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1.
Prenat Diagn ; 44(8): 988-995, 2024 07.
Article in English | MEDLINE | ID: mdl-38797992

ABSTRACT

OBJECTIVE: We aim to provide a template structured report of fetal Magnetic Resonance Imaging in congenital diaphragmatic hernia (CDH) that was locally validated by the CDH study group in Mannheim. METHODS: A selection of 50 fetal MRIs of patients with an isolated diaphragmatic hernia and associated radiology reports from five different senior radiologists from a single center resulted in a primary structured report, which was put into practice by using dedicated software. A questionnaire survey of the interdisciplinary CDH study group Mannheim was used to adapt the report to the clinical requirements. RESULTS: There was a huge variability in how deep the free text reports go into detail. The side of the hernia was named in 94% of cases. In 58%, both the lung volume and the total lung volume were reported. A comparison with the expected lung volume was reported in 66% of cases. Additional findings, such as herniated organs, were reported in 96% of cases. Overall satisfaction with the newly established structured report was high within the CDH study group with a mean of 4.7. CONCLUSIONS: The use of the structured report of this study can optimize the interdisciplinary dialog, the standardization of report content, increase report completeness and improve quality.


Subject(s)
Hernias, Diaphragmatic, Congenital , Magnetic Resonance Imaging , Humans , Hernias, Diaphragmatic, Congenital/diagnostic imaging , Magnetic Resonance Imaging/methods , Female , Pregnancy , Prenatal Diagnosis/methods , Surveys and Questionnaires
2.
Phys Rev Lett ; 128(25): 255001, 2022 Jun 24.
Article in English | MEDLINE | ID: mdl-35802445

ABSTRACT

The magneto-Rayleigh-Taylor instability (MRTI) plays an essential role in astrophysical systems and in magneto-inertial fusion, where it is known to be an important degradation mechanism of confinement and target performance. In this Letter, we show for the first time experimental evidence of mode mixing and the onset of an inverse-cascade process resulting from the nonlinear coupling of two discrete preseeded axial modes (400- and 550-µm wavelengths) on an Al liner that is magnetically imploded using the 20-MA, 100-ns rise-time Z Machine at Sandia National Laboratories. Four radiographs captured the temporal evolution of the MRTI. We introduce a novel unfold technique to analyze the experimental radiographs and compare the results to simulations and to a weakly nonlinear model. We find good quantitative agreement with simulations using the radiation magnetohydrodynamics code hydra. Spectral analysis of the MRTI time evolution obtained from the simulations shows evidence of harmonic generation, mode coupling, and the onset of an inverse-cascade process. The experiments provide a benchmark for future work on the MRTI and motivate the development of new analytical theories to better understand this instability.

3.
Anaesthesist ; 70(3): 204-212, 2021 Mar.
Article in German | MEDLINE | ID: mdl-33001236

ABSTRACT

BACKGROUND: Levosimendan is a cardiac inotrope that augments myocardial contractility without increasing myocyte oxygen consumption. Additionally, levosimendan has been shown to exhibit anti-inflammatory, antioxidative, and other cardioprotective properties and is approved for treatment of heart failure. Recent studies indicated that these beneficial effects can be achieved with doses lower than the standard dose of 12.5 mg. Patients with preoperatively diagnosed left ventricular ejection fraction (LVEF) ≤40% received 1.25 mg levosimendan after induction of anesthesia. After surgery, administration of low-dose levosimendan was repeated until cardiovascular stability was achieved. OBJECTIVE: This study aimed to evaluate if pharmacological preconditioning with 1.25 mg levosimendan in patients with LVEF ≤40% altered the postoperative need for inotropic agents, the incidence of newly occurring atrial fibrillation, renal replacement therapy, mechanical circulatory support and 30-day mortality. The cumulative dosage of levosimendan was recorded to assess the required dosage in the context of individualized treatment. MATERIAL AND METHODS: This retrospective study included patients with preoperatively diagnosed LVEF ≤40% who underwent cardiac surgery at this institution between January 2015 and December 2018 and who received 1.25 mg levosimendan after induction of anesthesia to prevent postoperative low cardiac output syndrome. Based on echocardiography results, invasive hemodynamic monitoring, and central venous or mixed venous oxygen saturation and lactate clearance, repetitive doses of levosimendan in 1.25 mg increments could be postoperatively administered until cardiovascular stability was achieved. The results were compared to the current literature. RESULTS: We identified 183 patients with LVEF <40% who received pharmacological preconditioning with 1.25 mg levosimendan. Maximum doses of epinephrine, incidence of atrial fibrillation, need for renal replacement therapy and 30-day mortality were found to be below the published rates of comparable patient collectives. In 73.2% of patients, a cumulative dosage of 5 mg levosimendan or less was considered sufficient. CONCLUSION: The presented concept of pharmacological preconditioning with 1.25 mg levosimendan followed by individualized additional dosing in cardiac surgery patients with preoperative LVEF ≤40% suggests that this concept is safe, with possible advantages regarding the need of inotropic agents, renal replacement therapy, and 30-day mortality, compared to the current literature. Individualized treatment with levosimendan to support hemodynamics and a timely reduction of inotropic agents needs further confirmation in randomized trials.


