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Hans-Joachim Wagner

Publications and source records attributed to Hans-Joachim Wagner.

At least 19 recordsLinked to original sources

Distribution of phosphorylated protein kinase C alpha in goldfish retinal bipolar synaptic terminals: control by state of adaptation and pharmacological treatment.

Protein kinase C (PKC) is a signalling enzyme critically involved in many aspects of synaptic plasticity. In cyprinid retinae, the PKC alpha isoform is localized in a subpopulation of depolarizing bipolar cells that show adaptation-related morphological changes of their axon terminals. We have studied the subcellular localization of phosphorylated PKC alpha (pPKC alpha) in retinae under various conditions by immunohistochemistry with a phosphospecific antibody. In dark-adapted retinae, pPKC alpha immunoreactivity is weak in the cytoplasm of synaptic terminals, labelling being predominantly associated with the membrane compartment. In light-adapted cells, immunoreactivity is diffusely distributed throughout the terminal. Western blot analysis has revealed a reduction of pPKC alpha immunoreactivity in cytosolic fractions of homogenized dark-adapted retinae compared with light-adapted retinae. Pharmacological experiments with the isoform-specific PKC blocker Goe6976 have shown that inhibition of the enzyme influences immunolabelling for pPKC alpha, mimicking the effects of light on the subcellular distribution of immunoreactivity. Our findings suggest that the state of adaptation modifies the subcellular localization of a signalling molecule (PKC alpha) at the ribbon-type synaptic complex. We propose that changes in the subcellular distribution of PKC alpha immunoreactivity might be one component regulating the strength of the signal transfer of the bipolar cell terminal.

Adaptation, Ocular↗

The impact of the dosage of intravenous gadolinium-chelates on the vascular signal intensity in MR angiography.

To show the effects of different concentrations of contrast agent on signal time curves and image contrast of abdominal aorta, vena cava and portal vein in comparison to each other as well as liver and spleen. Imaging was carried out in a 1.0 Tesla clinical scanner. Sixty patients were prospectively included and divided into three contrast agent (Gd-DTPA) dosage groups (0.1 mmol/kg, 0.2 mmol/kg and 0.3 mmol/kg). All patients were scanned using a time-resolved 3D FLASH sequence (58 phases) with a 3.75 second acquisition time per phase. Signal time curves and image contrast levels were evaluated. No significant differences were found for the maximum signal enhancement between the groups in the investigated vessels. Image masking, the subtraction of the baseline images, resulted in a substantial improvement in image contrast. However, statistically significant differences between the contrast agent dosage groups could only be found for vena cava and liver. Vessel conspicuity is not significantly improved with an increase of contrast agent dose. However, an increase in contrast agent dosage increases vessel contrast. Our findings suggest that a single dose single station investigation seems to be sufficient for high quality abdominal MRA.

Adult↗

Regulation of GluR1 abundance in murine hippocampal neurones by serum- and glucocorticoid-inducible kinase 3.

Phosphatidylinositol 3 kinase (PI3-kinase) is activated during and is required for hippocampal glutamate receptor-dependent long-term potentiation. It mediates the delivery of AMPA receptors to the neuronal surface. Among the downstream targets of PI3-kinase are three members of the serum- and glucocorticoid-inducible kinase family, SGK1, SGK2 and SGK3. In Xenopus oocytes expressing the AMPA subunit GluR1, we show that SGK3, and to a lesser extent SGK2, but not SGK1, increase glutamate-induced currents by increasing the abundance of GluR1 protein in the cell membrane. We further show Sgk3 mRNA expression in the hippocampus by RT-PCR and in situ hybridization. According to Western blotting, the hippocampal abundance of GluR1 is significantly lower in gene-targeted mice lacking SGK3 (Sgk3-/-) than in their wild-type littermates (Sgk3+/+). The present observations disclose a novel mechanism in the regulation of GluR1.

Animals↗

Glucocorticoid adrenal steroids and glucocorticoid-inducible kinase isoforms in the regulation of GluR6 expression.

