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101.
102.
Kállay K Liptai Z Benyó G Kassa C Goda V Sinkó J Tóth A Kriván G 《Metabolic brain disease》2012,27(2):193-196
Lesch-Nyhan syndrome (LNS) is a chronic, progressive neurodevelopmental disorder causing motor and behavioral dysfunction
due to decreased synthesis of the enzyme hypoxantine-guanine phosphoribosyltransferase (HPRT). Affected boys have mental retardation,
delayed development, extrapyramidal motor disturbances and self-injuring behavior. As hematopoietic stem cell transplantation
(HSCT) has been shown to be effective in several neurodevelopmental inborn errors, we hypothesized that it could be favorable
in LNS as well. Following a myeloablative conditioning regimen (busulphan 3.2 mg/kg/day for 4 days, cyclophosphamide 60 mg/kg/day
for 2 days with ATG Thymoglobin 2.5 mg/kg/day for 4 days) an unrelated umbilical cord blood unit was transfused at the age
of 2 years. The graft was a 6/6 HLA-matched at HLA-A, B loci by antigen level, and at DRB1 by allelic level typing. Infused
total nucleated cell dose was 3.6 × 10e7 per kilogram body weight. Serum HPRT levels reached normal values by the end of the
sixth month post transplant. Slow neurodevelopmental improvement seen during the three-year follow-up and the missing self-injuring
behavior can be considered as a proof for the presence of enzyme-competent cells behind the blood–brain barrier. 相似文献
103.
104.
Andrew J Burghardt Jean‐Baptiste Pialat Galateia J Kazakia Stephanie Boutroy Klaus Engelke Janina M Patsch Alexander Valentinitsch Danmei Liu Eva Szabo Cesar E Bogado Maria Belen Zanchetta Heather A McKay Elizabeth Shane Steven K Boyd Mary L Bouxsein Roland Chapurlat Sundeep Khosla Sharmila Majumdar 《Journal of bone and mineral research》2013,28(3):524-536
High‐resolution peripheral quantitative computed tomography (HR‐pQCT) has recently been introduced as a clinical research tool for in vivo assessment of bone quality. The utility of this technology to address important skeletal health questions requires translation to standardized multicenter data pools. Our goal was to evaluate the feasibility of pooling data in multicenter HR‐pQCT imaging trials. Reproducibility imaging experiments were performed using structure and composition‐realistic phantoms constructed from cadaveric radii. Single‐center precision was determined by repeat scanning over short‐term (<72 hours), intermediate‐term (3–5 months), and long‐term intervals (28 months). Multicenter precision was determined by imaging the phantoms at nine different HR‐pQCT centers. Least significant change (LSC) and root mean squared coefficient of variation (RMSCV) for each interval and across centers was calculated for bone density, geometry, microstructure, and biomechanical parameters. Single‐center short‐term RMSCVs were <1% for all parameters except cortical thickness (Ct.Th) (1.1%), spatial variability in cortical thickness (Ct.Th.SD) (2.6%), standard deviation of trabecular separation (Tb.Sp.SD) (1.8%), and porosity measures (6% to 8%). Intermediate‐term RMSCVs were generally not statistically different from short‐term values. Long‐term variability was significantly greater for all density measures (0.7% to 2.0%; p < 0.05 versus short‐term) and several structure measures: cortical thickness (Ct.Th) (3.4%; p < 0.01 versus short‐term), cortical porosity (Ct.Po) (15.4%; p < 0.01 versus short‐term), and trabecular thickness (Tb.Th) (2.2%; p < 0.01 versus short‐term). Multicenter RMSCVs were also significantly higher than short‐term values: 2% to 4% for density and micro–finite element analysis (µFE) measures (p < 0.0001), 2.6% to 5.3% for morphometric measures (p < 0.001), whereas Ct.Po was 16.2% (p < 0.001). In the absence of subject motion, multicenter precision errors for HR‐pQCT parameters were generally less than 5%. Phantom‐based multicenter precision was comparable to previously reported in in vivo single‐center precision errors, although this was approximately two to five times worse than ex vivo short‐term precision. The data generated from this study will contribute to the future design and validation of standardized procedures that are broadly translatable to multicenter study designs. © 2013 American Society for Bone and Mineral Research. 相似文献
105.
