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van der Meulen Merel Verstegen Marco J. T. Lobatto Daniel J. Kleijwegt Maarten C. Pereira Alberto M. Biermasz Nienke R. van Furth Wouter R. Zamanipoor Najafabadi Amir H. 《Pituitary》2022,25(2):308-320
Pituitary - Endoscopic transsphenoidal surgery causes nasal morbidity and negatively affects health-related quality of life (HRQoL). Knowledge on actionable symptoms that could improve... 相似文献
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Diminished clearance of soluble aggregates of human immunoglobulin G in patients with rheumatoid arthritis 总被引:1,自引:0,他引:1
S Lobatto M R Daha M L Westedt E K Pauwels J H Evers-Schouten A A Voetman A Cats L A van Es 《Scandinavian journal of rheumatology》1989,18(2):89-96
Investigation of the capacity of the mononuclear phagocyte system to remove immune complexes from the circulation was performed by the administration of 125I-labelled aggregates of human immunoglobulin G (AIgG) to patients with seropositive rheumatoid arthritis and healthy volunteers. It was found that the rate at which AIgG disappeared from the circulation was significantly prolonged in patients with RA, t1/2 61 +/- 49 min, versus 26 +/- 8 min in healthy volunteers (p less than 0.01). We were not able to establish a correlation between the t1/2 of AIgG and immune complex levels in the circulation, or between t1/2 and articular disease activity (Ritchie index). The sites of removal of AIgG from the circulation were analysed by determining radioactivity levels detectable over liver, spleen and heart. No correlation was found between t1/2 and liver/spleen uptake ratios. We have demonstrated that the removal of AIgG from the circulation of patients with RA is abnormal, though the biological significance of this finding remains to be determined. 相似文献
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YongTae Kim Mark E. Lobatto Tomohiro Kawahara Bomy Lee Chung Aneta J. Mieszawska Brenda L. Sanchez-Gaytan Francois Fay Max L. Senders Claudia Calcagno Jacob Becraft May Tun Saung Ronald E. Gordon Erik S. G. Stroes Mingming Ma Omid C. Farokhzad Zahi A. Fayad Willem J. M. Mulder Robert Langer 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(3):1078-1083
Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system.Improving the design of nanomedicines is key for their success and ultimate clinical application (1). The accumulation of such therapeutic or diagnostic nanomaterials primarily relies on enhanced endothelial permeability of the microvasculature in diseased tissue (2). This holds true for a wide range of pathological conditions, including inflammation, atherosclerosis, and most notably, oncological disease (3–6). Although attributed to the enhanced permeability and retention (EPR) effect, the exact mechanism by which nanoparticles accumulate in tumors continues to be a topic of research (7, 8). The “leaky” vasculature of tumors, which facilitates the extravasation of nanoparticles from microvessels (9), is a heterogeneous phenomenon that varies between different tumor models and even more so in patients. Moreover, the exploitation of nanomedicines in other conditions with enhanced microvessel permeability has only recently begun to be studied in detail. For example, in the last 5 y, a small but increasing number of preclinical studies that apply nanoparticle therapy in atherosclerosis models has surfaced (10). Although several targeting mechanisms have been proposed (4), the exact mechanism by which nanoparticles accumulate in atherosclerotic plaques remains to be investigated, but is likely facilitated by highly permeable neovessels that penetrate into the plaque from the vasa vasorum (Fig. 1A), a network of microvessels that supplies the wall of larger vessels (11).Open in a separate windowFig. 1.Development of an endothelialized microfluidic device to probe nanoparticle translocation over a permeable microvessel. (A) Schematics of continuous normal capillaries surrounding the vessel wall as well as permeable capillaries that penetrate into the atherosclerotic plaque from the vasa vasorum. (B) Schematic of an endothelialized microfluidic device that consists of two-layer microfluidic channels that are separated by a porous membrane (3 μm pore) on which ECs are grown. (C) TEER was dynamically measured across the endothelial layer on the membrane between the upper and lower channels. (D) A well-established monolayer of the microvascular endothelium is formed at TEER ∼400 (Ω·cm2). (E) The monolayer becomes highly permeable when stimulated with the inflammatory mediator, TNF-α, as well as with shear stress, with disruption of intercellular junctional structures (i.e., adherens junctions) between ECs, as evidenced by patchy expression of VE–cadherin (green) in the image on the right versus the left. Blue depicts nuclei stained with DAPI. (Scale bar, 20 μm.) (F) FITC–albumin translocation through the endothelial monolayer increases when the chip is treated with TNF-α. (G) The chip with endothelium cultured in different culture media [base, +FBS, +growth factors (GFs)] for 6 h shows a decrease in TEER with increased FITC–albumin translocation. No cell indicates the membrane only. TEER was normalized to the level with no cells (membrane only). (H) Schematic and TEM image of PEGylated lipid-coated nanoparticles encapsulating PLGA-conjugated AuNCs and Cy5.5. The average size was 69.7 ± 14 nm, which was measured from TEM images. (Scale bar, 100 nm.) Details on labeling, synthesis, characterization, and large-scale production procedures can be found in Materials and Methods and Fig. S2.Advances in biomedical imaging allow the study of plaque-targeting nanoparticles in a dynamic fashion with exceptional detail (12, 13). Microchip technology has the potential to monitor nanoparticle behavior at the (sub)cellular level. Microfluidic chips in which endothelial cells (ECs) are grown in the channels can serve as unique in vitro test systems to study microvascular function and associated disorders (14–18). They allow the isolation of specific biological hallmarks relevant to nanoparticle accumulation, such as the leaky endothelium. In the current study, we validate the potential utility of our microchip technology to study nanoparticle translocation over the endothelium and combine this with in vivo and ex vivo multimodality imaging studies on a rabbit model to better understand nanoparticle targeting of atherosclerotic plaques. 相似文献