Generation of memory is enhanced during stress, an effect attributed to stimulation of neuronal learning by adrenal glucocorticoids. The glucocorticoid-dependent genes include the serum- and glucocorticoid-inducible kinase SGK1. SGK1 is activated through the phosphatidylinositol 3 kinase (PI3-kinase) pathway by growth factors such as insulin-like growth factor-1 (IGF1) or tumour growth factor beta (TGF-beta). Previously, a fourfold higher expression of SGK1 has been observed in fast-learning rats as compared with slow-learning rats. The mechanisms linking glucocorticoids or SGK1 with neuronal function have, however, remained elusive. We show here that treatment of mice with the glucocorticoid dexamethasone (238 microg day-1 for 8-20 days) enhances hippocampal expression of GluR6. Immunohistochemistry reveals significantly enhanced GluR6 protein abundance at neurones but not at astrocytes in mice. Immunohistochemistry and patch clamp on hippocampal neurones in primary culture reveal upregulation of GluR6 protein abundance and kainate-induced currents following treatment with dexamethasone (1 microm) and TGF-beta (1 microm). In Xenopus oocytes expressing rat GluR6, coexpression of SGK1 strongly increases glutamate-induced current at least partially by increasing the abundance of GluR6 protein in the plasma membrane. The related kinases SGK2 and SGK3 similarly stimulate GluR6, but are less effective than SGK1. The observations point to a novel mechanism regulating GluR6 which contributes to the regulation of neuronal function by glucocorticoids.

Animals↗

The organization of the inner retina in a pure-rod deep-sea fish.

The pure rod retina of a deep-sea eel species was used as a model system for the study of the differentiation of horizontal, bipolar, amacrine and ganglion cells. We wanted to test the hypothesis that the functional organization of the inner retina is less complex than in species with duplex, rod- and cone-containing retinae. We used immunocytochemistry, backfilling ganglion cells with fluorescent dextranes and microinjection of Lucifer Yellow, to visualize the micromorphology of the various cell types in a confocal microscope. The pure rod retina contains a single type of horizontal cell. The inner plexiform layer is 10-15 microm thick and shows three main sublayers. Bipolar terminals are found in all sublayers, but the majority are found in the inner sublamina b (PKC-immunoreactive cells, that in fish with duplex retinae receive a mixed rod-cone input). The neurochemical diversity of amacrine cells in terms of immunoreactivity does not differ from other teleosts; this similarity includes the pattern of dendritic stratification and ramification as revealed by microinjection. Ten different types of ganglion cells are distinguished based on the sizes of their perikaryon and dendritic field, and the stratification pattern in the inner plexiform layer. This is similar to the situation in catfish with retinae containing a single type of cone in addition to a majority of rods. In this respect, the differences between pure rod retinae and duplex retinae containing a single cone type were less obvious than hypothesized. In the deep-sea eel, the density of dendritic ramification in amacrine and ganglion cells was strongly reduced. This may be functionally related to the fact that vision in the deep sea environment relies exclusively on bioluminescence and is represented by burst-like emissions of point sources. This requires a mode of retinal signal processing that is less complex than in duplex retinae and involves a lower density of dendritic branching and synapses.

Animals↗

Adaptive plasticity during the development of colour vision.

