, whereas cardiac metastases, most frequently from adenocarcinomas, occur in up to 20% of malignant tumors. We report about a 61-year-old female patient who was admitted with recurrent stress-induced dizziness, intermittent tachycardia and a fall due to a pre-syncope. Echocardiography showed a left atrial tumor with the typical features of a pediculated myxoma, leading to open heart surgery. However, histopathology revealed a 2.2 x 1.5 cm adenocarcinoma. The subsequent search for a primary tumor, including tumor markers and (18)F-FDG-PET, was unsuccessful, as was a second thorough diagnostic workup half a year later. The tumor was therefore classified as a primary cardiac adenocarcinoma.

Adenocarcinoma↗

PubMed2003

Mother's voice "buffers" separation-induced receptor changes in the prefrontal cortex of octodon degus.

Although the potential vulnerability of the postnatally developing brain toward adverse environmental influences is generally recognized, relatively little is known about the basic mechanisms involved. The plasticity and adaptability of the postnatally developing brain in response to adverse emotional experiences was analyzed in the South American Octodon degus. Our study revealed that repeated brief separation from the parents and exposure to an unfamiliar environment induces an up-regulation of dopamine (D1) and 5-hydroxytrytamine (5HT1(A))-receptor density in the precentral medial, anterior cingulate, prelimbic and infralimbic cortices in female pups. No significant changes of gamma aminobutyric acid (GABA(A)) receptor density were found in deprived animals of both genders. The acoustic presence of the mother during parental separation suppressed the D1-receptor up-regulation as well as the 5-HT1(A)-receptor up-regulation, again only in the female pups. These results demonstrate that that early adverse emotional experience alters aminergic function within the prefrontal cortex in the female but not the male brain. The mother's voice, a powerful emotional signal, can protect the developing cortex from separation-induced receptor changes.

Acoustic Stimulation↗

PubMed2002

Effect of nitric oxide in ischemia/reperfusion of the pancreas.

BACKGROUND: Ischemia/reperfusion injury, and thus graft pancreatitis, remains a major problem in pancreas transplantation. Contradictory results about the role of nitric oxide (NO) in pancreatic ischemia/reperfusion have been reported; however, in none of the reports has a detailed comparison between inhibition of NO synthase and NO supplementation been carried out. METHODS: Vascular isolation of the pancreatic tail was performed in landrace pigs. After splenectomy catheters placed in the distal part of the splenic vessels allowed collection of the venous effluent and perfusion of the pancreatic tail. Three hours of complete warm ischemia was followed by 6 h of reperfusion. The effect of the NO donor sodium nitroprusside (SNP) and L-arginine was compared to a control group and NO synthase inhibition with L-NAME. RESULTS: Lipase in the venous effluent of the pancreas was significantly decreased in the SNP and the L-arginine groups. Vascular resistance was markedly elevated in the L-NAME group and reduced in the NO donor groups. Tissue pO2 after reperfusion was only significantly elevated in the SNP group. Granulocyte infiltration and also overall histological tissue injury were most severe in the control group followed by the L-NAME group, the SNP group, and the L-ARG group. CONCLUSION: The data show that supplementation of nitric oxide is clearly protective in pancreatic ischemia/reperfusion. However, inhibition of NO synthesis does not lead to an equally clear aggravation of tissue injury.

Acute Disease↗

PubMed2002

Hydrogen peroxide-mediated killing of Caenorhabditis elegans by Streptococcus pyogenes.

Caenorhabditis elegans is currently introduced as a new, facile, and cheap model organism to study the pathogenesis of gram-negative bacteria such as Pseudomonas aeruginosa and Salmonella enterica serovar Typhimurium. The mechanisms of killing involve either diffusible exotoxins or infection-like processes. Recently, it was shown that also some gram-positive bacteria kill C. elegans, although the precise mechanisms of killing remained open. We examined C. elegans as a pathogenesis model for the gram-positive bacterium Streptococcus pyogenes, a major human pathogen capable of causing a wide spectrum of diseases. We demonstrate that S. pyogenes kills C. elegans, both on solid and in liquid medium. Unlike P. aeruginosa and S. enterica serovar Typhimurium, the killing by S. pyogenes is solely mediated by hydrogen peroxide. Killing required live streptococci; the killing capacity depends on the amount of hydrogen peroxide produced, and killing can be inhibited by catalase. Major exotoxins of S. pyogenes are not involved in the killing process as confirmed by using specific toxin inhibitors and knockout mutants. Moreover, no accumulation of S. pyogenes in C. elegans is observed, which excludes the involvement of infection-like processes. Preliminary results show that S. pneumoniae can also kill C. elegans by hydrogen peroxide production. Hydrogen peroxide-mediated killing might represent a common mechanism by which gram-positive, catalase-negative pathogens kill C. elegans.

Animals↗

PubMed2001

Engulfment genes cooperate with ced-3 to promote cell death in Caenorhabditis elegans.

Genetic studies have identified over a dozen genes that function in programmed cell death (apoptosis) in the nematode Caenorhabditis elegans. Although the ultimate effects on cell survival or engulfment of mutations in each cell death gene have been extensively described, much less is known about how these mutations affect the kinetics of death and engulfment, or the interactions between these two processes. We have used four-dimensional-Nomarski time-lapse video microscopy to follow in detail how cell death genes regulate the extent and kinetics of apoptotic cell death and removal in the early C. elegans embryo. Here we show that blocking engulfment enhances cell survival when cells are subjected to weak pro-apoptotic signals. Thus, genes that mediate corpse removal can also function to actively kill cells.

