[Con: patient-controlled analgesia (PCA)].
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Biomedical subjects
Publications and source records attributed to M Fritz.
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Hypersensitivity to nickel (Ni) represents the most common manifestation of contact allergy in humans. The role of metal-specific T cells in this disease is well established, but the molecular interactions involved in their activation are poorly understood. We examined the T cell receptor (TCR) repertoire in T cells activated with either NiSO4 or NiSO4-treated human serum albumin from six allergic patients. For the three most hyperreactive donors, we found a strong over-representation of the TCR BV17 element. TCR sequencing for one of these donors revealed an additional skewing for AV1 as well as a selection for an N region encoded argine at position 95 of the BV17 complementarity determining region (CDR)3. Since Arg is not known to participate in Ni complexing, we suppose that this selection is driven by contacts with peptide rather than nickel. However, the CDR1 of BV17 contains a unique combination of amino acids (HDA) that bears similarities to known motifs in Ni-binding proteins or peptides. We therefore propose that the severe hypersensitivity reactions found in BV17 over-expressors may be the result of Ni2+ ions bridging the germ-line-encoded BV17 CDR1 loop to corresponding sites in the major histocompatibility complex/peptide complex and thereby creating a superantigen-like enhancement of weak TCR-peptide contacts.
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BACKGROUND: Several investigations reveal that long-term exposure to whole-body vibrations can induce degenerative changes in the lumbar spine. In analogy to the activities of lifting or carrying loads, an assessment of the health risk should be possible if the forces transmitted in the spine during vibration stress are known. METHODS: To estimate the spine forces a biomechanical model was developed. In the model the human trunk, neck, and head were represented by 10 rigid bodies connected by visco-elastic elements. Some 56 force elements imitated the muscles of the body. The motion equations of the model were derived by means of the dynamics of systems of rigid bodies. RESULTS: The transfer functions of the model accelerations in x- and z-direction satisfactorily corresponded to data reported in the literature. Transfer functions were computed between the forces transmitted from the seat to the pelvis and in the lumbar spine, respectively. CONCLUSION: The forces between seat and pelvis were measured, then the spine forces were computed by means of the transfer functions. To assess the health risk the computed forces must be compared with the strength of the spine because the strength is dependent on the age and gender of the worker and decreases with the number of load cycles.
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We have measured force curves as a function of the lateral position on top of human platelets with the atomic force microscope. These force curves show the indentation of the cell as the tip loads the sample. By analyzing these force curves we were able to determine the elastic modulus of the platelet with a lateral resolution of approximately 100 nm. The elastic moduli were in a range of 1-50 kPa measured in the frequency range of 1-50 Hz. Loading forces could be controlled with a resolution of 80 pN and indentations of the platelet could be determined with a resolution of 20 nm.
Height fluctuations over three different proteins, immunoglobulin G, urease, and microtubules, have been measured using an atomic force microscope (AFM) operating in fluid tapping mode. This was achieved by using a protein-tracking system, where the AFM tip was periodically repositioned above a single protein molecule (or structure) as thermal drifting occurred. Height (z-piezo signal) data were taken in 1 - or 2-s time slices with the tip over the molecule and compared to data taken on the support. The measured fluctuations were consistently higher when the tip was positioned over the protein, as opposed to the support the protein was adsorbed on. Similar measurements over patches of an amphiphile, where the noise was identical to that on the support, suggest that the noise increase is due to some intrinsic property of proteins and is not a result of different tip-sample interactions over soft samples. The orientation of the adsorbed proteins in these preliminary studies was not known; thus it was not possible to make correlations between the observed motion and specific protein structure or protein function beyond noting that the observed height fluctuations were greater for an antibody (anti-bovine IgG) and an enzyme (urease) than for microtubules.
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We have imaged mica coated with thin gelatin films in water, propanol, and mixtures of these two liquids by atomic force microscopy (AFM). The elastic modulus (Young's modulus) can be tuned from 20 kPa to more than 0.1 GPa depending on the ratio of propanol to water. The resolution is best in pure propanol, on the order of 20 nm, and becomes worse for the softer samples. The degradation in resolution can be understood by considering the elastic indentation of the gelatin caused by the AFM tip. This indentation becomes larger and thus the contact area becomes larger the softer the sample is. Therefore this study may be used to estimate the resolution to be expected with an AFM on other soft samples, such as cells. Nondestructive imaging was possible only by imaging at forces < 1 nN. This was difficult to achieve in contact mode because of drift in the zero load deflection of the cantilever, supposedly caused by temperature drift, but straightforward in tapping mode.