Colour vision greatly enhances the discriminatory and cognitive capabilities of visual systems and is found in a great majority of vertebrates and many invertebrates. However, colour coding visual systems are confronted with the fact that the external stimuli are ambiguous because they are subject to constant variations of luminance and spectral composition. Furthermore, the transmittance of the ocular media, the spectral sensitivity of visual pigments and the ratio of spectral cone types are also variable. This results in a situation where there is no fixed relationship between a stimulus and a colour percept. Colour constancy has been identified as a powerful mechanism to deal with this set of problems; however, it is active only in a short-term time range. Changes covering longer periods of time require additional tuning mechanisms at the photoreceptor level or at postreceptoral stages of chromatic processing. We have used the trichromatic blue acara (Aequidens pulcher, Cichlidae) as a model system and studied retinal morphology and physiology, and visually evoked behaviour after rearing fish for 1-2 years under various conditions including near monochromatic lights (spectral deprivation) and two intensities of white light (controls). In general, long-term exposure to long wavelengths light had lesser effects than light of middle and short wavelengths. Within the cone photoreceptors, spectral deprivation did not change the absorption characteristics of the visual pigments. By contrast, the outer segment length of middle and long-wave-sensitive cones was markedly increased in the blue rearing group. Furthermore, in the same group, we observed a loss of 65% short-wave-sensitive cones after 2 years. These changes may be interpreted as manifestations of compensatory mechanisms aimed at restoring the balance between the chromatic channels. At the horizontal cell level, the connectivity between short-wave-sensitive cones and the H2 cone horizontal cells, and the spinule dynamics were both affected in the blue light group. This observation rules out the role of spinules as sites of chromatic feedback synapses. The light-evoked responses of H2 horizontal cells were also sensitive to spectral deprivation showing a shift of the neutral point towards short wavelengths in the blue rearing group. Interestingly, we also found an intensity effect because in the group reared in bright white light the neutral point was more towards longer wavelength than in the dim light group. Like the changes in the cones, the reactions of horizontal cells to spectral deprivation in the long wave domain can be characterised as compensatory. We also tested the spectral sensitivity of the various experimental groups of blue acara in visually evoked behaviour using the optomotor response paradigm. In this case, the changes in the relative spectral sensitivity were more complex and could not be explained by a simple extrapolation of the adaptive and compensatory processes in the outer retina. We conclude that the inner retina, and/or the optic tectum are also involved and react to the changes of the spectral environment. In summary, we have shown a considerable developmental plasticity in the colour vision system of the blue acara, where epigenetic adaptive processes at various levels of the visual system respond to the specific spectral composition of the surroundings and provide a powerful mechanism to ensure functional colour vision in different visual environments. We suggest that processes involving an active fine-tuning of the photoreceptors and the postreceptoral processing of chromatic information during ontogenetic development are a general feature of all colour vision systems. Such mechanisms would establish a functional balance between the various chromatic channels. This appears to be an essential condition for the cognitive systems to extract the relevant and stable information from the unstable and changing stimulus situation.

Adaptation, Ocular↗

Cellular immunity to Epstein-Barr virus in liver transplant recipients treated with rituximab for post-transplant lymphoproliferative disease.

The evaluation of long-term cellular immunity to EBV in pediatric orthotopic liver transplant (OLT) recipients after treatment with the humanized anti-CD20 monoclonal antibody (Rituximab) has not yet been explored. At our institution, one child with EBV-related mononucleosis-like syndrome and five children with polymorphic-EBV-PTLD occurring 6-88 months after OLT were treated with Rituximab. Treatment was well tolerated. All children achieved complete remission. After Rituximab, B-lymphocytes were undetectable in the peripheral blood and EBV-load, monitored with real-time PCR, decreased to undetectable levels in all children from >4000 copies/microg DNA at diagnosis. Four to eight months after Rituximab, EBV-load increased (>4000 copies/microg DNA) in four children, and PTLD recurred in three. Their frequency of EBV-specific T-cell precursors, measured by Elispot analysis, remained lower than in healthy controls. Rituximab effectively induced regression of PTLD in OLT recipients. However, EBV-specific T-cell immunocompetence, which may be crucial for the long-term control of EBV-mediated proliferation, did not improve.

Antibodies, Monoclonal↗

On the prehistory of the German Society of Legal Medicine.

The paper gives a review on the foundation of local associations of legal medicine and their journals at the beginning and in the mid of the 19th century in Germany before the German Society of Legal Medicine was founded.

Forensic Medicine↗

Peripheral blood lymphocytes express recombination-activating genes 1 and 2 during Epstein-Barr virus-induced infectious mononucleosis.

