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Biomedical subjects

W Becker

Publications and source records attributed to W Becker.

At least 55 records · Page 3Linked to original sources

[F-18-FDG hybrid camera PET in patients with postoperative fever].

AIM: Evaluation of F-18-FDG-hybrid-camera-PET imaging in patients with undetermined postoperative fever (POF). METHODS: Prospective study of 18 patients (9 women, 9 men; age 23-85 years) suffering from POF with 2-fluoro-2'-deoxyglucose (F-18-FDG) using a dual headed coincidence camera (DHCC). Surgery had been performed 5-94 days prior to our investigation. 13 of the 18 patients received antibiotic therapy during the time of evaluation. Ten (55%) had an infectious and eight (45%) a non infectious cause of fever. RESULTS: Increased F-18-FDG-uptake outside the surgical wound occurred in 13 regions (infection n = 11, malignancy n = 2). The sensitivity of F-18-FDG-hybrid-camera-PET in imaging infection in areas outside the surgical wound was 86% and the specificity 100%, respectively. Antibiotic therapy did not negatively influence the results of F-18-FDG-scanning. Increased F-18-FDG-uptake within the surgical wound was seen in 8 of 18 patients. The sensitivity of F-18-FDG-hybrid-camera-PET in imaging infection within the surgical wound was 100% and the specificity 56%, respectively. The interval between surgery and F-18-FDG-scanning was significantly shorter in patients with false positive results compared with patients showing true negative results (median 34 vs. 54 days; p = 0.038). CONCLUSION: In POF-Patients, F-18-FDG transaxial tomography performed with a F-18-FDG-hybrid-camera-PET is sensitive in the diagnosis of inflammation and malignant disease within and outside the surgical wound. Because of the accumulation of the tracer both in granulation tissue and infection, the specificity in detecting the focus of fever within the surgical wound is poor.

Adult↗

Radioiodination of monoclonal antibodies, proteins and peptides for diagnosis and therapy. A review of standardized, reliable and safe procedures for clinical grade levels kBq to GBq in the Göttingen/Marburg experience.

Simple and reliable methodologies for radioiodination of proteins and peptides are described. The labeling systems are easy to assemble, capable of radioiodinating any protein or, with slight modifications, also peptide (molecular mass 1000-300,000) from kBq to GBq levels of activity for use in diagnosis and/or therapy. Furthermore, the procedures are feasible in any nuclear medicine department. Gigabecquerel amounts of activity can be handled safely. The most favored iodination methodology relies on the lodogen system, a mild oxidating agent without reducing agents. Thus, protein degradation is minimized. Labeling yields are between 60 and 90%, and immunoreactivities remain > or = 85%. Other radioiodination methods (chloramine-T, Bolton-Hunter) are described and briefly discussed.

Antibodies, Monoclonal↗

Minimal contribution of cell-bound antibodies to the immunoscintigraphy of inflamed joints with 99mTc-anti-CD4 monoclonal antibodies.

AIM: The cellular joint infiltrate in rheumatoid arthritis patients is rich in CD4-positive T-helper lymphocytes and macrophages, rendering anti-CD4 monoclonal antibodies (mAbs) suitable for specific immunoscintigraphy of human/experimental arthritis. Following intravenous injection, however, mAbs are present both in the free form and bound to CD4-positive, circulating monocytes and T-cells. Thus, the present study aimed at analyzing the relative contribution of the free and the cell-bound component to the imaging of inflamed joints in experimental adjuvant arthritis (AA). METHODS: AA rat peritoneal macrophages or lymph node l-cells were incubated in vitro with saturating amounts of 99mTc-anti-CD4 mAb (W3/25) and injected i.v. into rats with AA. RESULTS: In vitro release of 99mTc-anti-CD4 mAb from the cells was limited (on average 1.57%/h for macrophages and 0.84%/h for T-cells). Following i.v. injection, whole body/joint scans and tissue measurements showed only negligible accumulation of radioactivity in inflamed ankle joints (tissue: 0.22 and 0.34% of the injected activity, respectively), whereas the radioactivity was concentrated in liver (tissue: 79% and 71%, respectively), kidney, and urinary bladder. Unlike macrophages, however, anti-CD4 mAb-coated T-cells significantly accumulated in lymphoid organs, the inflamed synovial membrane of the ankle joints, as well as in elbow and knee joints. CONCLUSION: While the overall contribution of cell-bound mAbs to the imaging of arthritic joints with anti-CD4 mAbs is minimal, differential accumulation of macrophages and T-cells in lymphoid organs and the inflamed synovial membrane indicates preferential migration patterns of these 2 cell populations in arthritic rats. Although only validated for 99mTc-anti-CD4 mAbs, extrapolation of the results to other anticellular mAbs with similar affinity for their antigen may be possible.

