Search

This study was undertaken to describe the clinical and imaging characteristics of patients with chorea associated with nonketotic hyperglycemia (C-NKH) in comparison with patients with chorea associated with uremia (C-URE). We retrospectively analyzed the clinical data of consecutive 10 C-NKH and five C-URE patients who were treated between January 1, 2001 and January 31, 2013. Women were more frequently affected by C-NKH (70% vs. 30%) and C-URE (80% vs. 20%) compared with men. The C-NKH patients demonstrated T1-hyperintense and inhomogeneous lesions in the basal ganglia, whereas C-URE patients demonstrated T2-hyperintense and homogeneous lesions in the basal ganglia. The mean time for chorea resolution after treatment was significantly shorter in C-NKH patients than in C-URE patients (4.4 ± 2.6 d vs. 73.8 ± 14.2 d, respectively; P = 0.005). The clinical and imaging features are remarkably different between C-NKH and C-URE patients, suggesting distinct pathogenic mechanisms. © 2015 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Conductive porous materials having a high surface reactivity offer great promise for a broad range of applications. However, a general and scalable synthesis of such materials remains challenging. In this work, the facile synthesis of catalytic metal nanoparticles (NPs) embedded in 2D metal–organic frameworks (MOFs) is reported as highly active and conductive porous materials. After the assembly of 2D conductive MOFs (C‐MOFs), i.e., Cu3(hexahydroxytriphenylene)2 [Cu3(HHTP)2], Pd or Pt NPs are functionalized within the cavities of C‐MOFs by infiltration of metal ions and subsequent reduction. The unique structure of Cu3(HHTP)2 with a cavity size of 2 nm confines the bulk growth of metal NPs, resulting in ultra‐small (≈2 nm) and well‐dispersed metal NPs loaded in 2D C‐MOFs. The Pd or Pt NPs‐loaded Cu3(HHTP)2 exhibits remarkably improved NO2 sensing performance at room temperature due to the high reactivity of catalytic metal NPs and the high porosity of C‐MOFs. The catalytic effect of Pd and Pt NPs on NO2 sensing of Cu3(HHTP)2, in terms of reaction rate kinetics and activation energy, is demonstrated. [ABSTRACT FROM AUTHOR]

1D metal-oxide nanotube (NT) structures have attracted considerable attention for applications in chemical sensors due to their high surface area and unique chemical and physical properties. Moreover, bimodal pores, i.e., meso- and macro-sized pores, which are formed on the shell of NTs, can further facilitate gas penetration into the sensing layers, leading to much improved sensing properties. However, thin-walled NTs with bimodal pore distribution have been rarely fabricated due to the limitations of synthetic methods. Here, Ostwald ripening-driven electrospinning combined with sacrificial templating route using polystyrene (PS) colloid and bioinspired protein is firstly proposed for producing both bi-modal pores and catalyst-loaded thin-walled SnO2 NTs. Homogeneous catalyst loading on porous SnO2 NTs is achieved by the protein cage that contains catalysts and PS colloids and protein shells are thermally decomposed during calcination of electrospun fibers, resulting in the creation of dual-sized pores on NTs. Pt catalyst decorated porous SnO2 NTs (Pt-PS_SnO2 NTs) show exceptionally high acetone gas response, superior selectivity against other interfering gases, and very low limit of detection (10 ppb) to simulated diabetic acetone molecules. More importantly, sensor arrays assembled with developed porous SnO2 NTs enable the direct distinction between the simulated diabetic breath and normal breath from healthy people. [ABSTRACT FROM AUTHOR]