Implicit in the persistence of Epstein-Barr virus (EBV) in B lymphocytes is the successful circumvention of ongoing cell selection for competence of B cell receptors (BCRs). Because the EBV infection of B cells in vitro induces enzymatic machinery that is responsible for secondary immunoglobulin gene rearrangement, we examined the expression of the recombination-activating genes (RAGs) in peripheral blood mononuclear cells (PBMCs) from 26 patients with infectious mononucleosis (IM). RAG1 and/or RAG2 RNA was detected in PBMCs from 42% of patients with IM but not from healthy control subjects. EBV may usurp the cellular mechanism that diversifies the BCR, to guarantee a level of survival signaling sufficient for its own persistence.

Adolescent↗

Treatment of benign tracheal stenosis utilizing self-expanding nitinol stents.

We assessed the results of self-expanding metallic stent insertion into benign proximal tracheal stenosis in patients not appropriate or unfit for surgical repair. Proximal benign tracheal stenoses had occurred in 11 patients (7 men, 4 women, mean age 68.8 years) after long-time intubation (n = 6), tracheostomy (n = 4), or chondropathia (n = 1). Fourteen self-expanding nitinol stents were placed in the patients under general anesthesia with endoscopical and fluoroscopical guidance. Stent insertion was successful in all cases and led to immediate relief of the morphological and functional airway obstruction. No immediate complications were noted. During the mean follow-up period of 67.5 weeks we observed one recurrent dyspnea 3 months after implantation and granuloma formation at the stent insertion site in another patient. Both complications were successfully treated with additional stent insertion in one case and laser resection of granulomas in the other. Self-expanding nitinol stents should be considered for the treatment of benign proximal tracheal obstruction in selected patients for whom surgical repair is contraindicated.

Adult↗

Prompt versus preemptive intervention for EBV lymphoproliferative disease.

Posttransplantation lymphoproliferative disorders (PTLDs) caused by uncontrolled expansion of Epstein-Barr virus (EBV)-infected B cells after hematopoietic stem cell transplantation (HSCT) can be predicted by an increase in EBV DNA in peripheral blood mononuclear cells. We used real-time quantitative polymerase chain reaction (RQ-PCR) analysis to determine whether frequent monitoring of EBV DNA to allow preemptive treatment is truly of value in patients after HSCT. More than 1300 samples from 85 recipients were analyzed. No patient with consistently low EBV DNA levels developed PTLD. Nine patients had a single episode with a high EBV load (more than 4000 EBV copies/microg peripheral blood mononuclear cell [PBMC] DNA), and 16 patients had high EBV loads detected on 2 or more occasions. Only 8 of these developed symptoms consistent with PTLD, and all were promptly and successfully treated with EBV-specific cytotoxic T cells or CD20 monoclonal antibody. Hence, quantitative measurement of EBV DNA may best be used to enable the prompt rather than the preemptive treatment of PTLD.

Adoptive Transfer↗

[Interventional therapy of peripheral arterial disease-potentials and limitations].

The technical success rate of endovascular interventions in order to improve perfusion in peripheral arterial disease in the lower extremities has been markedly improved in the last decade due to clinical application of new recanalization techniques like application of hydrophil-coated guide wires, implantation of stents or stent grafts. If the-even long-segment-obstruction can be recanalized, the interventional radiologist is able to open the arterial vessel sufficiently. The excellent immediate results are limited in the long term by recurrent stenoses, which appear in different rates according to the vascular region. Whereas recurrent stenoses have nearly no clinical significance in the aortoiliac vascular segment due to the size of the treated vessels and the excellent flow, there is a significant amount of restenoses in the femoropopliteal segment and, even more, in the tibial arteries. This leads to a different indication of endovascular therapy according to the segment treated. However, in an interdisciplinary consensus we offer primary endovascular therapy for treatment of aortoiliac obstruction to all patients, whereas lesions at the femoral bifurcation are a clear primary indication for open surgical treatment. In the femoropopliteal segment, we choose a primary endovascular procedure with respect to the length of the occlusion, patient's risk factors and comorbidities. Yet, longer obstructions are a clear indication for primary surgical treatment. In cases of infrapopliteal disease, we recommend an endovascular treatment as the initial option due to the reduced invasiveness of the predominantly old and multimorbid patient cohort. Further clinical research for the evaluation of endovascular therapeutic measures in peripheral arterial disease urgently requires outcome studies, which include clinically relevant endpoints to better define the clinical value of endovascular therapy compared to traditional surgical bypass procedures. Until new clinical trials will be published, the Transatlantic Consensus document (TASC) of a variety of vascularly specialized scientific societies seems to be a helpful guideline.