Animals↗

Sludge management regulations and their applicability in mountainous regions.

The Commission of the European Communities (CEC) is just working out a new directive in order to regulate the agricultural reuse of sewage sludge. This new regulation will also effect a "special case"--sludge usage in a mountainous environment--which will be discussed in this paper. Three reuse sites at small wastewater treatment plants of mountain refuges at altitudes more than 2,000 m a.s.l. are investigated. Applied sludge, soil and drainage flow from lysimeters are analysed. Concerning heavy metal concentrations domestic sewage sludge from these sites differs significantly from municipal sludge. A comparison with background concentrations reveals that no relevant accumulative pollution of the soil is possible. An increase of coliform bacteria of maximum two orders of magnitude is preserved during the long winter period and indicates a limited hygienic risk.

Agriculture↗

The thyroid.

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Humans↗

Chronic bacterial osteomyelitis: prospective comparison of (18)F-FDG imaging with a dual-head coincidence camera and (111)In-labelled autologous leucocyte scintigraphy.

Indium-111-labelled white blood cells ((111)In-WBCs) are currently considered the tracer of choice in the diagnostic work-up of suspected active chronic osteomyelitis (COM). Previous studies in a limited number of patients, performed with dedicated PET systems, have shown that [(18)F]2'-deoxy-2-fluoro- D-glucose (FDG) imaging may offer at least similar diagnostic accuracy. The aim of this prospective study was to compare FDG imaging with a dual-head coincidence camera (DHCC) and (111)In-WBC imaging in patients with suspected COM. Thirty consecutive non-diabetic patients with possible COM underwent combined skeletal scintigraphy (30/30 patients), (111)In-WBC imaging (28/30 patients) and FDG-PET with a DHCC (30/30 patients). During diagnostic work-up, COM was proven in 11/36 regions of suspected skeletal infection and subsequently excluded in 25/36 regions. In addition, soft tissue infection was present in five patients and septic arthritis in three. (111)In-WBC imaging in 28 patients was true positive in 2/11 regions with proven COM and true negative in 21/23 regions without further evidence of COM. False-positive results occurred in two regions and false-negative results in nine regions suspected for COM. Most of the false-negative results (7/9) occurred in the central skeleton. If the analysis was restricted to the 18 regions with available histology ( n=17) or culture ( n=1), (111)In-WBC imaging was true positive in 2/18 regions, true negative in 8/18 regions, false negative in 7/18 regions and false positive in 1/18 regions. FDG-DHCC imaging was true positive in 11/11 regions with proven COM and true negative in 23/25 regions without further evidence of COM. False-positive results occurred in two regions. If the analysis was restricted to the 19 regions with available histology ( n=18) or culture ( n=1), FDG-DHCC imaging was true positive in 9/9 regions with proven COM and true negative in 10/10 regions without further evidence of COM. It is concluded that FDG-DHCC imaging is superior to (111)In-WBC scintigraphy in the diagnosis of COM in the central skeleton and therefore should be considered the method of choice for this indication. This seems to hold true for peripheral lesions as well, but in our series the number of cases with proven infection was too small to permit a final conclusion.

