Biomedical subjects
Publications and source records attributed to M Mueller.
We describe a case of delayed resurfacing of the right breast using the abdominal skin as a full-thickness graft in a 38-year-old woman who sustained a scald injury in childhood. The postoperative results are shown.
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We present a new MALD1 sample preparation technique for peptide analysis using the matrix alpha-cyano-4-hydroxy-cinnamic acid (CHCA) and prestructured sample supports. The preparation integrates sample purification, based on the affinity of microcrystalline CHCA for peptides, thereby simplifying the analysis of crude peptide mixtures. Enzymatic digests can thus be prepared directly, without preceding purification. Prepared samples are homogeneous, facilitating automatic spectra acquisition. This method allows preparation of large numbers of samples with little effort and without the need for automation. These features make the described preparation suitable for cost-efficient high-throughput protein identification. Performance of the sample preparation is demonstrated with in situ proteolytic digests of human brain proteins separated by two-dimensional gel electrophoresis.
The platelet function dose-response to incremental abciximab (Reopro, Eli Lilly/Centocor, Indianapolis, IN) bolus dosing during percutaneous coronary intervention (PCI) was evaluated in 85 patients using a point-of-service platelet function assay. Patients received incremental bolus doses of abciximab at 10- to 20-min intervals; platelet function was measured at 10-min intervals during dosing. The percentage of patients achieving > or = 80% inhibition of platelet function after 50%, 75%, and 100% of a standard abciximab bolus was 40%, 87%, and 95%, respectively. There were no significant associations between the platelet function dose-response to abciximab and age, weight, platelet count, hematocrit, heparin dose, peak activated clotting time, thienopyridine use prior to PCI, gender, cigarette smoking, diabetes mellitus, or clinical syndrome. This study demonstrated significant interpatient variability in platelet function dose-response to abciximab with a substantial proportion (87%) of patients achieving high-level platelet function inhibition with less than the standard abciximab bolus dose.
The efficiency of nuclear transfer (NT) using two primary cultures of fetal fibroblasts (FF1 and FF2) was compared vs. the same cultures transfected with an expression vector in which the bovine prochymosin coding sequence is placed under the control of the bovine alpha(S1)-casein promoter (TFF1 and TFF2). In addition, fibroblasts of a cloned transgenic fetus (TRFF1) derived from TFF1 and ear skin fibroblasts of a 1-month-old cloned transgenic calf (TRCF1) derived from TRFF1 were used as nuclear donors. Embryos reconstructed from FF1 (44%) and FF2 (52%) developed to the blastocyst stage at a significantly (P < 0.05) higher rate than those derived from TFF1 (24%) and TFF2 (27%). The proportions of cleaved embryos and blastocysts were significantly (P < 0.05) higher with TRFF1 than with TRCF1 used as nuclear donors (75 vs. 66% and 33 vs. 16%, respectively). Transfer of NT embryos derived from FF2 and TFF2 to recipients resulted in similar pregnancy rates on day 30 (52 and 48%, respectively). However, with TFF2 embryos, the majority of pregnancies (8/11; 73%) was lost in the first and second trimesters of gestation, whereas 4/11 (36%) pregnancies with FF2 embryos were lost during the full period of in vivo development. Of 11 FF2 and 6 TFF2 born calves (25 and 13% of transferred embryos, respectively), 6 and 3 survived including one oversized FF2 calf. After transfer of TRFF1 and TRCF1 NT embryos to recipients, initial pregnancy rate was as a tendency higher in the TRFF1 (49%) than in the TRCF1 group (30%). The majority (14/17) of TRFF1 pregnancies and all TRCF1 pregnancies were lost in the first and second trimester. A high proportion of TRFF1 calves (5/8) showed increased body weights, and only two calves which were also large survived. These findings demonstrate that (i) extended culture associated with transfection and selection procedures may induce changes of donor cells which markedly decrease the efficiency of nuclear transfer and (ii) these changes are not reversed by recloning.