Angiography↗

Effects of altering infusion parameters on intimal hyperplasia following local catheter-based delivery into the rabbit iliac artery.

BACKGROUND: Efficient local gene or drug therapy requires optimized application modalities to avoid vessel damage, which might lead to increased neointimal hyperplasia. Aim of the study was to evaluate different application parameters for local delivery using the channeled balloon catheter in order to minimize vessel trauma induced by local application. METHODS AND RESULTS: Sixty cholesterol fed rabbits were randomly enrolled into twelve groups of different local application parameters: group I, application pressure 2atm/application volume 1ml physiologic saline; group II, 2atm/2ml; group III, 2atm/5ml; group IV, 4atm/1ml; group V, 4atm/2ml; group VI, 4atm/5ml. The other six groups received Ringer's solution instead of saline. Administration of the solution was randomly performed in one iliac artery using the channeled balloon catheter with simultaneous balloon angioplasty (8atm). The contralateral iliac artery served as a control and was treated with balloon angioplasty only. Four weeks after local therapy, calibrated angiography was performed; the animals were sacrificed, vessel segments were excised and quantitative morphometric measurements were obtained. In none of the animals acute complications, e.g. dissection, thrombosis or perforation of the vessel, was noted. Up to an application pressure of 4atm and an application volume of 5ml, no significant neointima formation was seen compared to arteries which underwent angioplasty only. Additionally, no significant differences between saline and Ringer's solution were detected. In a multivariate analysis, neither application pressure nor volume were found to have a statistically significant influence on the amount of neointimal hyperplasia. CONCLUSIONS: Local application of "drugs" using the channeled balloon catheter is safe and feasible without significant induction of neointimal hyperplasia compared to angioplasty, if an application volume of 5ml and a pressure of 4atm is not exceeded.

Angiography↗

A strategy for treatment of Epstein-Barr virus-positive Hodgkin's disease by targeting interleukin 12 to the tumor environment using tumor antigen-specific T cells.

Adoptive immunotherapy with Epstein-Barr virus (EBV)-specific cytotoxic T cells (CTL) is effective for the prophylaxis and treatment of EBV-induced lymphoma in hematopoietic stem cell recipients. However, in EBV-positive Hodgkin's disease (HD) the efficacy of adoptively transferred EBV-specific CTL may be limited by tumor-derived immunosuppressive factors, such as T-cell growth factor (TGF) beta, interleukin (IL)13 and the chemokine TARC. Local delivery of IL12 to tumor sites by tumor-specific CTL could provide direct antitumor effects and overcome the CTL-inhibitory effects of the Th2 tumor environment while avoiding the systemic toxicity of recombinant IL12. EBV-specific CTL transduced with a retrovirus vector expressing the p40 and p35 subunits of IL12 as a single molecule (Flexi-IL12), produced IL12 following antigenic stimulation. This resulted in an elevated production of Th1 cytokines, including interferon gamma and tumor necrosis factor alpha, and a reduction in the Th2 cytokines IL4 and IL5. Flexi-IL12-transduced CTL resisted the antiproliferative and anticytotoxic effects of exogenous TGFbeta, likely by antagonizing the TGFbeta-induced downregulation of the Th1 transcriptional factor T-bet. In addition, Flexi-IL12-transduced CTL demonstrated a proliferative advantage in the presence of inhibitory supernatants from HD-derived cell lines. Tumor-specific, Flexi-IL12-transduced EBV-specific CTL should have a functional advantage over unmodified CTL, particularly in the presence of the adverse Th2 cytokine environment produced by Hodgkin tumor cells.