Adult↗

Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A.

Protein kinases of the DYRK ('dual-specificity tyrosine-regulated kinase') family are characterized by a conserved Tyr-Xaa-Tyr motif (Tyr-319-Tyr-321) in a position exactly corresponding to the activation motif of the mitogen-activated protein kinase (MAP kinase) family (Thr-Xaa-Tyr). In a molecular model of the catalytic domain of DYRK1A, the orientation of phosphorylated Tyr-321 is strikingly similar to that of Tyr-185 in the known structure of the activated MAP kinase, extracellular-signal-regulated kinase 2. Consistent with our model, substitution of Tyr-321 but not of Tyr-319 by phenylalanine markedly reduced the enzymic activity of recombinant DYRK1A expressed in either Escherichia coli or mammalian cells. Direct identification of phosphorylated residues by tandem MS confirmed that Tyr-321, but not Tyr-319, was phosphorylated. When expressed in COS-7 cells, DYRK1A was found to be fully phosphorylated on Tyr-321. A catalytically inactive mutant of DYRK1A contained no detectable phosphotyrosine, indicating that Tyr-321 is autophosphorylated by DYRK1A. MS identified Tyr-111 and Ser-97 as additional autophosphorylation sites in the non-catalytic N-terminal domain of bacterially expressed DYRK1A. Enzymic activity was not affected in the DYRK1A-Y111F mutant. The present experimental data and the molecular model indicate that the activity of DYRK1A is dependent on the autophosphorylation of a conserved tyrosine residue in the activation loop.

Animals↗

Feynman's path-integral approach for intense-laser-atom interactions.

Atoms interacting with intense laser fields can emit electrons and photons of very high energies. An intuitive and quantitative explanation of these highly nonlinear processes can be found in terms of a generalization of classical Newtonian particle trajectories, the so-called quantum orbits. Very few quantum orbits are necessary to reproduce the experimental results. These orbits are clearly identified, thus opening the way for an efficient control as well as previously unknown applications of these processes.

Journal Article↗

The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site.

Forkhead in rhabdomyosarcoma (FKHR) is a transcription factor that has been implicated in the control of gene expression by insulin, as well as the regulation of apoptosis by survival factors. These signals trigger the protein kinase B (PKB)-catalysed phosphorylation of FKHR at three residues (Thr(24), Ser(256) and Ser(319)) by a phosphoinositide 3-kinase-dependent pathway that results in the nuclear exit and inactivation of this transcription factor. Here, we have identified a conserved residue (Ser(329)) as a novel in vivo phosphorylation site on FKHR. Ser(329) phosphorylation also decreases the ability of FKHR to stimulate gene transactivation and reduces the proportion of FKHR present in the nucleus. However, unlike the residues targetted by PKB, Ser(329) is phosphorylated in unstimulated HEK-293 cells, and phosphorylation is not increased by stimulation with insulin-like growth factor-1 or by transfection with 3-phosphoinositide-dependent protein kinase-1. We have also purified a protein kinase to near homogeneity from rabbit skeletal muscle that phosphorylates FKHR at Ser(329) specifically and identified it as DYRK1A (dual-specificity tyrosine-phosphorylated and regulated kinase 1A). We find that FKHR and DYRK1A co-localize in discrete regions of the nucleus and can be co-immunoprecipitated from cell extracts. These experiments suggest that DYRK1A may phosphorylate FKHR at Ser(329) in vivo.

Amino Acid Sequence↗

The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase.