Miklos Z. Molnar Hirohito Ichii James Lineen Clarence E. Foster rd Zoltan Mathe Jeffrey Schiff S. Joseph Kim Madeleine V. Pahl Alpesh N. Amin Kamyar Kalantar‐Zadeh Csaba P. Kovesdy 《Seminars in dialysis》2013,26(6):667-674
In the last decade, the number of patients starting dialysis after a failed kidney transplant has increased substantially. These patients appear to be different from their transplant‐naïve counterparts, and so may be the timing of dialysis therapy initiation. An increasing number of studies suggest that in transplant‐naïve patients, later dialysis initiation is associated with better outcomes. Very few data are available on timing of dialysis reinitiation in failed transplant recipients, and they suggest that an earlier return to dialysis therapy tended to be associated with worse survival, especially among healthier and younger patients and women. Failed transplant patients may also have unique issues such as continuation of immunosuppression versus withdrawal or the need for remnant allograft nephrectomy with regard to dialysis reinitiation. These patients may have a different predialysis preparation work‐up, worse blood pressure control, higher or lower serum phosphorus levels, lower serum bicarbonate concentration, and worse anemia management. The choice of dialysis modality may also represent an important question for these patients, even though there appears to be no difference in mortality between patients starting peritoneal versus hemodialysis. Finally, failed transplant patients returning to dialysis appear to have a higher mortality rate compared with transplant‐naïve incident dialysis patients, especially in the first several months of dialysis therapy. In this review, we will summarize the available data related to the timing of dialysis initiation and outcomes in failed kidney transplant patients after returning to dialysis. 相似文献
106.
Péter Monostori Gabriella F. Kocsis Zsuzsanna Ökrös Péter Bencsik Orsolya Czétényi Zoltán Kiss Balázs Gellén Csaba Bereczki Imre Ocsovszki Judit Pipis János Pálóczi Márta Sárközy Szilvia Török Ilona S. Varga István Kiss Eszter Fodor Tamás Csont Péter Ferdinandy Sándor Túri 《Clinical and experimental nephrology》2013,17(4):569-574
Background
The development of erythropoiesis-stimulating agents (ESAs) with extended serum half-lives has allowed marked prolongation of the administration intervals. The level of oxidative stress is increased in chronic kidney disease, and is reportedly decreased after long-term ESA treatment. However, the effect of different dosing regimens of ESAs on oxidative stress has not been elucidated.Methods
Five-sixths nephrectomized (NX) rats received either 0.4 μg/kg darbepoetin alfa (DA) weekly or 0.8 μg/kg DA fortnightly between weeks 4 and 10. NX animals receiving saline and a sham-operated (SHAM) group served as controls. The levels of oxidized and reduced glutathione (GSSG, GSH) were followed from blood samples drawn fortnightly.Results
During the follow-up, the ratios GSSG/GSH showed similar trends in both DA groups, levels being significantly lower than those in the SHAM group at weeks 8 and 10. GSSG levels were lower than the baseline throughout the study in all groups except for NX controls. The GSH levels were increased in all three NX groups (weeks 6–10) compared with both the baseline and the SHAM groupConclusion
Our results suggest that the extent of oxidative stress is similar in response to different dosing regimens of DA in 5/6 NX rats when comparable hemoglobin levels are maintained. These findings remain to be confirmed in chronic kidney disease patients. 相似文献107.
Lohinai Z Keremi B Szoko E Tabi T Szabo C Tulassay Z Levine M 《Journal of periodontology》2012,83(8):1048-1056
Background: Dental biofilms contain a protein that inhibits mammalian cell growth, possibly lysine decarboxylase from Eikenella corrodens. This enzyme decarboxylates lysine, an essential amino acid for dentally attached cell turnover in gingival sulci. Lysine depletion may stop this turnover, impairing the barrier to bacterial compounds. The aims of this study are to determine biofilm lysine and cadaverine contents before oral hygiene restriction (OHR) and their association with plaque index (PI) and gingival crevicular fluid (GCF) after OHR for 1 week. Methods: Laser‐induced fluorescence after capillary electrophoresis was used to determine lysine and cadaverine contents in dental biofilm, tongue biofilm, and saliva before OHR and in dental biofilm after OHR. Results: Before OHR, lysine and cadaverine contents of dental biofilm were similar and 10‐fold greater than in saliva or tongue biofilm. After 1 week of OHR, the biofilm content of cadaverine increased and that of lysine decreased, consistent with greater biofilm lysine decarboxylase activity. Regression indicated that PI and GCF exudation were positively related to biofilm lysine after OHR, unless biofilm lysine exceeded the minimal blood plasma content, in which case PI was further increased but GCF exudation was reduced. Conclusions: After OHR, lysine decarboxylase activity seems to determine biofilm lysine content and biofilm accumulation. When biofilm lysine exceeds minimal blood plasma content after OHR, less GCF appeared despite more biofilm. Lysine appears important for biofilm accumulation and the epithelial barrier to bacterial proinflammatory agents. Inhibiting lysine decarboxylase may retard the increased GCF exudation required for microbial development and gingivitis. 相似文献
108.
