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H-J Wagner

Publications and source records attributed to H-J Wagner.

22 records · Page 2Linked to original sources

Expansion of EBV latent membrane protein 2a specific cytotoxic T cells for the adoptive immunotherapy of EBV latency type 2 malignancies: influence of recombinant IL12 and IL15.

BACKGROUND: EBV-associated malignancies with a Type II latency gene expression pattern, such as EBV-positive HD, or nasopharyngeal carcinoma, frequently express the EBV latency Ag LMP2a. Hence, they provide a potential target for adoptive immunotherapy using in vitro-generated LMP2a-specific cytotoxic T lymphocytes (CTL). In this study, LMP2a-specific CTL were specifically amplified and the influence of rIL12 and rIL15 on the culture outcome was tested. METHODS: PBMC from donors were stimulated twice with autologous DC transduced with an adenovirus vector expressing LMP2a. This led to a significant expansion of LMP2a-tetramer-specific CTL, which were subsequently further expanded with autologous EBV-transformed B-lymphoblastoid cells (LCL). The addition of rIL12 and rIL15 to the standard IL2-containing culture medium enhanced the proliferation of LMP2a-specific CTL. RESULTS: While rIL15 did not change the pattern of cytokines secreted by LMP2a-CTL, rIL12 enhanced the production of Th1/Tc1 cytokines, such as IFN-n, while suppressing the production of the Th2/Tc2 cytokine IL5. DISCUSSION: Stimulation of CTL cultures with rIL12 or rIL15 will generate CTL more rapidly, facilitating the application of this approach for patients with these EBV-associated disorders.

Adenoviridae↗

Does the application of gadolinium-DTPA have an impact on magnetic resonance phase contrast velocity measurements? Results from an in vitro study.

INTRODUCTION/OBJECTIVE: To evaluate the potential influence of various concentrations of gadolinium (Gd)-DTPA on magnetic resonance phase contrast (MR PC) velocimetry. MATERIAL AND METHODS: Imaging was done with a 1.0 T scanner using a standard Flash 2D sequence and a circular polarized extremity coil. In a validated flow phantom with a defined 75% area stenosis different concentrations of Gd-DTPA, diluted in a 10:1 water-yogurt mixture, MR PC measurements were correlated with a Doppler guide wire as gold standard. RESULTS: MR PC measurements correlated well with the Doppler derived data (r=0.99; P<0.01; maximum pre-stenotic velocity: 21.6+/-0.5 cm/s; maximum intra-stenotic velocity: 81.7+/-0.6 cm/s). Following Gd-DTPA administration no significant (P>0.05; Student's t-test) flow measurement changes were noted (maximum pre-stenotic velocity: 21.3+/-1.3 cm/s; maximum intra-stenotic velocity: 84.0+/-3.6 cm/s). However, delineation of the perfused lumen was enhanced after the application of Gd-DTPA. DISCUSSIONS AND CONCLUSION: The application of Gd-DTPA does not affect MR PC velocimetry. However, the application of contrast media allowed a more accurate vessel segmentation. MR PC measurements can be reliably carried out after application of Gd-DTPA.

Blood Flow Velocity↗

Lentiviral transduction of human T-lymphocytes with a RANTES intrakine inhibits human immunodeficiency virus type 1 infection.

Intrakines, modified intracellular chemokines, offer a novel strategy to prevent cellular entry of HIV-1 by blocking the surface expression of HIV-1 co-receptors. To investigate potential clinical applications of the RANTES-intrakine, we explored the use of HIV-1-based lentiviral vectors for therapeutic gene transfer into T-lymphocytes. RANTES-intrakine genes can be efficiently transduced into primary human T-lymphocytes by lentiviral vectors, especially when human T-lymphocytes were stimulated with CD3 and CD28 antibodies. The transduced T cells showed decreased surface expression of the chemokine receptor CCR-5, as well as CCR-1 and CCR-3. This lentivirus-mediated approach to intrakine gene transfer protected human T-lymphocytes from infection by a variety of R5-tropic HIV-1 strains. A quantitative real-time PCR assay, developed to monitor cells for HIV entry and persistence, revealed persistent low copy numbers of proviral HIV DNA in RANTES intrakine-transduced T-lymphocytes during 3-week culture, suggesting that viruses produced from infected untransduced cell populations were unable to infect the surrounding transduced T-lymphocytes. We conclude that targeting HIV-1 co-receptors to block virus entry with lentiviral vectors is an attractive approach to the control of HIV-1 infection.

CD3 Complex↗

[Secretin-stimulated MR cholangiopancreatography (MRCP): visualization of the normal pancreatic duct in comparison with ERCP].

PURPOSE: To determine whether the application of secretin improves the depiction of the normal pancreatic duct and to document the time course of any possible improved visualisation. PATIENTS AND METHODS: Twenty-eight patients with a normal pancreatic ductal system, proved by ERCP, were prospectively enrolled in our study. MRCP was carried out in a 1.0 Tesla unit using a thick slab single-shot turbo-echo sequence (TR: infinity, TE: 1100 ms, FA: 150 degrees, slab thickness: 65 mm). Following acquisition of a non-enhanced image, 1 clinical unit/kg bodyweight of secretin was injected intravenously. During the subsequent ten minutes the MR measurement was repeated every 30 seconds. The images were independently evaluated by two investigators. RESULTS: The improvement in quality after administration of secretin was statistically significant for both investigators (p < 0.05), but no significant difference was found between both investigators concerning the quality of the images (p = 0.49). Prior to the secretin application, the entire ductal system only be evaluated in ten cases (35.7 %) by both investigators, afterwards in 26 cases (92.9 %). Improvement was achieved after a mean time of 1.5 minutes and lasted until the ninth minute. CONCLUSION: Intravenous application of secretin improves image quality of MRCP also in patients with no pancreatic pathology. Improvement begins after 1.5 minutes and lasts for about seven minutes.

Adult↗