ATP-Binding Cassette Transporters↗

PubMed2001

Essential roles for four cytoplasmic intermediate filament proteins in Caenorhabditis elegans development.

The structural proteins of the cytoplasmic intermediate filaments (IFs) arise in the nematode Caenorhabditis elegans from eight reported genes and an additional three genes now identified in the complete genome. With the use of double-stranded RNA interference (RNAi) for all 11 C. elegans genes encoding cytoplasmic IF proteins, we observe phenotypes for the five genes A1, A2, A3, B1, and C2. These range from embryonic lethality (B1) and embryonic/larval lethality (A3) to larval lethality (A1 and A2) and a mild dumpy phenotype of adults (C2). Phenotypes A2 and A3 involve displaced body muscles and paralysis. They probably arise by reduction of hypodermal IFs that participate in the transmission of force from the muscle cells to the cuticle. The B1 phenotype has multiple morphogenetic defects, and the A1 phenotype is arrested at the L1 stage. Thus, at least four IF genes are essential for C. elegans development. Their RNAi phenotypes are lethal defects due to silencing of single IF genes. In contrast to C. elegans, no IF genes have been identified in the complete Drosophila genome, posing the question of how Drosophila can compensate for the lack of these proteins, which are essential in mammals and C. elegans. We speculate that the lack of IF proteins in Drosophila can be viewed as cytoskeletal alteration in which, for instance, stable microtubules, often arranged as bundles, substitute for cytoplasmic IFs.

Animals↗

PubMed2001

Membrane insertion of the heptameric staphylococcal alpha-toxin pore. A domino-like structural transition that is allosterically modulated by the target cell membrane.

Staphylococcal alpha-toxin forms heptameric pores on eukaryotic cells. After binding to the cell membrane in its monomeric form, the toxin first assembles into a heptameric pre-pore. Subsequently, the pre-pore transforms into the final pore by membrane insertion of an amphipathic beta-barrel, which comprises the "central loop" domains of all heptamer subunits. The process of membrane insertion was analyzed here using a set of functionally altered toxin mutants. The results show that insertion may be initiated within an individual protomer when its NH2 terminus activates its central loop. The activated state is then shared with the central loops of the residual heptamer subunits, which results in cooperative membrane penetration. This cooperation of the central loops commences while these are still remote from the lipid bilayer. Nevertheless, it is subject to modulation by the target membrane, which therefore acts across a distance much like an allosteric effector. However, while allosteric transitions usually are reversible, membrane insertion of alpha-toxin is an irreversible event, and we show here that it can proceed to completion in a domino-like fashion when triggered by as little as a single foreign atom within the entire heptamer.

Allosteric Regulation↗

PubMed2001

Protein phosphatase inhibitors facilitate DHPG-induced LTD in the CA1 region of the hippocampus.

We have shown earlier that activation of metabotropic glutamate (mGlu) receptors using a group I-specific mGlu receptor agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), can induce long-term depression (LTD) in the CA1 region of the hippocampus. In an attempt to determine the signal transduction mechanisms involved in this form of synaptic plasticity, we have tested the effects of a range of inhibitors on DHPG-induced LTD. In vitro grease-gap electrophysiological recordings were performed in the rat hippocampal CA1 region. We have found that DHPG-induced LTD is resistant to the two potent protein kinase C (PKC) inhibitors, Gö 6976 (10 microM) and Gö 6983 (10 microM), the potent and selective protein kinase A (PKA) inhibitor, KT 5720 (10 microM), and the potent broad spectrum kinase inhibitor, staurosporine (10 microM). In contrast, non-selective inhibitors of protein phosphatases (PP1 and PP2A), okadaic acid (1 microM) or calyculin A (1 microM), facilitated DHPG-induced LTD. However, an inhibitor of protein phosphatase 2B, FK 506 (1 microM), did not influence this process. The PP1/PP2A protein phosphatase inhibitors, but none of the other agents tested, also inhibited (S)-alpha-methyl-4-carboxyphenylglycine (MCPG)-induced reversal of DHPG-induced LTD. These data suggest that activation of neither PKC nor PKA is involved in DHPG-induced LTD. They do, however, suggest that the process is under regulation by protein phosphorylation and dephosphorylation.

Animals↗

PubMed2001

Partial liquid ventilation in severely surfactant-depleted, spontaneously breathing rabbits supported by proportional assist ventilation.

OBJECTIVE: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV). This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. DESIGN: Randomized trial. SETTING: University animal research facility. SUBJECTS: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- sd). INTERVENTIONS: After pulmonary lavage (target Pao2 <100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an Fio2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV. PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao2, Paco2, tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, heart rate, pulmonary compliance, and airway resistance were measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. MAIN RESULTS: Pao2 and compliance were significantly higher in PLV rabbits compared with controls (p <.05, analysis of variance for repeated measures). All other parameters were similar in both groups. CONCLUSIONS: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.

Analysis of Variance↗