Abstract: Background: Pig islet xenotransplantation is a promising alternative to allogeneic transplantation. However, the wide immunologic barrier between pigs and primates limits the long‐term survival of the graft. MD‐3, a novel monoclonal antibody (mAb) that recognizes a particular epitope of human ICAM‐1, can render T cells tolerant to a xenograft by arresting dendritic cell maturation. We report the long‐term survival of adult wild‐type pig islets and successful retransplantation in nonhuman primates using a protocol comprising induction with MD‐3 mAb and maintenance with anti‐CD154 mAb and sirolimus. Methods: Eleven rhesus monkeys were assigned to three groups. Group 1 (n = 4) involved treatment with MD‐3 induction, short‐term (<4 months) administration of anti‐CD154 mAb, and maintenance therapy with sirolimus. Group 2 (n = 4) involved treatment with MD‐3 induction and long‐term maintenance therapy with anti‐CD154 mAb and sirolimus. Group 3 (n = 3) involved only maintenance therapy with anti‐CD154 mAb and sirolimus. Diabetes was induced in monkeys by streptozotocin, and pig islets (61 000‐112 000 IEQ/kg for each transplant; up to 280 000 IEQ/kg per recipient) were infused through the portal vein. The in vivo functional potency of the isolated islets was tested by minimal model transplant in streptozotocin‐induced diabetic NOD/SCID mice, and the mean AUC of blood glucose level divided by the number of follow‐up days was calculated. Results: The islet grafts survived more than 6 months (between 225 and 727 days) in nine of 12 transplants of MD‐3‐treated groups 1 and 2, whereas in the absence of MD‐3 mAb, survival was <40 days. In three transplants of the MD‐3‐treated Group 2, functional graft survival was only for 104, 125, and 154 days. In these cases, a retrospective analysis suggested that the relatively short survival duration was associated with the relatively high AUC value in the NOD/SCID bioassay. Notably, when retransplantation was performed in Group 3, blood glucose control was extended up to 956 days, which was supported by MD‐3 mAb‐based suppression of adaptive immunity. No replication of cytomegalovirus genes was observed. Conclusions: Long‐term survival of pig islet xenografts and successful retransplantation were achieved with MD‐3 mAb‐based immunosuppression regimen in this pig‐to‐monkey transplantation model. It should be emphasized that these encouraging results were achieved following the transplantation of islets from pigs that had not been genetically modified. Considering that it is possible to further substantially reduce the destruction of grafted islet using genetically modified pig islet, the islet requirement could be reduced and much longer graft survival can be achieved. [ABSTRACT FROM AUTHOR]

Abstract: Background: Islet transplantation is an effective therapy for selected patients with type 1 diabetes with labile glycemic control and hypoglycemic unawareness, but donor organs are limited. Islet xenotransplantation using porcine islets will potentially solve this problem. Although successful proof of concept studies using clinically inapplicable anti‐CD154 monoclonal antibody (mAb) in pig‐to‐non‐human primate (NHP) islet xenotransplantation has been demonstrated by several groups worldwide, potentially clinically applicable anti‐CD40 (2C10R4) mAb‐based studies have not been reported. Methods: Nine streptozotocin (STZ)‐induced diabetic rhesus monkeys were transplanted with adult porcine islets isolated from designated pathogen‐free (DPF) miniature pigs. They were treated with anti‐CD40 mAb‐based immunosuppressive regimen and were divided into 3 groups: anti‐CD40 only group (n = 2), belatacept group (anti‐CD40 mAb+belatacept, n = 2), and tacrolimus group (anti‐CD40 mAb+tacrolimus, n = 5). All monkeys received anti‐thymocyte globulin (ATG), cobra venom factor (CVF), adalimumab, and sirolimus. Blood glucose levels (BGL) and serum porcine C‐peptide concentrations were measured. Humoral and cellular immune responses were assessed by ELISA and ELISPOT, respectively. Liver biopsy and subsequent immunohistochemistry were conducted. Results: All animals restored normoglycemia immediately after porcine islet transplantation and finished the follow‐up without any severe adverse effects except for one animal (R092). Most animals maintained their body weight. Median survival, as defined by a serum porcine C‐peptide concentration of >0.15 ng/mL, was 31, 27, and 60 days for anti‐CD40 only, belatacept, and tacrolimus groups, respectively. Anti‐αGal IgG levels in serum and the number of interferon‐γ secreting T cells in peripheral blood mononuclear cells did not increase in most animals. Conclusion: These results showed that anti‐CD40 mAb combined with tacrolimus was effective in prolonging porcine islet graft survival, but anti‐CD40 mAb was not as effective as anti‐CD154 mAb in terms of preventing early islet loss. [ABSTRACT FROM AUTHOR]