This pilot study evaluated hydroxyapatite (HA) implants (Endobon) into bone with magnetic resonance imaging (MRI). Nineteen patients (median age 57 years; range 18-67 years) have been evaluated. Eight received granulated HA into vertebral bodies after trauma, while 11 received HA blocks into extremity bones after trauma (n = 8) or fibrous dysplasia (n = 2). In a 1.5-T MR scanner, transversal T1-weighted, flash, 2-dimensional images were obtained. Signal intensities were measured in regions of interest (ROI) from the centre and periphery of HA, trabecular bone, fat and air before and after gadolinium (Gd) contrast enhancement, and the signal-to-noise ratio (SNR) was calculated. After Gd application the SNR in HA increased significantly, peripherally (11.7 without vs 18.2 with Gd, P = 0.003) more than in the centre (7.9 without vs 11.9 with Gd, P = 0.007). The SNR of the HA was higher in patients with block implants compared with granulated HA (P > 0.008). After Gd application, granulated HA enhances significantly less than HA blocks. During insertion of HA, the granulated form is compressed more and is therefore more compact than the HA block. This might hinder integration into the bone structure and the blood supply. SNR of the HA margin was higher than centrally, which might be due to granulomatous tissue after trauma and/or operation or beginning marginal integration.
Macrophages play a central role in the pathogenesis of peripheral neuropathy but the role of resident endoneurial macrophages is undefined because no discriminating markers exist to distinguish them from infiltrating hematogenous macrophages. We identified and characterized resident endoneurial macrophages during Wallerian degeneration in radiation bone marrow chimeric rats created by transplanting wild-type Lewis rat bone marrow into irradiated TK-tsa transgenic Lewis rats. In such animals, resident cells carry the transgene, whereas hematogenous cells do not. As early as 2 days after sciatic nerve crush and before the influx of hematogenous macrophages, resident transgene-positive endoneurial macrophages underwent morphological and immunophenotypic signs of activation. At the same time, resident macrophages phagocytosing myelin were found, and proliferation was detected by bromodeoxyuridine incorporation. Continuous bromodeoxyuridine feeding revealed that resident endoneurial macrophages sequentially retracted their processes, proliferated, and expressed the ED1 antigen, rendering them morphologically indistinguishable from hematogenous macrophages. Resident endoneurial macrophages thus play an early and active role in the cellular events after nerve lesion before hematogenous macrophages enter the nerve. They may thus be critically involved in the pathogenesis of peripheral neuropathy particularly at early stages of the disease and may act as sensors of pathology much like their central nervous system counterparts, the microglial cells.
OBJECTIVES: Patients undergoing cardiopulmonary bypass frequently manifest generalized systemic inflammation and occasionally manifest serious multiorgan failure. Inflammatory responses of bypass are triggered by contact of blood with artificial surfaces of the bypass circuits, surgical trauma, and ischemia-reperfusion injury. We studied the effects of specific inhibition of the alternative complement cascade by using an anti-factor D monoclonal antibody (166-32) in extracorporeal circulation of human whole blood used as a simulated model of cardiopulmonary bypass. METHODS: Five healthy blood donors were used in the study. Monoclonal antibody 166-32 was added to freshly collected, heparinized human blood recirculated in a pediatric cardiopulmonary bypass circuit at a final concentration of 18 microg/mL. An irrelevant monoclonal antibody was used as a negative control with the same donor blood in a parallel bypass circuit on the same day. Blood samples were collected at different time points during recirculation for measurement of activation of complement, neutrophils, and platelets by immunofluorocytometric methods and enzyme-linked immunosorbent assays. RESULTS: Monoclonal antibody 166-32 inhibited the alternative complement activation and the production of Bb, C3a, sC5b-9, and C5a. Upregulation of CD11b on neutrophils and CD62P on platelets was also significantly inhibited by monoclonal antibody 166-32. This is consistent with the inhibition of the release of neutrophil-specific myeloperoxidase and elastase and platelet thrombospondin. The production of proinflammatory cytokine interleukin 8 was also suppressed by the antibody. CONCLUSIONS: The alternative complement cascade is predominantly activated during extracorporeal circulation. Anti-factor D monoclonal antibody 166-32 is effective in inhibiting the activation of complement, neutrophils, and platelets. Inhibition of the alternative complement pathway by targeting factor D could be useful in reducing systemic inflammation in patients undergoing cardiopulmonary bypass.