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This report describes the succession of putative peri-implant pathogens in partially dentate monkeys after dental implantation and prosthetic reconstruction. Tooth and implant (6 root-end form, 4 blade-vent implants) sites in eight monkeys were monitored microbiologically and clinically during the pre-implant stage, abutment connection stage, bridge placement stage, and three and six months after the bridge placement stage. Tooth and implant sites were cleaned monthly post-extraction. Microbiological studies included dark field microscopy, selective and non-selective culture, and primary phenotypic characterization of culture isolates. After implant surgery, the median proportion of several putative peri-implant pathogens studied were significantly elevated. Following fixture placement, P. intermedia replaced P. melaninogenica as the predominant Black Pigmented Anaerobic Bacilli (BPAB) in the mouth. After abutment connection stage, levels of P. intermedia, A. actinomycetemcomitans, F. nucleatun, Haemophilus sp. and spirochetes were significantly elevated at implant and tooth sites. Three months after bridge installations, P. intermedia and A. actinomycetemcomitans remained significantly elevated at implant sites. At six months after bridge installation, levels of P. intermedia, F. nucleatum and A. actinomycetemcomitans declined significantly relative to levels at three months. Porphyromonas sp. and spirochetes were not significantly elevated although their levels correlated with gingival redness. P. intermedia, Porphyromonas sp. and spirochetes levels correlated significantly with probing depth. Correlation was detected between P. gingivalis and spirochetes; and between A. actinomycetemcomitans and F. nucleatum. Our studies show a transitional increase in levels of several organisms resembling putative pathogens of human peri-implant infection, associated with implant placements in partially edentulous mouths and supports early prophylactic interventions to control their levels.
A depot preparation of Estriol (Ortho Gynest D; 3.5 mg Estriol, intravaginal) was applied for 3 months to 135 postmenopausal women with urinary incontinence. Before and after treatment the symptoms of incontinence were scaled by the Gaudenz questionnaire. 8 symptoms were tested for statistical significance. All of them had significantly improved after treatment. 63% of patients showed improvement of their incontinence, urinary stress incontinence improved in 50%. Dysuria was reported by 14 patients before treatment, by none after treatment. Daytime and nighttime micturition frequency both decreased significantly, also subjective impairment by incontinence. Thus the local application of Estriol ovula represents an effective mode of primary treatment (maintenance therapy, one dose per week) in postmenopausal patients with urinary incontinence.
Despite differences between pediatric and adult pacing have narrowed, implantation procedures in children require special considerations. Patients are physically smaller, they often suffer from complex cardiac defects necessitating further open heart surgery procedures. As there are no pacemakers and only some electrodes designed specially for pediatric pacing, selection of appropriate systems is important. At this time we care for 18 patients with a mean age of 11.5 +/- 6.5 years (= 138.6 +/- 78.4 months, range 10 to 280 months). 50% of them received a permanent pacemaker because of surgically induced heart block, 33.3% because of congenital complete heart block and 16.7% because of sick sinus syndrome. Mean age at first pacemaker implantation was 57 +/- 42 months (Range 0 to 120 months). 72.2% of these children had their first pacing system implanted in the abdominal wall with an epicardial electrode, 27.8% had endovenous endocardial electrodes with subpectoral generator placement. 72.2% of our patients had already revisions of their pacing systems, mean longevity time of pulse generators were 36.8 +/- 21.8 months. Upgrading from single chamber pacing to physiological AV-sequential dual chamber pacing was performed at a mean age of 9.0 +/- 2.8 years (= 108.3 +/- 33.9 months, range 66 to 154 months). By reviewing our patient data we want to discuss present standards and guidelines of surgical pacemaker therapy in children and how to prevent potential complications.
The height fluctuations on top of the protein lysozyme adsorbed on mica were measured locally with an atomic force microscope operated in tapping mode in liquid. Height fluctuations of an apparent size of 1 nanometer that lasted for about 50 milliseconds were observed over lysozyme molecules when a substrate (oligoglycoside) was present. In the presence of the inhibitor chitobiose, these height fluctuations decreased to the level without the oligoglycoside. The most straightforward interpretation of these results is that the height fluctuations correspond to the conformational changes of lysozyme during hydrolysis. It is also possible, however, that the height fluctuations are, at least in part, the result of a different height or elasticity of the transient complex of lysozyme plus the substrate.
The redistribution of platelet constituents during activation is essential for their physiological function of maintaining hemostasis. We report here about real time investigations of the activation of native human platelets under physiological conditions from the initial formation of filopodia to the fully spread form by atomic force microscopy. We followed the trafficking of granules and their interaction with the plasma membrane within single cells. Our results show movement of certain granula towards the lamellipodia. Analysis of this rearrangement and the subsequent enlargement of the platelet surface reveals details of the membrane spreading process. Images of living cells are presented that show the distribution of cytoskeletal components and membrane-bound filaments at a resolution of better than 50 nm. The local minimum forces between the tip and the platelets were estimated to be smaller than 60 pN. A model for the elastic contributions of the glycocalix to the tip/membrane interaction was developed using the theory of grafted polymers.
Force curves were recorded as the sample was raster-scanned under the tip. This opens new opportunities for imaging with the atomic force microscope: several characteristics of the samples can be measured simultaneously, for example, topography, adhesion forces, elasticity, van der Waals, and electrostatic interactions. The new opportunities are illustrated by images of several characteristics of thin metal films, aggregates of lysozyme, and single molecules of DNA.
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