Subject(s)
Cardiac Surgical Procedures , Pyridazines , Cardiac Output, Low/drug therapy , Cardiac Output, Low/prevention & control , Cardiotonic Agents/therapeutic use , Humans , Hydrazones/therapeutic use , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Pyridazines/therapeutic use , Retrospective Studies , Simendan/pharmacology , Stroke Volume , Ventricular Function, Left
4.
Phys Rev Lett ; 125(15): 155002, 2020 Oct 09.
Article in English | MEDLINE | ID: mdl-33095639

ABSTRACT

We present experimental results from the first systematic study of performance scaling with drive parameters for a magnetoinertial fusion concept. In magnetized liner inertial fusion experiments, the burn-averaged ion temperature doubles to 3.1 keV and the primary deuterium-deuterium neutron yield increases by more than an order of magnitude to 1.1×10^{13} (2 kJ deuterium-tritium equivalent) through a simultaneous increase in the applied magnetic field (from 10.4 to 15.9 T), laser preheat energy (from 0.46 to 1.2 kJ), and current coupling (from 16 to 20 MA). Individual parametric scans of the initial magnetic field and laser preheat energy show the expected trends, demonstrating the importance of magnetic insulation and the impact of the Nernst effect for this concept. A drive-current scan shows that present experiments operate close to the point where implosion stability is a limiting factor in performance, demonstrating the need to raise fuel pressure as drive current is increased. Simulations that capture these experimental trends indicate that another order of magnitude increase in yield on the Z facility is possible with additional increases of input parameters.

5.
Osteoarthritis Cartilage ; 24(6): 1029-35, 2016 06.
Article in English | MEDLINE | ID: mdl-26790721

ABSTRACT

OBJECTIVE: To determine if type III collagen is concentrated in the chymotrypsin-extractable collagen pool from osteoarthritic articular cartilage to assess its potential as a biomarker of Osteoarthritis (OA) pathogenic mechanisms. METHODS: Full thickness articular cartilage from grossly normal surfaces was analyzed from femoral heads, obtained at hip replacement surgery, from OA (n = 10) and fracture (n = 10) patients. Collagen, extracted by α-chymotrypsin, was characterized by SDS-PAGE/Western blot analysis, ELISA and immunohistochemistry using monoclonal antibodies specific to collagens types II and III. RESULTS: α-Chymotrypsin extracted more collagen from OA than control cartilage. The extractable pool included collagen types II and III from both OA and control hips. Importantly, OA cartilage contained 6-fold more collagen type III than control cartilage, based on ELISA. The estimated total tissue ratio of collagen III/II was in the 1-10% range for individual OA cartilage samples, based on pepsin-solubilized collagen using SDS-PAGE densitometry. Collagen type III N-propeptide trimers were the main molecular fragments seen on Western blot analysis of OA and control extracts. The chymotrypsin-extracted type II collagen gave primarily full-length α1(II) chains and chain fragments of α1(II) on Western blot analysis from both OA and control tissues. Immunohistochemistry showed that type III collagen was more concentrated in the upper half of OA cartilage and in the territorial matrix around individual chondrocytes and chondrocyte clusters. CONCLUSIONS: The findings confirm that collagen type III deposition occurs in adult articular cartilage but significantly more pronounced in osteoarthritic joints, presenting a potential marker of matrix repair or pathobiology.