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In 2000, the responsibility for selecting a DRG variant for use in Germany was assigned to a body comprising representatives of hospitals and insurers called the Self-Administration Board (or Board in this paper). To help the Board, we applied cardiac surgery data from 18 German hospitals to eight different DRG variants. The error caused by bad coding quality could be minimized this way, since all diagnoses and procedures in cardiac surgery must be recorded for quality assurance purposes. To match the German code to the appropriate code required by the DRG variant, we created mapping tables whenever needed. As far as cardiac surgery is concerned, the Australian AR-DRG and the French GHM variants provided the best medical relevance, while the AR-DRG variant considered the level of severity better. Other variants would have to be updated to better reflect the level of medical complexity. Three main causes for wrong grouping could be identified for all systems: incomplete mapping, not enough reference to multidisciplinary treatments, and system construction problems.
We present an efficient parentage control for pigs based on ten polymorphic microsatellite markers analyzed in a single PCR reaction. Assuming one known parent ("paternity control"), combined exclusion probabilities (CEPs) ranged from 99.18% (Landrace), 99.74% (Piétrain) to 99.76% (Large White) for the most important Austrian breeds. Assuming a known parent-pair ("parentage control", e.g. a substituted offspring), the CEP of the 10-plex PCR increased to 99.97% (Landrace) and 99.99% (Piétrain and Large White). We developed an additional standby battery of 5 markers, which might be applied in those cases, where the CEP of the 10-plex PCR is not sufficient. Therefore an automated, cost and time reduced genotype analysis for pigs is available.
OBJECTIVE: To compare the relative efficacy of electroconvulsive therapy (ECT) in psychotic and nonpsychotic patients with unipolar major depression. METHODS: The outcome of an acute ECT course in 253 patients with nonpsychotic (n = 176) and psychotic (n = 77) unipolar major depression was assessed in the first phase of an ongoing National Institute of Mental Health-supported four-hospital collaborative study of continuation treatments after successful ECT courses. ECT was administered with bilateral electrode placement at 50% above the titrated seizure threshold. The remission criteria were rigorous: a score <or=10 on the 24-item Hamilton Rating Scale for Depression (HRSD) after 2 consecutive treatments, and a decrease of at least 60% from baseline. RESULTS: The overall remission rate was 87% for study completers. Among these, patients with psychotic depression had a remission rate of 95% and those with nonpsychotic depression, 83%. Improvement in symptomatology, measured by the HRSD, was more robust and appeared sooner in the psychotic patients compared with the nonpsychotic patients. CONCLUSION: Bilateral ECT is effective in relieving severe major depression. Remission rates are higher and occur earlier in psychotic depressed patients than in nonpsychotic depressed patients. These data support the argument that psychotic depression is a distinguishable nosological entity that warrants separate treatment algorithms.
Flies mutant for the Drosophila homologue of the mammalian transcription factor AP-2 show a severe reduction in leg length and fail to develop joint structures. Presumptive joint cells express dAP-2 in response to Notch signaling. dAP-2 is required for joint cell differentiation and can induce formation of supernumerary joints when misexpressed. Although dAP-2 is expressed only in presumptive joint cells, its activity is required to support cell survival in the entire leg segment. Taken together, our data indicate that dAP-2 is an important mediator of Notch activity in leg development.
As part of a C.O.R.E., multi-site longitudinal study comparing continuation electroconvulsive therapy (ECT) vs. continuation pharmacotherapy, the authors determined the response of 253 patients with major depression to acute-phase, bilateral ECT by use of the 24-item Hamilton Rating Scale for Depression. Remission rates for three age-groups, > or =65 years; 46-64 years; and < or =45 years, were 90 percent, 89.8 percent, and 70 percent, respectively. Age, as a continuous variable, positively influenced response to treatment. Bilateral, dose-titrated ECT is a highly effective acute treatment for major depression, and older age confers a greater likelihood of achieving remission.
