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  • 1
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 24, No. 9 ( 2004-09), p. 1015-1024
    Abstract: A new β-microprobe (βP) has been used to locally measure the time–concentration curve of a radiolabeled substance. The βP, analogous to positron emission tomography methodology, is useful for in vivo animal studies because it can acquire time–concentration curves with high temporal and spatial resolution. Using [ 18 F]fluoro-2-deoxy-d-glucose and βP, we evaluated the reliability of th e biologic parameters and we compared this method with the [ 14 C]2-deoxy-d-glucose autoradiography. βP time–concentration curves in three regions of the brain were obtained from 24 rats. Four kinetic parameters (K 1 -k 4 ) were estimated from 60-minute experimental periods using a three-compartment model. Best fits were obtained when the vascular fraction (F v ) was estimated simultaneously with the four kinetic parameters (K 1 -k 4 ). The mean estimated F v values were about 5.5% for the frontal cortex regions and 8.0% for the cerebellum. Correlation coefficients higher than 0.830 were observed between regional cerebral metabolic rates for glucose (rCMRglc) values obtained by βP and autoradiography. In addition, the βP-derived input function was similar to that obtained by manual sampling. Our findings show that reliable rCMRglc values can be obtained using βP.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2004
    detail.hit.zdb_id: 2039456-1
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  • 2
    In: Cell Transplantation, SAGE Publications, Vol. 15, No. 7 ( 2006-08), p. 621-636
    Abstract: Early revascularization of pancreatic islet cells after transplantation is crucial for engraftment, and it has been suggested that vascular endothelial growth factor-A (VEGF-A) plays a significant role in this process. Although VEGF gene therapy can improve angiogenesis, uncontrolled VEGF secretion can lead to vascular tumor formation. Here we have explored the role of temporal VEGF expression, controlled by a tetracycline (TC)-regulated promoter, on revascularization and engraftment of genetically modified beta cells following transplantation. To this end, we modified the CDM3D beta cell line using a lentiviral vector to promote secretion of VEGF-A either in a TC-regulated (TET cells) or a constitutive (PGK cells) manner. VEGF secretion, angiogenesis, cell proliferation, and stimulated insulin secretion were assessed in vitro. VEGF secretion was increased in TET and PGK cells, and VEGF delivery resulted in angiogenesis, whereas addition of TC inhibited these processes. Insulin secretion by the three cell types was similar. We used a syngeneic mouse model of transplantation to assess the effects of this controlled VEGF expression in vivo. Time to normoglycemia, intraperitoneal glucose tolerance test, graft vascular density, and cellular mass were evaluated. Increased expression of VEGF resulted in significantly better revascularization and engraftment after transplantation when compared to control cells. In vivo, there was a significant increase in vascular density in grafted TET and PGK cells versus control cells. Moreover, the time for diabetic mice to return to normoglycemia and the stimulated plasma glucose clearance were also significantly accelerated in mice transplanted with TET and PGK cells when compared to control cells. VEGF was only needed during the first 2–3 weeks after transplantation; when removed, normoglycemia and graft vascularization were maintained. TC-treated mice grafted with TC-treated cells failed to restore normoglycemia. This approach allowed us to switch off VEGF secretion when the desired effects had been achieved. TC-regulated temporal expression of VEGF using a gene therapy approach presents a novel way to improve early revascularization and engraftment after islet cell transplantation.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2006
    detail.hit.zdb_id: 2020466-8
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  • 3
    In: Molecular Imaging, SAGE Publications, Vol. 14, No. 9 ( 2015-09), p. 7290.2015.00020-
    Type of Medium: Online Resource
    ISSN: 1536-0121 , 1536-0121
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2069848-3
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  • 4
    In: Surgical Innovation, SAGE Publications, Vol. 20, No. 2 ( 2013-04), p. 158-163
    Abstract: The increased distance between surgeon and surgical field is a significant problem in laparoscopic surgery. Robotic surgery, although providing advantages for the operator, increases this gap by completely removing force feedback. Enhancement with visual tools can therefore be beneficial. The goal of this preliminary work was to create a custom plugin for OsiriX to display volume-rendered images in the da Vinci surgeon’s console. The TilePro multi-input display made the generated stereoscopic pairs appear to have depth. Tumor position, vascular supply, spatial location, and relationship between organs appear directly within the surgeon’s field of view. This study presents a case of totally robotic right colectomy for cancer using this new technology. Sight diversion was no longer necessary. Depth perception was subjectively perceived as profitable. Total immersion in the operative field helped compensate for the lack of tactile feedback specific to robotic intervention. This innovative tool is a step forward toward augmented-reality robot-assisted surgery.