Antigens, Neoplasm↗

Pancreatic transplants: noninvasive evaluation with secretin-augmented mr pancreatography and MR perfusion measurements--preliminary results.

Feasibility of secretin-augmented magnetic resonance (MR) pancreatography and dynamic contrast material-enhanced MR measurements for evaluation of functional status of pancreatic allografts was determined by quantifying the excretion and perfusion of the grafts. Ten patients were included prospectively before pancreatic transplantation. Dynamic T2-weighted sequences after secretin stimulation and dynamic contrast-enhanced T1-weighted gradient-echo sequences were performed. Area under the curve and maximum signal intensity-to-time ratio were determined in selected regions of interest. Biochemical parameters, Doppler ultrasonography, and/or surgery were standards for final diagnosis. Patients with normal outcome (n = 7) produced 236 mL +/- 104 (standard deviation) of pancreatic juice, and patients with dysfunctional grafts (n = 3) produced 42 mL +/- 25. Area under the curve and maximum signal intensity-to-time ratio provided thresholds of 0.5 and 0.3, respectively, for distinction between functional and dysfunctional grafts. Secretin-augmented MR pancreatography combined with MR perfusion measurements may aid in differentiation between patients with and those without graft dysfunction.

Adult↗

Displaced amacrine cells disappear from the ganglion cell layer in the central retina of adult fish during growth.

PURPOSE: Fish grow throughout life, including enlargement of eye and retina. Retinal growth involves several mechanisms of adjustment, such as cell addition and dendritic growth. To discover possible other means with which the animals adjust to changing eye size, the distribution of displaced amacrine cells (DACs) and ganglion cells (GCs) was analyzed in the retina of three sizes of a South American cichlid, the blue arcara Aequidens pulcher. METHODS: DACs were identified by staining with antibodies specific for the calcium-binding protein parvalbumin. They were also weakly positive for staining against choline acetyl transferase (ChaT). GCs were labeled retrogradely with rhodamine dextran. Densities for both DACs and GCs were lower in the retinas of large fish. To distinguish changes due to eye size from specific adjustments, the proportions of DACs to GCs were examined, rather than the absolute cell densities, in various retinal regions in cryostat sections and wholemount preparations from fish of the three sizes. RESULTS: The analyses suggest that, in small and large fish, DACs and GCs were produced in similar proportions (ratio of DACs to GCs, approximately 0.62) in the retinal periphery where new retinal tissue was added by the germinal zone. However, in the central retina of large fish, this proportion was shifted toward GCs (DAC-GC ratio as low as 0.25). CONCLUSIONS: During growth of the eye, the proportion of DACs in the ganglion cell layer decreases, indicating that these cells are eliminated from the ganglion cell layer by some unknown mechanism.

Amacrine Cells↗

Pineal organs of deep-sea fish: photopigments and structure.

We have examined the morphology and photopigments of the pineal organs from a number of mesopelagic fish, including representatives of the hatchet fish (Sternoptychidae), scaly dragon-fish (Chauliodontidae) and bristlemouths (Gonostomidae). Although these fish were caught at depths of between 500 and 1000 m, the morphological organisation of their pineal organs is remarkably similar to that of surface-dwelling fish. Photoreceptor inner and outer segments protrude into the lumen of the pineal vesicle, and the outer segment is composed of a stack of up to 20 curved disks that form a cap-like cover over the inner segment. In all species, the pineal photopigment was spectrally distinct from the retinal rod pigment, with lambdamax displaced to longer wavelengths, between approximately 485 and 503 nm. We also investigated the pineal organ of the deep demersal eel, Synaphobranchus kaupi, caught at depths below 2000 m, which possesses a rod visual pigment with lambdamax at 478 nm, but the pineal pigment has lambdamax at approximately 515 nm. In one species of hatchet fish, Argyropelecus affinis, two spectral classes of pinealocyte were identified, both spectrally distinct from the retinal rod photopigment.

Animals↗