Intramuscular fat is an important meat quality trait in pig production. Previously, genetic variants of the heart fatty acid-binding protein (H-FABP) gene and the adipocyte fatty acid-binding protein (A-FABP) gene were suggested to be associated with intramuscular fat content. The objective of this investigation was to study these associations in the three most important Austrian breeding populations (Piétrain, Large White, and Landrace). Restriction fragment length polymorphism analysis of the H-FABP gene revealed a new MspI polymorphic site and genetic variation in all three breeds. Microsatellite analysis of the A-FABP locus showed up to nine different microsatellite alleles segregating. In Austrian breeds, no significant influence of the A-FABP and H-FABP gene polymorphisms on intramuscular fat could be detected. We also evaluated possible associations between the genetic variations at the H-FABP and A-FABP loci and other growth and carcass traits (average daily gain, feed conversion ratio, lean meat content, pH values, meat color, and drip loss). With regard to the extent of the effects, these genetic markers cannot be recommended for selection on growth and carcass traits in Austrian breeding populations.
An analytical method was developed for the determination of bosentan and its three main metabolites in various matrices and species with focus on robustness. The drug assay involved protein precipitation, followed by liquid-liquid extraction and column switching in combination with narrow bore HPLC-MS-MS. Deuterated analogues of the analytes were used as internal standards. The sample preparation procedure was optimised with respect to minimise the suppression effects from different matrices. The drug and its metabolites could be analysed in plasma, serum, bile, and liver samples from man, dog, and rat with a run cycle time of 10 min. The method used always calibration samples made up in human plasma, whereas quality control samples were prepared in human plasma as well as in the identical matrix as the unknown samples. Calibration graphs for the drug and for the metabolites were linear in the range from 1 or 2 to 2000 or 10,000 ng/ml using a sample volume of 0.25 ml. Mean inter-assay precision and accuracy were 3.0% and 98.4%, respectively. Two additional methods were derived from the main method for the analysis of plasma samples only with focus on reduced manual effort and instrumental run cycle time. The modified methods showed a mean inter-assay precision and accuracy of 5.0% and 99.9% for the method using column-switching, and 3.5% and 98.8% for the method using off-line SPE, respectively. All methods proved to be robust, sensitive, and selective during the analysis of several thousand samples.
Chemical-induced carcinogenesis has been in the focus of toxicological research for many decades. However, the mechanisms leading to tumor formation are only understood with certain substances. The intake of potential carcinogens by inhalation is a major route of exposure. Chemical-induced lung tumors are the final manifestation of a multistep pathway, resulting in an imbalance between cell proliferation and cell death by apoptosis. The impact of certain confounding factors e.g. extent of inflammatory response, type of genotoxic event, antagonizing principles and genetic background are discussed in this article. Finally, methods to assess the inflammatory potential of chemicals are referred to.
Co-localization of proteins and nucleic acid sequences by in situ hybridization and immunohistochemistry is frequently difficult as the process necessary to detect the target structure of one technique may negatively affect the target of the other. Morphological impairment may also limit the application of the two techniques on sensitive tissue. To overcome these problems we developed a method to perform in situ hybridization and immunohistochemistry on semithin sections of methyl methacrylate-embedded tissue. Microwave-stimulated antigen retrieval, signal amplification by catalyzed reporter deposition, and fluorescent dyes were used for both techniques, yielding high sensitivity and excellent morphological preservation compared to conventional paraffin sections. Co-localization of in situ hybridization and immunohistochemistry signals with high morphological resolution was achieved on single sections as well as on adjacent multiple serial sections, using computerized image processing. The latter allowed for the co-localization of multiple antigens and a specific DNA sequence at the same tissue level. The method was successfully applied to radiation bone marrow chimeric rats created by transplanting wild-type Lewis rat bone marrow into TK-tsa transgenic Lewis rats, in an attempt to trace and characterize TK-tsa transgenic cells. It also proved useful in the co-localization of multiple antigens in peripheral nerve biopsies.