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Paul G.G. Gerlag Sacha Lobatto Willem M.M. Driessen Pius F.L. Deckers Johannes P. Van Hooff Ed Schröder Karel M. Assmann Urbain J.G. Van Haelst 《Journal of hepatology》1985,1(4):339-348
An unusual hepatic disease developed in 3 patients with a well-functioning kidney graft 16-24 months after transplantation. Vague abdominal pain, increased bleeding tendency and edema were initial complaints, and hepato- or splenomegaly and ascites were found as well. Liver function tests were not or only mildly disturbed; hemolysis and pancytopenia were always present. Colloid uptake was absent at liver scintigraphy and the hepatic venous wedge pressure was increased. Esophageal varices were demonstrated. Liver biopsy showed extensive midzonal and pericentral sinusoidal dilatation. After discontinuation of azathioprine the symptoms and the extent of sinusoidal dilatation disappeared gradually, but after 1-3 years fibrosis or micronodular cirrhosis had developed and splenomegaly with hypersplenism remained. These observations strongly suggest an association between chronic use of azathioprine and the development of venous congestion of the liver with sinusoidal dilatation, eventually resulting in chronic liver disease. 相似文献
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Treatment of severe hypothyroidism in a patient with progressive renal failure leads to significant improvement of renal function 总被引:1,自引:0,他引:1
The case of a 41-year-old patient with end-stage renal failure and diabetes mellitus Type 1 who was being prepared for renal replacement therapy is described. After severe hypothyroidism was diagnosed, thyroid hormone substitution therapy was started. Subsequently, a substantial decline in serum creatinine was observed. Creatinine clearance rose from 19 to 40 ml/min and renal replacement therapy was no longer imminent. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown amelioration of end-stage renal failure as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. Diagnosing signs of hypothyroidism and therapy with thyroid hormone in progressive renal failure could be very important in delaying the need for renal replacement therapy. 相似文献
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Mulder WJ Cormode DP Hak S Lobatto ME Silvera S Fayad ZA 《Nature clinical practice. Cardiovascular medicine》2008,5(Z2):S103-S111
Targeted imaging and therapeutics is becoming a field of prime importance in the study and treatment of cardiovascular disease; it promises to enable early diagnosis, promote improved understanding of pathology, and offer a way to improve therapeutic efficacy. Agents, particularly for cardiovascular disease, have been reported to permit the in vivo imaging, by multiple modalities, of macrophages, vascular targets such as vascular cell adhesion molecule 1, and markers for angiogenesis such as alpha(v)beta(3) integrin. In this Article, we first discuss the general concept of multimodality nanoparticles and then focus in greater depth on their clinical application for molecular imaging and therapy. Lastly, several examples of cardiovascular applications are discussed, including combined imaging and therapy approaches. 相似文献
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Cornelie D. Andela Daniel J. Lobatto Alberto M. Pereira Wouter R. van Furth Nienke R. Biermasz 《Pituitary》2018,21(2):208-216
After treatment for a non-functioning pituitary adenoma (NFA) health-related quality of life (HR-QoL) improves considerably. However, the literature about the normalization of HR-QoL after treatment is inconclusive. Some researchers described a persistently decreased HR-QoL compared to reference data, while others did not. Considering this variety in observed HR-QoL outcomes, the aim of the present review was to provide a literature overview of health outcomes in patients with a NFA, using a conceptual HR-QoL model. A concrete conceptualization of the health outcomes of patients with a NFA can be helpful to understand the observed variety in HR-QoL outcomes and to improve clinical care and guidance of these patients. For this conceptualization, the Wilson and Cleary model was used. This model has a biopsychosocial character and has been validated in several patient populations. In the present review, health outcomes of patients with a NFA were described at each stage of the model e.g. biological and physiological variables, symptom status, functional status, general health perceptions and overall HR-QoL. The Wilson–Cleary model elucidates that elements at each stage of the model can contribute to the impairment in HR-QoL of patients with a NFA, which explains the reported variety in the literature. Furthermore, by applying the model, potential interventions targeting these elements can be identified. While optimal biomedical treatment has always been the focus, it is clearly not sufficient for good HR-QoL in patients with a NFA. Further improvement of HR-QoL should be supported by a pituitary specific care trajectory, including psychosocial care (e.g. self-management training), to beneficially affect characteristics of the patient and the (healthcare) environment, with the utmost goal to optimize HR-QoL in patients after treatment. 相似文献
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Daniel J. Lobatto Anath N. V. Steffens Amir H. Zamanipoor Najafabadi Cornelie D. Andela Alberto M. Pereira Wilbert B. van den Hout Wilco C. Peul Thea P. M. Vliet Vlieland Nienke R. Biermasz Wouter R. van Furth 《Pituitary》2018,21(6):593-604