    Type of Medium: Online Resource
    ISSN: 1553-3506 , 1553-3514
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
    detail.hit.zdb_id: 2233576-6
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  • 5
    In: Cell Transplantation, SAGE Publications, Vol. 18, No. 1 ( 2009-01), p. 101-110
    Abstract: The aim of this study was to establish hepatocyte isolation in pigs, and to evaluate function of isolated hepatocytes after encapsulation, cryopreservation, and transplantation (Tx) in a mouse model of fulminant liver failure (FLF). After isolation, porcine hepatocytes were microencapsulated with alginate-poly-L-Lysine-alginate membranes and cryopreserved. In vitro, albumin production of free and encapsulated hepatocytes were measured by enzyme linked-immunoadsorbent assay. In vivo, encapsulated hepatocytes were transplanted into different groups of mice with FLF and the following experimental groups were performed: group 1, Tx of empty capsules; group 2, Tx of free primary porcine hepatocytes; group 3, Tx of fresh encapsulated porcine hepatocytes; group 4, Tx of cryopreserved encapsulated porcine hepatocytes. In vitro, fresh or cryopreserved encapsulated porcine hepatocytes showed a continuous decreasing metabolic function over 1 week (albumin and urea synthesis, drug catabolism). In vivo, groups 1 and 2 showed similar survival (18% and 25%, respectively, p 〉 0.05). In groups 3 and 4, Tx of fresh or cryopreserved encapsulated porcine hepatocytes significantly increased survival rate to 75% and 68%, respectively ( p 〈 0.05). Primary porcine hepatocytes maintained metabolic functions after encapsulation and cryopreservation. In mice with FLF, Tx of encapsulated xenogeneic hepatocytes significantly improved survival. These results indicate that porcine hepatocytes can successfully be isolated, encapsulated, stored using cryopreservation, and transplanted into xenogeneic recipients with liver failure and sustain liver metabolic functions.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
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  • 6
    In: Cell Transplantation, SAGE Publications, Vol. 21, No. 11 ( 2012-11), p. 2339-2350
    Abstract: The aim of the present study was to assess the efficiency of cell-based immune assays in the detection of alloreactivity after islet transplantation and to correlate these results with clinical outcome. Mixed lymphocyte cultures were performed with peripheral blood mononuclear cells from recipients ( n = 14), donors, or third party. The immune reactivity was assessed by the release of IFN-γ (ELISpot), cell proliferation (FACS analysis for Ki67), and cytokine quantification (Bioplex). Islet function correlated with the number of IFN-γ-secreting cells following incubation with donor cells ( p = 0.007, r = –0.50), but not with third party cells ( p = 0.61). Similarly, a high number of donor-specific proliferating cells was associated with a low islet function ( p = 0.006, r = −0.51). Proliferating cells were mainly CD3 + CD4 + lymphocytes and CD3 - CD56 + natural killer cells (with low levels of CD3 + CD8 + lymphocytes). Patients with low islet function had increased levels of CD4 + Ki67 + cells ( p ≤ 0.0001), while no difference was observed in CD8 + Ki67 + and CD56 + Ki67 + cells. IFN-γ, IL-5, and IL-17 levels were increased in patients with low islet function, but IL-10 levels tended to be lower. IFN-γ-ELISpot, proliferation, and cytokines were similarly accurate in predicting clinical outcome (AUC = 0.77 ± 0.088, 0.85 ± 0.084, and 0.88 ± 0.074, respectively). Cellular immune reactivity against donor cells correlates with posttransplant islet function. The tested assays have the potential to be of substantial help in the management of islet graft recipients and deserve prospective validation.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
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  • 7
    In: Cell Transplantation, SAGE Publications, Vol. 25, No. 12 ( 2016-12), p. 2259-2268
    Abstract: Islet transplantation is an effective treatment for selected patients with type 1 diabetes. However, an accurate test still lacks for the early detection of graft rejection. Blood samples were prospectively collected in four university centers (Geneva, Grenoble, Montpellier, and Strasbourg). Peripheral blood mononuclear cells were stimulated with donor splenocytes in the presence of interleukin-2. After 24 h of incubation, interferon-γ (IFN-γ) ELISpot analysis was performed. After a total of 5 days of incubation, cell proliferation was assessed by fluorescence-activated cell sorting (FACS) analysis for Ki-67. Immunological events were correlated with adverse metabolic events determined by loss of ≥1 point of β-score and/or an increased insulin intake ≥10%. Twenty-five patients were analyzed; 14 were recipients of islets alone, and 11 combined with kidney. Overall, 76% (19/25) reached insulin independence at one point during a mean follow-up of 30.7 months. IFN-γ ELISpot showed no detectable correlation with adverse metabolic events [area under the curve (AUC) = 0.57]. Similarly, cell proliferation analysis showed no detectable correlation with adverse metabolic events (CD3 + / CD4 + AUC = 0.54; CD3 + /CD8 + AUC = 0.55; CD3-/CD56 + AUC = 0.50). CD3-/CD56 + cell proliferation was significantly higher in patients with combined kidney transplantation versus islet alone (6 months, p = 0.010; 12 months, p = 0.016; and 24 months, p = 0.018). Donor antigen-stimulated IFN-γ production and cell proliferation do not predict adverse metabolic events after islet transplantation. This suggests that the volume of transplanted islets is too small to produce a detectable systemic immune response and/or that alloimmune rejection is not the sole reason for the loss of islet graft function.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