Subject(s)
Cartilage, Articular , Chondrocytes , Chymotrypsin , Collagen Type II , Collagen Type III , Humans , Osteoarthritis
6.
Eur Radiol ; 26(12): 4231-4238, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27048538

ABSTRACT

OBJECTIVE: With a region of interest (ROI)-based approach 2-year-old children after congenital diaphragmatic hernia (CDH) show reduced MR lung perfusion values on the ipsilateral side compared to the contralateral. This study evaluates whether results can be reproduced by segmentation of whole-lung and whether there are differences between the ROI-based and whole-lung measurements. METHODS: Using dynamic contrast-enhanced (DCE) MRI, pulmonary blood flow (PBF), pulmonary blood volume (PBV) and mean transit time (MTT) were quantified in 30 children after CDH repair. Quantification results of an ROI-based (six cylindrical ROIs generated of five adjacent slices per lung-side) and a whole-lung segmentation approach were compared. RESULTS: In both approaches PBF and PBV were significantly reduced on the ipsilateral side (p always <0.0001). In ipsilateral lungs, PBF of the ROI-based and the whole-lung segmentation-based approach was equal (p=0.50). In contralateral lungs, the ROI-based approach significantly overestimated PBF in comparison to the whole-lung segmentation approach by approximately 9.5 % (p=0.0013). CONCLUSIONS: MR lung perfusion in 2-year-old children after CDH is significantly reduced ipsilaterally. In the contralateral lung, the ROI-based approach significantly overestimates perfusion, which can be explained by exclusion of the most ventral parts of the lung. Therefore whole-lung segmentation should be preferred. KEY POINTS: • Ipsilaterally, absolute lung perfusion after CDH is reduced in whole-lung analysis. • Ipsilaterally, the ROI- and whole-lung-based approaches generate identical results. • Contralaterally, the ROI-based approach significantly overestimates perfusion results. • Whole lung should be analysed in MR lung perfusion imaging. • MR lung perfusion measurement is a radiation-free parameter of lung function.


Subject(s)
Hernias, Diaphragmatic, Congenital/surgery , Lung/blood supply , Lung/diagnostic imaging , Magnetic Resonance Imaging/methods , Postoperative Care/methods , Regional Blood Flow/physiology , Blood Volume , Child, Preschool , Contrast Media , Female , Humans , Image Enhancement , Male , Reproducibility of Results
7.
Radiologe ; 56(2): 113-23, 2016 Feb.
Article in German | MEDLINE | ID: mdl-26796337

ABSTRACT

CLINICAL/METHODICAL ISSUE: Magnetic resonance imaging (MRI) is recognized for its superior tissue contrast while being non-invasive and free of ionizing radiation. Due to the development of new scanner hardware and fast imaging techniques during the last decades, access to tissue and organ functions became possible. One of these functional imaging techniques is perfusion imaging with which tissue perfusion and capillary permeability can be determined from dynamic imaging data. STANDARD RADIOLOGICAL METHODS: Perfusion imaging by MRI can be performed by two approaches, arterial spin labeling (ASL) and dynamic contrast-enhanced (DCE) MRI. While the first method uses magnetically labelled water protons in arterial blood as an endogenous tracer, the latter involves the injection of a contrast agent, usually gadolinium (Gd), as a tracer for calculating hemodynamic parameters. PERFORMANCE: Studies have demonstrated the potential of perfusion MRI for diagnostics and also for therapy monitoring. ACHIEVEMENTS: The utilization and application of perfusion MRI are still restricted to specialized centers, such as university hospitals. A broad application of the technique has not yet been implemented. PRACTICAL RECOMMENDATIONS: The MRI perfusion technique is a valuable tool that might come broadly available after implementation of standards on European and international levels. Such efforts are being promoted by the respective professional bodies.