The substrate specificity of glycogen synthase kinase 3 (GSK3) is unusual in that efficient phosphorylation only occurs if another phosphoserine or phosphothreonine residue is already present four residues C-terminal to the site of GSK3 phosphorylation. One such substrate is the epsilon-subunit of rat eukaryotic protein-synthesis initiation factor 2B (eIF2Bepsilon), which is inhibited by the GSK3-catalysed phosphorylation of Ser(535). There is evidence that GSK3 is only able to phosphorylate eIF2Bepsilon at Ser(535) if Ser(539) is already phosphorylated by another protein kinase. However, no protein kinases capable of phosphorylating Ser(539) have so far been identified. Here we show that Ser(539) of eIF2Bepsilon, which is followed by proline, is phosphorylated specifically by two isoforms of dual-specificity tyrosine phosphorylated and regulated kinase (DYRK2 and DYRK1A), but only weakly or not at all by other 'proline-directed' protein kinases tested. We also establish that phosphorylation of Ser(539) permits GSK3 to phosphorylate Ser(535) in vitro and that eIF2Bepsilon is highly phosphorylated at Ser(539) in vivo. The DYRK isoforms also phosphorylate human microtubule-associated protein tau at Thr(212) in vitro, a residue that is phosphorylated in foetal tau and hyperphosphorylated in filamentous tau from Alzheimer's-disease brain. Phosphorylation of Thr(212) primes tau for phosphorylation by GSK3 at Ser(208) in vitro, suggesting a more general role for DYRK isoforms in priming phosphorylation of GSK3 substrates.

Animals↗

[The iodine supply of newborns. Comparison of iodine absorption and iodine excretion of mother and child].

BACKGROUND: Since 1989 the use of iodized salt has been allowed in Germany, additional supplementation with iodide tablets has been recommended during pregnancy and lactation. This study was undertaken to clarify whether the iodine intake of neonates and young infants improved since then. PATIENTS AND METHODS: In the first part of the study the urinary iodine excretion of 52 newborns and their mothers in 1998 was compared to data of similar studies 1983 in the area of Göttingen and 1982 in the areas of Heidelberg and Rothenburg, Germany. All these are geographically low-iodine areas. In the second part the iodine supply of infants in 1998-1999 under feeding with mother's milk or formulas in 1998 and 1999 was obtained by measuring iodide concentrations in urine and milk using a high pressure liquid chromatography (HPLC) method. RESULTS: 45% of pregnant women were without iodide supplementation in 1998. In 1998 the median urinary iodide concentration during the first week of life was 4.3 micrograms/dl, which was more than twice that found in 1983 (1.75 micrograms/dl). Infants feeding by mother's milk without maternal iodine supplementation or by semi-elementary diet had the lowest urinary iodine excretion, whereas significantly higher values were measured when feeding formulas for term or preterm infants. CONCLUSIONS: The iodine intake of newborns has markedly improved during 15 years. The WHO criterias for adequate iodine supply (TSH < 5 microU/ml and urinary iodine >/ = 10 micrograms/dl) were only partly fulfilled in Göttingen indicating that a mild iodine deficiency still exists with the risk of iodine deficiency disorders.

Bottle Feeding↗

[Parosteal lipoma].

Paraosteal lipoma is a rare benign tumour of the musculoskeletal system. It's features consist of a fatty component seated on a hypersotosis i.e. an exostose-like bone prominence. This tumor has a high tendency of metaplasia. Therefore chondroid elements may be present in addition to the fatty and bony components. Therapy of choice is complete surgical removal including the hyperostosis. Presenting this case the clinical and morphological characteristic of this rare tumour are discussed.

Adult↗

Perception of angular head position during attempted alignment with eccentric visual objects.