Chemical sensors have been essential components in recent years due to the gathering attention in environmental monitoring and healthcare. In this review, the authors comprehensively highlight recent progresses on the 1D chemiresistive-type sensors based on semiconductor metal oxides (SMOs) and optical-type sensors, which are prepared by electrospinning technique. In the part of chemiresistive-type sensors, diverse synthesis techniques for 1D SMO nanofibrous structure are presented with controlled microstructure and surface morphology. In addition, unique functionalization routes of emerging nanocatalysts encapsulated by bio-inspired templates are described for the next generation catalyst on the 1D SMO nanofibers (NFs). For the optical-type sensors, new classes of 1D NFs employing specific absorption and emission properties are introduced. In particular, diverse 1D NF-based colorimetric and fluorescence sensors as well as Raman and surface-enhanced Raman scattering sensors are covered in the view point of material preparation and optical sensing properties. Finally, the authors prospect future research directions to overcome current limitations and challenges to achieve high performance chemical sensors. [ABSTRACT FROM AUTHOR]

Background and Purpose: Quantitative measurements, as well as qualitative characterizations, of the vessel walls of the small intracranial arteries became clinically available and reliable beyond the resolution limit of 1.5 T high-resolution magnetic resonance imaging (HR-MRI) with the development of 3 T HR-MRI. We present the quantitative dissection findings of spontaneous and unruptured acute intracranial artery dissection (SID) using 3 T HR-MRI and investigate the differences between each cerebral artery.Methods: Twenty-eight lesions (anterior cerebral artery = 6; middle cerebral artery = 4; vertebral artery = 18) from 26 patients (17 male and 9 female patients; mean age = 47 years; age range = 32-74 years) with presumptive diagnoses of SID were included. The diagnosis was determined based on the clinical features, findings on luminal angiography (such as digital subtraction angiography, computed tomography, or magnetic resonance angiography), and HR-MRI. HR-MRI was performed within one month from onset. The neuroimaging indices (maximal outer diameter and area, remodeling index and modified remodeling index, and wall thickness and wall area index) of aneurysmal dilatation and the signal intensities of the intramural hematomas were rated using HR-MRI. The results were compared between each cerebral artery.Results: The maximal outer diameter and area, remodeling index and modified remodeling index, and wall thickness index and length were significantly different between anterior and posterior circulation (P < .05). The mean relative signal intensities of the intramural hematoma showed consistent values, regardless of the cerebral arteries, without significant difference.Conclusions: Neuroimaging indices of aneurysmal dilatation may be adjunctive indicators in the evaluation of SID. [ABSTRACT FROM AUTHOR]

Background Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non-human primates ( NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting. Methods Two diabetic rhesus monkeys were transplanted with porcine islets from wild-type adult Seoul National University ( SNU) miniature pigs with immunosuppression by anti-thymoglobulin ( ATG), cobra venom factor, anti- CD154 monoclonal antibody ( mAb), and sirolimus. CD4+ CD25high CD127low autologous regulatory T cells from the recipients were isolated, ex vivo expanded, and infused at the peri-transplantation period. Blood glucose and porcine C-peptide from the recipients were measured up to 1000 days. Maintenance immunosuppressants including a CD40- CD154 blockade were deliberately discontinued to confirm whether transplantation tolerance was induced by adoptively transferred Tregs. Results After pig islet transplantation via portal vein, blood glucose levels of diabetic recipients became normalized and maintained over 6 months while in immunosuppressive maintenance with a CD40- CD154 blockade and sirolimus. However, the engrafted pig islets in the long-term period were fully rejected by activated immune cells, particularly T cells, when immunosuppressants were stopped, showing a failure of transplantation tolerance induction by autologous Tregs. Conclusions Taken together, autologous Tregs infused at the peri-transplantation period failed to induce transplantation tolerance in pig-to- NHP islet xenotransplantation setting. [ABSTRACT FROM AUTHOR]