Subject(s)
Blood Flow Velocity/physiology , Blood Vessels/physiology , Blood Volume Determination/methods , Blood Volume/physiology , Gadolinium/pharmacokinetics , Magnetic Resonance Angiography/methods , Animals , Computer Simulation , Contrast Media/pharmacokinetics , Humans , Image Interpretation, Computer-Assisted/methods , Models, Cardiovascular
8.
Proc Natl Acad Sci U S A ; 108(31): 12811-4, 2011 Aug 02.
Article in English | MEDLINE | ID: mdl-21768363

ABSTRACT

Active cigarette smoking increases oxidative damage, DNA adducts, DNA strand breaks, chromosomal aberrations, and heritable mutations in sperm. However, little is known regarding the effects of second-hand smoke on the male germ line. We show here that short-term exposure to mainstream tobacco smoke or sidestream tobacco smoke (STS), the main component of second-hand smoke, induces mutations at an expanded simple tandem repeat locus (Ms6-hm) in mouse sperm. We further show that the response to STS is not linear and that, for both mainstream tobacco smoke and STS, doses that induced significant increases in expanded simple tandem repeat mutations in sperm did not increase the frequencies of micronucleated reticulocytes and erythrocytes in the bone marrow and blood of exposed mice. These data show that passive exposure to cigarette smoke can cause tandem repeat mutations in sperm under conditions that may not induce genetic damage in somatic cells. Although the relationship between noncoding tandem repeat instability and mutations in functional regions of the genome is unclear, our data suggest that paternal exposure to second-hand smoke may have reproductive consequences that go beyond the passive smoker.


Subject(s)
Mutagens/toxicity , Nicotiana/chemistry , Smoke/adverse effects , Spermatozoa/drug effects , Animals , Dose-Response Relationship, Drug , Erythrocytes/drug effects , Erythrocytes/metabolism , Male , Mice , Micronuclei, Chromosome-Defective/chemically induced , Micronucleus, Germline/drug effects , Minisatellite Repeats/genetics , Mutation/drug effects , Reticulocytes/drug effects , Reticulocytes/metabolism , Spermatozoa/metabolism , Tandem Repeat Sequences/genetics , Time Factors
9.
Radiologie (Heidelb) ; 64(5): 366-372, 2024 May.
Article in German | MEDLINE | ID: mdl-38587632

ABSTRACT

STANDARD RADIOLOGICAL METHODS: Fetal: Ultrasound and magnetic resonance imaging (MRI); postnatal: conventional X­ray diagnostics, computed tomography (CT) and MRI. METHODICAL INNOVATIONS: MRI-based lung ventilation and perfusion measurement. PRACTICAL RECOMMENDATIONS: Lifelong follow-up care should be provided, in which radiology is part of the treatment team.


Subject(s)
Hernias, Diaphragmatic, Congenital , Female , Humans , Infant, Newborn , Male , Pregnancy , Aftercare , Hernias, Diaphragmatic, Congenital/diagnostic imaging , Hernias, Diaphragmatic, Congenital/surgery , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Ultrasonography, Prenatal/methods
10.
Nat Genet ; 11(1): 87-9, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7550321

ABSTRACT

The chondrodysplasias are a heterogeneous group of disorders characterized by abnormal growth or development of cartilage. Current classification is based on mode of inheritance as well as clinical, histologic, and/or radiographic features. A clinical spectrum of chondrodysplasia phenotypes, ranging from mild to perinatal lethal, is due to defects in the gene for type II collagen, COL2A1. This spectrum includes Stickler syndrome, Kniest dysplasia, spondyloepiphyseal dysplasia congenita (SEDC), achondrogenesis type II, and hypochondrogenesis. Individuals affected with these disorders exhibit abnormalities of the growth plate, nucleus pulposus, and vitreous humor, which are tissues that contain type II collagen. The Strudwick type of spondyloepimetaphyseal dysplasia (SEMD) is characterized by disproportionate short stature, pectus carinatum, and scoliosis, as well as dappled metaphyses (which are not seen in SEDC). The phenotype was first described by Murdoch and Walker in 1969, and a series of 14 patients was later reported by Anderson et al. The observation of two affected sibs born to unaffected parents led to the classification of SEMD Strudwick as an autosomal recessive disorder. We now describe the biochemical characterization of defects in alpha 1(II) collagen in three unrelated individuals with SEMD Strudwick, each of which is due to heterozygosity for a unique mutation in COL2A1. Our data support the hypothesis that some cases, if not all cases, of this distinctive chondrodysplasia result from dominant mutations in COL2A1, thus expanding the clinical spectrum of phenotypes associated with this gene.