The perception of angular head position with respect to a visual object was investigated using three different methods: Pointer indication (P); in the dark, subjects' (Ss') heads were horizontally turned to various positions (range +/- 54 degrees); Ss then rotated a pointer carrying a light emitting diode (LED) so as to align it with head position. Active head pointing (A); again in darkness, the pointer was rotated to various positions; Ss then turned their heads so as to align them with the pointer. Reading from visible scale (V); Ss viewed a degrees scale on a circular screen; Ss' heads were turned as in P, and Ss reported head position in terms of this scale. The results obtained with all three methods indicate that head position is overestimated with respect to the visual object (LED, scale mark): object position exceeded head position by 6, 18, and 7% when measured with the P-, A-, and V-methods, respectively (median values). The observed misalignment between head and object suggests that subjective primary eye position is shifted in the direction of head rotation by a cross-talk of head position. Whether a functional advantage or merely a tolerated side-effect of other constraints, this behavior confers the impression of looking "straight ahead" in the literal sense when gaze is shifted by coordinated eye-head movements with a 10% eye and a 90% head share in total lateral displacement. In an attempt to probe a hypothesized internal representation of head position implied in head-to-object alignment, Ss were also to estimate head position in space using only neck proprioceptive information. In complete darkness, responses were often non-linear functions of head position with overestimation of large eccentricities. When a head-centered LED was added (which conveyed no position information), responses became more linear, suggesting that the mere presence of visual afferents may improve the perceptual interpretation of proprioceptive information.

Darkness↗

Visual object localisation in space. Interaction of retinal, eye position, vestibular and neck proprioceptive information.

Perceptual updating of the location of visual targets in space after intervening eye, head or trunk movements requires an interaction between several afferent signals (visual, oculomotor efference copy, vestibular, proprioceptive). The nature of the interaction is still a matter of debate. To address this problem, we presented subjects (n=6) in the dark with a target (light spot) at various horizontal eccentricities (up to +/-20 degrees ) relative to the initially determined subjective straight-ahead direction (SSA). After a memory period of 12 s in complete darkness, the target reappeared at a random position and subjects were to reproduce its previous location in space using a remote control. For both the presentation and the reproduction of the target's location, subjects either kept their gaze in the SSA (retinal viewing condition) or fixated the eccentric target (visuo-oculomotor). Three experimental series were performed: A, "visual-only series": reproduction of the target's location in space was found to be close to ideal, independently of viewing condition; estimation curves (reproduced vs presented positions) showed intercepts approximately 0 degrees and slopes approximately 1; B, "visual-vestibular series": during the memory period, subjects were horizontally rotated to the right or left by 10 degrees or 18 degrees at 0.8-Hz or 0.1-Hz dominant frequency. Following the 0.8-Hz body rotation, reproduction was close to ideal, while at 0.1 Hz it was partially shifted along with the body, in line with the known vestibular high-pass characteristics. Additionally, eccentricity of target presentation reduced the slopes of the estimation curves (less than 1); C, "visual-vestibular-neck series": a shift toward the trunk also occurred after low-frequency neck stimulation (trunk rotated about stationary head). When vestibular and neck stimuli were combined (independent head and trunk rotations), their effects summed linearly, such that the errors cancelled each other during head rotation on the stationary trunk. Variability of responses was always lowest for targets presented at SSA, irrespective of intervening eye, head or trunk rotations. We conclude that: (1) subjects referenced "space" to pre-rotatory SSA and that the memory trace of the target's location in space was not altered during the memory period; and that (2) they used internal estimates of eye, head and trunk displacements with respect to space to match current target position with the memory trace during reproduction; these estimates would be obtained by inverting the physical coordinate transformations produced by these displacements. We present a model which is able to describe these operations and whose predictions closely parallel the experimental results. In this model the estimate of head rotation in space is not obtained directly from the vestibular head-in-space signal, but from a vestibular estimate of the kinematic state of the body support.

Adult↗

Somatostatin receptor scintigraphy in the management of cerebral malignant ectomesenchymoma: a case report.

A 10-year-old girl presented with a cerebral malignant ectomesenchymoma (MEM), a very unusual tumour with undifferentiated mesenchymal as well as ectodermal elements. Somatostatin receptor scintigraphy (SRS) was performed during the diagnostic workup. The recurrent residual tumour mass was exactly visualized with SRS, and was negative after successful treatment of the patient. The potential application of SRS in initial staging, follow-up and therapy planning in MEM is discussed. This is the first application of SRS in MEM.

Brain Neoplasms↗