Background To understand humoral responses elicited after xenotransplantation, we compared the induction of anti-non-Gal antibodies vs. anti-Gal antibodies in non-human primates ( NHPs) after intraportal porcine islet transplantation ( PITX). Methods Anti-Gal and anti-non-Gal IgGs were analyzed in serial plasma samples of NHP recipients after PITX by enzyme-linked immunosorbent assay ( ELISA) using synthetic Gal and by flow cytometry using α-1,3-galactosyltransferase gene knockout ( GTKO) porcine endothelial cells, respectively. Anti-non-Gal IgG was detected in some recipients after PITX. The specificity of anti-non-Gal IgG was investigated by two-dimensional electrophoresis of the protein extract from GTKO porcine endothelial cells, Western blot analysis of recipient pre- and post- PITX plasma, and MALDI- TOF/ TOF mass spectrometry, revealing albumin, a non-glycosylated protein in the serum supplement of the islets solution, as a putative antigen for anti-non-Gal IgG. The binding of IgG antibodies to human albumin ( HA), bovine albumin ( BA), porcine albumin ( PA), and Gal was compared by ELISA in pre- and post- PITX plasma samples of 30 NHP recipients subjected to intraportal PITX, which were grouped according to the use of CD40- CD154 blockade and sirolimus. Results One of the immunoblot-matched spots was identified as BA by mass spectrometry. By ELISA, the plasma used in the immunoblot analysis revealed strong IgG binding to BA and PA, but not to HA. Anti- PA, anti- BA, and anti-Gal antibodies in NHP recipients 1 month after PITX were detected in 5 (100%), 3 (60%), and 5 (100%), respectively, of the 5 recipients receiving various immunosuppression ( IS) without CD40- CD154 blockade (group I) and in 0 (0%), 0 (0%), and 4 (16%), respectively, of the 25 recipients receiving IS with CD40- CD154 blockade and sirolimus (group II). This finding revealed significant differences between the groups (P < 0.0001, P = 0.0011 and P = 0.0013, respectively). Interestingly, among 15 recipients achieving graft survival longer than 1 month in group II, anti- PA IgG was detected in only 1 recipient (6.7%) 180 days after PITX. However, an increase in anti-Gal IgG was detected in 7 recipients (46.7%) despite maintenance IS with anti- CD154 and sirolimus. This result indicates that anti-Gal IgG is more frequently induced than anti- PA IgG (P = 0.0352). Moreover, induction IS with anti- CD154 and sirolimus suppressed anti-Gal IgG, but not anti- PA and anti- BA IgG, responses in sensitized recipients given a repeat transplantation. Conclusions In NHP recipients of PITX, anti- PA and anti- BA IgG antibodies are elicited by porcine serum included as a supplement in porcine islet preparation. IS including CD40- CD154 blockade and sirolimus suppresses these antibody responses in naïve recipients, but not in sensitized recipients. The elicitation of anti-xenogenic albumin antibodies, a humoral response to a model protein antigen, is distinct from that of anti-Gal antibodies, a response to carbohydrate antigen. [ABSTRACT FROM AUTHOR]

To develop an international consensus regarding the appropriate conditions for undertaking clinical trials in xenocorneal transplantation, here we review specific ethical, logistical, scientific, and regulatory issues regarding xenocorneal transplantation, and propose guidelines for conduct of clinical xenocorneal transplantation trials. These proposed guidelines are modeled on the published consensus statement of the International Xenotransplantation Association regarding recommended guidelines for conduct of clinical islet xenotransplantation. It is expected that this initial consensus statement will be revised over time in response to scientific advances in the field, and changes in the regulatory framework based on accumulating clinical experience. [ABSTRACT FROM AUTHOR]

Front Cover: The feature describes two different types of chemical sensors, i.e., chemiresistive type sensors and optical sensors. For the chemiresistive type sensors, electrical signals are modulated during the reaction with chemical gas species. On the other hand, distinctive color changes are occurred in the case of optical sensors after the reaction with chemical analytes. The feature is designed for the review paper about one‐dimensional nanofibrous sensing structures for chemiresistive type sensors and optical sensors. This is reported by Seon‐Jin Choi, Luana Persano, Andrea Camposeo, Ji‐Soo Jang, Won‐Tae Koo, Sang‐Joon Kim, Hee‐Jin Cho, Il‐Doo Kim and Dario Pisignano, in article number 1600569. [ABSTRACT FROM AUTHOR]