Subject(s)
Collagen/genetics , Genes, Dominant , Osteochondrodysplasias/genetics , Adult , Base Sequence , Child , Collagen/classification , Cysteine , DNA Mutational Analysis , DNA, Complementary/genetics , Female , Glycine , Humans , Infant, Newborn , Male , Molecular Sequence Data , Osteochondrodysplasias/classification , Pedigree , Phenotype , Point Mutation
11.
Radiologie (Heidelb) ; 63(10): 729-735, 2023 Oct.
Article in German | MEDLINE | ID: mdl-37407747

ABSTRACT

CLINICAL/METHODICAL ISSUE: Differentiating between septic arthritis and transient synovitis can be challenging but is very important as a late diagnosis of septic arthritis can lead to sepsis and joint damage. For correct diagnosis and prediction of complications, the right combination of physical examination, laboratory and radiological studies is needed. STANDARD RADIOLOGICAL METHODS: Hip ultrasound is easy to learn and has a high sensitivity for joint effusion. Faster diagnosis and therapy are possible due to increasing use of ultrasound. Magnetic resonance imaging (MRI) is primarily used to rule out co-infections (osteomyelitis, pyomyositis) and differential diagnoses. X­ray is typically nonremarkable in septic arthritis. PRACTICAL RECOMMENDATIONS: Routine use of ultrasound in nontraumatic pediatric hip pain. Generous use of MRI in case of elevated inflammatory markers or inconclusive clinical findings. Using only few sequences may be appropriate to avoid sedation, primarily fluid sensitive sequences (fat-saturated T2, TIRM, STIR), in case of positive findings, accompanied by T1-weighted images.


Subject(s)
Arthritis, Infectious , Synovitis , Child , Humans , Hip Joint/diagnostic imaging , Hip Joint/pathology , Synovitis/diagnostic imaging , Synovitis/pathology , Arthritis, Infectious/diagnostic imaging , Arthritis, Infectious/pathology , Hip/pathology , Radiography
12.
Radiologie (Heidelb) ; 63(4): 275-283, 2023 Apr.
Article in German | MEDLINE | ID: mdl-36811691

ABSTRACT

CLINICAL/METHODOLOGICAL ISSUE: Due to active participation of children and adolescents in school sports as well as in club sports, sporting injuries in childhood are common. Because skeletal maturity is not yet complete, injury patterns in children differ from sporting injuries in adults. Knowledge of the pathophysiologic characteristics, as well as knowledge of typical injury sequelae, is of great relevance to radiologists. This review article therefore deals with common acute and chronic sporting injuries in children. STANDARD RADIOLOGICAL METHODS: Basic diagnostic imaging comprises conventional X­ray imaging in two planes. In addition, sonography, magnetic resonance imaging (MRI) and computed tomography (CT) are used. PRACTICAL RECOMMENDATIONS: Close consultation with clinical colleagues and knowledge of childhood-specific injuries help identify sports-associated trauma sequelae.


Subject(s)
Athletic Injuries , Sports , Adult , Humans , Child , Adolescent , Athletic Injuries/diagnostic imaging , Athletic Injuries/etiology , Magnetic Resonance Imaging
13.
Rev Sci Instrum ; 94(5)2023 May 01.
Article in English | MEDLINE | ID: mdl-37184347

ABSTRACT

We report on progress implementing and testing cryogenically cooled platforms for Magnetized Liner Inertial Fusion (MagLIF) experiments. Two cryogenically cooled experimental platforms were developed: an integrated platform fielded on the Z pulsed power generator that combines magnetization, laser preheat, and pulsed-power-driven fuel compression and a laser-only platform in a separate chamber that enables measurements of the laser preheat energy using shadowgraphy measurements. The laser-only experiments suggest that ∼89% ± 10% of the incident energy is coupled to the fuel in cooled targets across the energy range tested, significantly higher than previous warm experiments that achieved at most 67% coupling and in line with simulation predictions. The laser preheat configuration was applied to a cryogenically cooled integrated experiment that used a novel cryostat configuration that cooled the MagLIF liner from both ends. The integrated experiment, z3576, coupled 2.32 ± 0.25 kJ preheat energy to the fuel, the highest to-date, demonstrated excellent temperature control and nominal current delivery, and produced one of the highest pressure stagnations as determined by a Bayesian analysis of the data.

