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1.
Nat Mater ; 23(5): 612-618, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38321240

RESUMEN

Many superconducting systems with broken time-reversal and inversion symmetry show a superconducting diode effect, a non-reciprocal phenomenon analogous to semiconducting p-n-junction diodes. While the superconducting diode effect lays the foundation for realizing ultralow dissipative circuits, Josephson-phenomena-based diode effect (JDE) can enable the realization of protected qubits. The superconducting diode effect and JDE reported thus far are at low temperatures (~4 K), limiting their applications. Here we demonstrate JDE persisting up to 77 K using an artificial Josephson junction of twisted layers of Bi2Sr2CaCu2O8+δ. JDE manifests as an asymmetry in the magnitude and distributions of switching currents, attaining the maximum at 45° twist. The asymmetry is induced by and tunable with a very small magnetic field applied perpendicular to the junction and arises due to interaction between Josephson and Abrikosov vortices. We report a large asymmetry of 60% at 20 K. Our results provide a path towards realizing superconducting Josephson circuits at liquid-nitrogen temperature.

2.
Bioconjug Chem ; 34(8): 1398-1406, 2023 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-37534797

RESUMEN

Small molecule fluorescent probes that bind selectively to plant cell wall polysaccharides have been instrumental in elucidating the localization and function of these glycans. Arabinogalactan proteins (AGPs) are cell wall proteoglycans implicated in essential functions such as cell signaling, plant growth, and programmed cell death. There is currently no small molecule probe capable of fluorescently labeling AGPs. The Yariv reagents are the only small molecules that bind AGPs, and have been used to study AGP function and isolate AGPs via precipitation of an AGP-Yariv complex. However, the Yariv reagents are not fluorescent, rendering them ineffective for localization studies using fluorescence microscopy. A fluorescent version of a Yariv reagent that is capable of both binding as well as imaging AGPs would provide a powerful tool for studying AGPs in planta. Herein, we describe the synthesis of an azido analog of the Yariv reagent that can be further functionalized with a fluorophore to provide a glycoconjugate that binds AGPs and is fluorescent. We show that the modified reagent binds gum arabic in in vitro binding assays when used in conjunction with the ßGlcYariv reagent. Fluorescent imaging of AGPs in fixed maize leaf tissue enables localization of AGPs to cell walls in the leaf. Significantly, imaging can also be carried out using fresh tissue. This represents the first small molecule probe that can be used to visualize AGPs using fluorescence microscopy.


Asunto(s)
Glucósidos , Floroglucinol , Glucósidos/metabolismo , Floroglucinol/metabolismo , Membrana Celular/metabolismo , Microscopía Fluorescente
3.
Microbiology (Reading) ; 168(4)2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35467499

RESUMEN

Despite renewed interest, development of chemical biology methods to study peptidoglycan metabolism has lagged in comparison to the glycobiology field in general. To address this, a panel of diamides were screened against the Gram-positive bacterium Streptococcus pneumoniae to identify inhibitors of bacterial growth. The screen identified the diamide masarimycin as a bacteriostatic inhibitor of S. pneumoniae growth with an MIC of 8 µM. The diamide inhibited detergent-induced autolysis in a concentration-dependent manner, indicating perturbation of peptidoglycan degradation as the mode-of-action. Cell based screening of masarimycin against a panel of autolysin mutants, identified a higher MIC against a ΔlytB strain lacking an endo-N-acetylglucosaminidase involved in cell division. Subsequent biochemical and phenotypic analyses suggested that the higher MIC was due to an indirect interaction with LytB. Further analysis of changes to the cell surface in masarimycin treated cells identified the overexpression of several moonlighting proteins, including elongation factor Tu which is implicated in regulating cell shape. Checkerboard assays using masarimycin in concert with additional antibiotics identified an antagonistic relationship with the cell wall targeting antibiotic fosfomycin, which further supports a cell wall mode-of-action.