Zsolt Csaba Eric Krejci Véronique Bernard 《The Journal of comparative neurology》2013,521(9):2008-2024
In many brain areas, few cholinergic synapses are identified. Acetylcholine is released into the extracellular space and acts through diffuse transmission. Motoneurons, however, are contacted by numerous cholinergic terminals, indicating synaptic cholinergic transmission on them. The muscarinic m2 receptor is the major acetylcholine receptor subtype of motoneurons; therefore, we analyzed the localization of the m2 receptor in correlation with synapses by electron microscopic immunohistochemistry in the mouse trigeminal, facial, and hypoglossal motor nuclei. In all nuclei, m2 receptors were localized at the membrane of motoneuronal perikarya and dendrites. The m2 receptors were concentrated at cholinergic synapses located on the perikarya and most proximal dendrites. However, m2 receptors at cholinergic synapses represented only a minority (<10%) of surface m2 receptors. The m2 receptors were also enriched at glutamatergic synapses in both motoneuronal perikarya and dendrites. A relatively large proportion (20–30%) of plasma membrane–associated m2 receptors were located at glutamatergic synapses. In conclusion, the effect of acetylcholine on motoneuron populations might be mediated through a synaptic as well as diffuse type of transmission. J. Comp. Neurol. 521:2008–2024, 2013. © 2012 Wiley Periodicals, Inc. 相似文献
109.
MicroRNA‐21 (miR‐21) expression in hypothermic machine perfusate may be predictive of early outcomes in kidney transplantation 下载免费PDF全文
Usman Khalid Elijah Ablorsu Laszlo Szabo Robert H. Jenkins Timothy Bowen Rafael Chavez Donald J. Fraser 《Clinical transplantation》2016,30(2):99-104
Hypothermic machine perfusion is effective in improving outcome following kidney transplantation. Molecular analyses of hypothermic machine perfusate (HMP) have the potential to identify biomarkers of organ viability prior to transplantation, offering significant advantages to the transplant surgeon, and leading to a potential increase in the organ donor pool. MicroRNAs are emerging as important biomarkers in the context of kidney injury and transplantation. Recent data demonstrate increased microRNA‐21 (miR‐21) expression in the kidney following acute kidney injury. This study investigated the potential of miR‐21 detected in HMP to act as a sentinel for early kidney transplant outcomes. MiR‐21 was found to be readily detectable in HMP by RT‐qPCR. Eleven ECD kidneys were maintained on a hypothermic machine perfusion system for a median 627 (range 117–1027) minutes, and evaluation of flow and resistance characteristics suggested stability on the machine from 60 min post‐perfusion. MiR‐21 quantification at 60 min post‐perfusion correlated with eGFR at 6 and 12 months post‐transplantation. These data suggest that miR‐21 expression in HMP may be predictive of early outcomes following kidney transplantation. In the era of ECD kidneys, a reliable measure of organ quality is urgently needed, and this study suggests miR‐21 may be such a marker. 相似文献
110.
Influence of antithymocyte globulin treatment of brain‐dead organ donor on inflammatory response in cardiac grafts: an experimental study in mice 下载免费PDF全文
Jamila Kremer Gabriela K. Muschitz Klaus Aumayr Philipp Moser Gabor Szabo Alexander Weymann Andreas Zuckermann Bruno K. Podesser 《Transplant international》2016,29(12):1329-1336
The expression of proinflammatory cytokines in donor hearts after antithymocyte globulin (ATG) treatment given prior to organ removal was evaluated to analyze changes in inflammatory response. Adult female OF‐1 mice were randomized into brain death (BD) groups (BD Control, BD ATG) with or without treatment, and Controls (Control, ATG). BD induction was performed through gradual inflation of an intracranial positioned balloon catheter. At the end of a 6‐h observation period, ATG (1 mg/kg BW) was given intravenously. After 45 min, the donor hearts were removed. Proinflammatory markers IL‐2 and IL‐6 were examined using ELISA and immunohistochemistry staining. After single administration of ATG, the inflammatory reaction in the myocardium showed a significant reduction in IL‐2 expression (BD Control vs. BD ATG, P = 0.033). Our investigation showed expected increase in proinflammatory mediators after BD. This increase was abolished by single infusion of ATG, indicated by significant reduction in IL‐2 levels in the myocardium. We observed a reduction of IL‐6 deposition in media cells in ATG‐treated specimens. Further research is necessary to evaluate the role of ATG in donor management considering a potentially positive effect of ATG on IL‐2‐directed inflammatory response and possible reduction of IL‐6‐mediated vascular changes. 相似文献