14.
Clin Genet ; 82(5): 453-9, 2012 Nov.
Article in English | MEDLINE | ID: mdl-21955071

ABSTRACT

Deficiency of any component of the ER-resident collagen prolyl 3-hydroxylation complex causes recessive osteogenesis imperfecta (OI). The complex modifies the α1(I)Pro986 residue and contains cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1) and cyclophilin B (CyPB). Fibroblasts normally secrete about 10% of CRTAP. Most CRTAP mutations cause a null allele and lethal type VII OI. We identified a 7-year-old Egyptian boy with non-lethal type VII OI and investigated the effects of his null CRTAP mutation on collagen biochemistry, the prolyl 3-hydroxylation complex, and collagen in extracellular matrix. The proband is homozygous for an insertion/deletion in CRTAP (c.118_133del16insTACCC). His dermal fibroblasts synthesize fully overmodified type I collagen, and 3-hydroxylate only 5% of α1(I)Pro986. CRTAP transcripts are 10% of control. CRTAP protein is absent from proband cells, with residual P3H1 and normal CyPB levels. Dermal collagen fibril diameters are significantly increased. By immunofluorescence of long-term cultures, we identified a severe deficiency (10-15% of control) of collagen deposited in extracellular matrix, with disorganization of the minimal fibrillar network. Quantitative pulse-chase experiments corroborate deficiency of matrix deposition, rather than increased matrix turnover. We conclude that defects of extracellular matrix, as well as intracellular defects in collagen modification, contribute to the pathology of type VII OI.


Subject(s)
Collagen Type I/metabolism , Extracellular Matrix Proteins/genetics , Genes, Recessive , Osteogenesis Imperfecta/genetics , Alleles , Child , Collagen Type I, alpha 1 Chain , Cyclophilins/genetics , Cyclophilins/metabolism , Egypt , Extracellular Matrix Proteins/metabolism , Fibroblasts/metabolism , Gene Deletion , Homozygote , Humans , Male , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Molecular Chaperones , Mutation , Osteogenesis Imperfecta/metabolism , Osteogenesis Imperfecta/pathology , Prolyl Hydroxylases , Protein Processing, Post-Translational , Proteoglycans/genetics , Proteoglycans/metabolism
15.
Langmuir ; 28(25): 9395-404, 2012 Jun 26.
Article in English | MEDLINE | ID: mdl-22662960

ABSTRACT

An original diffraction model for the analysis of grazing-incidence small-angle X-ray scattering (GISAXS) from the nanoparticle Langmuir films was developed. This model relies on the concept of the 2D hexagonal paracrystal and employs the distorted-wave Born approximation that is relevant for GISAXS measurements at the air/water interface when the angle of incidence is close to the critical value. The model comprises the cases of the close-packed nanoparticle monolayer and bilayer with the AB-type layer stacking. In this way, both the lateral (along the interface) and vertical (normal to the interface) correlations of the nanoparticle positions can be analyzed. The model was applied to an in situ GISAXS study of the formation of a silver nanoparticle Langmuir film during compression at the air/water interface in the Langmuir-Blodgett trough. Spherical nanoparticles of 5.8 ± 0.6 nm diameter were employed. Different compression stages starting from the submonolayer up to the monolayer collapse via bilayer formation were analyzed in terms of the mean lateral interparticle distance, degree of paracrystal disorder, interlayer distance, vertical disorder, and layer-stacking type in the bilayer as well as the ratio between the monolayer and bilayer coverage in the final film. The model developed is applicable to any nanoparticle Langmuir film formed at the air/liquid interface to extract structural parameters on the nanoscale. The particular results obtained have direct implications on the preparation of silver plasmonic templates with "hot spots" for surface-enhanced Raman scattering.