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  • 8
    In: Cell Transplantation, SAGE Publications, Vol. 19, No. 12 ( 2010-12), p. 1573-1585
    Abstract: Ex vivo labeling of islets with superparamagnetic iron oxide (SPIO) nanoparticles allows posttransplant MRI imaging of the graft. In the present study, we compare two clinical grade SPIOs (ferucarbotran and ferumoxide) in terms of toxicity, islet cellular uptake, and MRI imaging. Human islets (80–90% purity) were incubated for 24 h with various concentrations of SPIOs (14–280 μg/ml of iron). Static incubations were performed, comparing insulin response to basal (2.8 mM) or high glucose stimulation (16.7 mM), with or without cAMP stimulation. Insulin and Perl's (assessment of iron content) staining were performed. Electronic microscopy analysis was performed. Labeled islets were used for in vitro or in vivo imaging in MRI 1.5T. Liver section after organ removal was performed in the same plane as MRI imaging to get a correlation between histology and radiology. Postlabeling islet viability (80 ± 10%) and function (in vitro static incubation and in vivo engraftment of human islets in nude mice) were similar in both groups. Iron uptake assessed by electron microscopy showed iron inclusions within the islets with ferucarbotran, but not with ferumoxide. MRI imaging (1.5T) of phantoms and of human islets transplanted in rats, demonstrated a strong signal with ferucarbotran, but only a weak signal with ferumoxide. Signal persisted for 〉 8 weeks in the absence of rejection. An excellent correlation was observed between radiologic images and histology. The hepatic clearance of intraportally injected ferucarbotran was faster than that of ferumoxide, generating less background. A rapid signal decrease was observed in rejecting xenogeneic islets. According to the present data, ferucarbotran is the most appropriate of available clinical grade SPIOs for human islet imaging.
    Type of Medium: Online Resource
    ISSN: 0963-6897 , 1555-3892
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 9
    In: The Neuroradiology Journal, SAGE Publications, Vol. 30, No. 5 ( 2017-10), p. 429-436
    Abstract: The aim of this preliminary study is to evaluate the results of T1-weighted dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in pediatric patients at 1.5T, with a low peripheral intravenous gadoteric acid injection rate of 1 ml/s. Materials and methods Children with neurological symptoms were examined prospectively with conventional MRI and T1-weighted DCE MRI. An magnetic resonance perfusion analysis method was used to obtain time–concentration curves (persistent pattern, type-I; plateau pattern, type-II; washout pattern, type-III) and to calculate pharmacokinetic parameters. A total of two radiologists manually defined regions of interest (ROIs) in the part of the lesion exhibiting the greatest contrast enhancement and in the surrounding normal or contralateral tissue. Lesion/surrounding tissue or contralateral tissue pharmacokinetic parameter ratios were calculated. Tumors were categorized by grade (I–IV) using the World Health Organization (WHO) Grade. Mann–Whitney testing and receiver-operating characteristic (ROC) curves were performed. Results A total of nine boys and nine girls (mean age 10.5 years) were included. Lesions consisted of 10 brain tumors, 3 inflammatory lesions, 3 arteriovenous malformations and 2 strokes. We obtained analyzable concentration–time curves for all patients (6 type-I, 9 type-II, 3 type-III). K trans between tumor tissue and surrounding or contralateral tissue was significantly different ( p = 0.034). K trans ratios were significantly different between grade I tumors and grade IV tumors ( p = 0.027) and a K trans ratio value superior to 0.63 appeared to be discriminant to determine a grade IV of malignancy. Conclusions Our results confirm the feasibility of pediatric T1-weighted DCE MRI at 1.5T with a low injection rate, which could be of great value in differentiating brain tumor grades.
    Type of Medium: Online Resource
    ISSN: 1971-4009 , 2385-1996
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2622347-8
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  • 10
    In: Cardiovascular Surgery, SAGE Publications, Vol. 10, No. 1 ( 2002-02), p. 19-22
    Abstract: The development of severe aorto-ilio-femoral atherosclerotic disease in a patient with a previous double transplantation, kidney and pancreas, is a major surgical challenge. The transplanted organs have to be protected from extensive ischemia during the vascular reconstructive procedure and achieve optimal revascularization. The surgical management of a complex case where regional extra-corporeal circulation was used to protect transplanted pancreas and kidney during aorto-bifemoral vascular grafting in a 39 yr old diabetic patient is described. Regional femoro-femoral extra-corporeal circulation with an oxygenator is a safe technique that allows time for the proximal revascularization, minimizes the warm organ ischemia time and results in preservation of organ function.
    Type of Medium: Online Resource
    ISSN: 0967-2109
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2002
    detail.hit.zdb_id: 2143006-8
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