16.
Eur J Appl Physiol ; 112(5): 1699-708, 2012 May.
Article in English | MEDLINE | ID: mdl-21881949

ABSTRACT

The focus of this study was to assess exercise-induced alterations of circulating dendritic cell (DC) subpopulations and toll-like receptor (TLR) expression after marathon running. Blood sampling was performed in 15 obese non-elite (ONE), 16 lean non-elite (LNE) and 16 lean elite (LE) marathon runners pre- and post-marathon as well as 24 h after the race. Circulating DC-fractions were measured by flow-cytometry analyzing myeloid DCs (BDCA-1+) and plasmacytoid DCs (BDCA-2+). We further analyzed the (TLR) -2/-4/-7 in peripheral blood mononuclear cells (rt-PCR/Western Blot) and the cytokines CRP, IL-6, IL-10, TNF-α and oxLDL by ELISA. After the marathon, BDCA-1 increased significantly in all groups [LE (pre/post): 0.35/0.47%; LNE: 0.26/0.50% and ONE: 0.30/0.49%; all p < 0.05]. In contrast, we found a significant decrease for BDCA-2 directly after the marathon (LE: 0.09/0.01%; LNE: 0.12/0.03% and ONE: 0.10/0.02%; all p < 0.05). Levels of TLR-7 mRNA decreased in all groups post-marathon (LE 44%, LNE 67% and ONE 52%; all p < 0.01), with a consecutive protein reduction (LE 31%, LNE 52%, ONE 42%; all p < 0.05) 24 h later. IL-6 and IL-10 levels increased immediately after the run, whereas increases of TNF-α and CRP-levels were seen after 24 h. oxLDL levels remained unchanged post-marathon. In our study population, we did not find any relevant differences regarding training level or body weight. Prolonged endurance exercise induces both pro- and anti-inflammatory cytokines. Anti-inflammatory cytokines, such as IL-10, may help to prevent excessive oxidative stress. Marathon running is associated with alterations of DC subsets and TLR-expression independent of training level or body weight. Myeloid and plasmacytoid DCs are differently affected by the excessive physical stress. Immunomodulatory mechanisms seem to play a key role in the response and adaptation to acute excessive exercise.


Subject(s)
Cytokines/metabolism , Dendritic Cells/cytology , Leukocytes, Mononuclear/metabolism , Running/physiology , Toll-Like Receptors/metabolism , Adult , Blotting, Western , C-Reactive Protein/analysis , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Immunomodulation , Leukocytes, Mononuclear/cytology , Lipoproteins, LDL/blood , Male , Middle Aged , Real-Time Polymerase Chain Reaction
17.
Am J Med Genet A ; 155A(11): 2865-70, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21964860

ABSTRACT

Mutations of proteins involved in posttranslational modification of collagen type I can cause osteogenesis imperfecta (OI) inherited in a recessive pattern. The cartilage-associated protein (CRTAP) is part of a heterotrimeric complex (together with prolyl-3-hydroxylase-1 [P3H1] and cyclophilin B) that 3-hydroxylates the alpha 1 chain of collagen type I at proline residue 986 and plays a collagen chaperon role. CRTAP mutations usually cause severe OI. We report on a patient with OI and a homozygous in-frame deletion in CRTAP and a severe form of OI. The girl was born with markedly deformed long bones. Despite intravenous bisphosphonate treatment, she developed multiple vertebral compression fractures and severe scoliosis and at 4 years of age was able to sit only with support. Although CRTAP transcript levels were normal in the patient's fibroblasts, protein levels of both CRTAP and P3H1 were severely reduced. The degree of 3-hydroxylation at proline residue 986 was also decreased. This report characterizes a patient with a CRTAP small in-frame deletion. We are unaware of prior reports of this finding. We suggest that this deletion affects crucial amino acids that are important for the interaction and/or stabilization of CRTAP and P3H1.


Subject(s)
Extracellular Matrix Proteins/genetics , Osteogenesis Imperfecta/genetics , Blotting, Western , Child, Preschool , Cyclophilins/metabolism , Exons , Extracellular Matrix Proteins/metabolism , Female , Fetus/abnormalities , Fluorescent Antibody Technique , Fractures, Bone/diagnosis , Fractures, Bone/genetics , Fractures, Bone/pathology , Homozygote , Humans , Hydroxylation , Infant , Infant, Newborn , Membrane Glycoproteins/metabolism , Molecular Chaperones , Osteogenesis Imperfecta/diagnosis , Osteogenesis Imperfecta/metabolism , Osteogenesis Imperfecta/pathology , Pedigree , Pregnancy , Pregnancy Trimester, Third , Primary Cell Culture , Proline/metabolism , Prolyl Hydroxylases , Proteoglycans/metabolism , Scoliosis/congenital , Scoliosis/diagnosis , Scoliosis/genetics , Scoliosis/pathology , Sequence Deletion
18.
Nat Med ; 7(7): 833-9, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11433349

ABSTRACT

We provide anatomic and functional evidence that nicotine induces angiogenesis. We also show that nicotine accelerates the growth of tumor and atheroma in association with increased neovascularization. Nicotine increased endothelial-cell growth and tube formation in vitro, and accelerated fibrovascular growth in vivo. In a mouse model of hind-limb ischemia, nicotine increased capillary and collateral growth, and enhanced tissue perfusion. In mouse models of lung cancer and atherosclerosis, we found that nicotine enhanced lesion growth in association with an increase in lesion vascularity. These effects of nicotine were mediated through nicotinic acetylcholine receptors at nicotine concentrations that are pathophysiologically relevant. The endothelial production of nitric oxide, prostacyclin and vascular endothelial growth factor might have a role in these effects.


Subject(s)
Arteriosclerosis/complications , Carcinoma, Lewis Lung/blood supply , Carcinoma, Lewis Lung/pathology , Lung Neoplasms/blood supply , Lung Neoplasms/pathology , Neovascularization, Pathologic/etiology , Nicotine/pharmacology , Animals , Arteriosclerosis/pathology , Mice , Mice, Inbred C57BL
19.
J Wound Care ; 20(12): 592-8, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22240886

ABSTRACT

OBJECTIVE: To test the hypothesis that topically applied calcium glycerophosphate (CGP) would improve the appearance of the wound following bilateral knee replacement. METHOD: Healthy patients, aged 45-75 years, scheduled for bilateral total-knee replacement surgery were recruited into the study. One knee was randomly assigned to the treatment group, while the contralateral knee was designated the control (standard care). Subjects were instructed to apply a preparation of 10% CGP in an aqueous lotion to the treated knee once daily for 42 days, starting at the third postoperative day. Functional sealing and cosmetic appearance of the incision were evaluated by two surgeons by direct examination of the patient and then by two experienced assessors from photographs. The investigators qualitatively scored the intensity and extent of erythema along the incision and over the entire knee, the appearance of visible oedema along the incision and over the knee, and the overall clinical impression of wound healing. All four assessors were blinded to the subjects' allocation and the latter two assessors to the initial investigators' assessments. Subjects were also followed up for an additional 46 weeks, giving a total study duration of 12 months. RESULTS: Twenty patients completed the study. Statistical analysis showed that both the area and intensity of erythema along the incision were significantly reduced in the treated vs untreated knee over the entire study period. The analysis further showed that treatment significantly reduced oedema, both along the incision and across the entire knee. The differences were most marked at the seventh postoperative day and diminished with time. No adverse effects were observed for any patient, in either treated or untreated knees. CONCLUSION: These data demonstrate that postoperative application of 10% CGP could improve the appearance of the wound following total knee arthroplasty.


Subject(s)
Arthroplasty, Replacement, Knee , Glycerophosphates/administration & dosage , Wound Healing/drug effects , Administration, Topical , Aged , Cicatrix/prevention & control , Erythema/prevention & control , Female , Humans , Knee Joint/physiopathology , Male , Middle Aged , Pain Measurement , Range of Motion, Articular , Wound Healing/physiology
20.
Nanotechnology ; 21(38): 385702, 2010 Sep 24.
Article in English | MEDLINE | ID: mdl-20739738

ABSTRACT

An in situ small-angle x-ray scattering study of the nanoparticle displacement in a self-assembled monolayer as a function of a supporting membrane strain is presented. The average nanoparticle spacing is 6.7 nm in the unstrained state and increases in the applied force direction, following linearly the membrane strain which reaches the maximum value of 11%. The experimental results suggest a continuous mutual shift of the nanoparticles and their gradual separation with the growing stress rather than nanoparticle islands formation. No measurable shift of the nanoparticles was observed in the direction perpendicular to the applied stress.

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