Asunto(s)
Peptidoglicano , Streptococcus pneumoniae , Antibacterianos/metabolismo , Antibacterianos/farmacología , Pared Celular/metabolismo , Diamida/metabolismo , N-Acetil Muramoil-L-Alanina Amidasa/genética , N-Acetil Muramoil-L-Alanina Amidasa/metabolismo , Peptidoglicano/metabolismo , Streptococcus pneumoniae/metabolismo
4.
Chembiochem ; 23(6): e202100532, 2022 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-34618387

RESUMEN

Yariv reagents are glycosylated triphenylazo dyes that bind to arabinogalactan proteins (AGPs), proteoglycans found in plant cell walls that are integral for plant growth and development. Yariv reagents are widely utilized as imaging, purification, and quantification tools for AGPs and represent the only small molecule probe for interrogating AGP function. The ability of Yariv reagents to bind to AGPs is dependent on the structure of the terminal glycoside on the dye. The reason for this selectivity has not been understood until the present work. Using circular dichroism spectroscopy, we show that the Yariv reagents form supramolecular aggregates with helical chirality. More significantly, the ability of the Yariv reagent to bind AGPs is correlated with this helical chirality. This finding paves the way towards developing a more detailed understanding of the nature of the Yariv-AGP complex, and the design of AGP-binding reagents with higher affinities and selectivities.


Asunto(s)
Glucósidos , Floroglucinol , Pared Celular/metabolismo , Glucósidos/metabolismo , Glicósidos/metabolismo , Floroglucinol/análogos & derivados , Floroglucinol/metabolismo , Proteínas de Plantas/metabolismo
5.
Bus Horiz ; 65(3): 267-275, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36062237

RESUMEN

The COVID-19 pandemic that erupted in 2020 forced businesses across the world to adopt virtual meetings. With many people working from home, software platforms like Zoom and Teams became ubiquitous, but their widespread use also revealed many weaknesses and limitations. While technologies for virtual meetings have existed for decades, these technologies have advanced significantly in recent years, and today range from audioconference facilities to telepresence rooms with high-resolution video and sophisticated virtual presence features. The available alternatives differ significantly in costs, complexity and capabilities, and choosing the most effective technology for each meeting setting is not always easy. This is important, since after the pandemic, virtual meetings will move from being a necessity brought on by the pandemic to being a widely accepted alternative to traditional face-to-face meetings. Consequently, the questions of when and how to meet virtually will become even more significant. In this article, we describe a decision-making framework for choosing when and how to meet virtually, based on matching the appropriate communication capabilities with various meeting objectives and taking into account meeting size and duration. The framework is based on extensive empirical research conducted in partnership with several major U.S. and European companies.

6.
Phys Chem Chem Phys ; 23(38): 21934-21940, 2021 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-34568885

RESUMEN

We report the use of saturation transfer difference (STD) NMR spectroscopy to observe the interaction of various phenylboronic acids (PBAs) with synthetic glycopolymers presenting galactose and glucose. After optimizing experimental parameters to maximize spin diffusion within the glycopolymers, STD NMR experiments were successfully used to detect binding of PBAs to the polymers. Amplification factor build-up curves in conjunction with differential epitope mapping experiments were used to generate an epitope map for the bound boronic acids. STD NMR was also used to detect the interaction between indole and a galactosylated glycopolymer, providing an indole-based view of this CH-π interaction, a common binding motif in carbohydrate recognition.


Asunto(s)
Ácidos Borónicos/química , Glicósidos/química , Simulación de Dinámica Molecular , Polímeros/química , Sitios de Unión , Ligandos , Espectroscopía de Resonancia Magnética , Estructura Molecular
7.
J Org Chem ; 85(24): 16236-16242, 2020 12 18.
Artículo en Inglés | MEDLINE | ID: mdl-33084327

RESUMEN

Yariv reagents are glycoconjugate tris-azo dyes widely used in plant biology. These reagents are synthesized by diazo coupling between phloroglucinol and a para-diazophenyl glycoside. Despite their synthetic accessibility, well-defined protocols for obtaining pure Yariv reagents, and their complete compound characterization data, have not been reported. We report here optimized protocols used to synthesize, purify, and characterize a panel of six Yariv reagents and suggest approaches that could be valuable for the purification and characterization of other glycoconjugates as well.

8.
Clin Transplant ; 28(9): 990-4, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24954160

RESUMEN

INTRODUCTION: Previously, increasing age has been a part of the exclusion criteria used when determining eligibility for a pancreas transplant. However, the analysis of pancreas transplantation outcomes based on age groupings has largely been based on single-center reports. METHODS: A UNOS database review of all adult pancreas and kidney-pancreas transplants between 1996 and 2012 was performed. Patients were divided into groups based on age categories: 18-29 (n = 1823), 30-39 (n = 7624), 40-49 (n = 7967), 50-59 (n = 3160), and ≥60 (n = 280). We compared survival outcomes and demographic variables between each age grouping. RESULTS: Of the 20 854 pancreas transplants, 3440 of the recipients were 50 yr of age or above. Graft survival was consistently the greatest in adults 40-49 yr of age. Graft survival was least in adults age 18-29 at one-, three-, and five-yr intervals. At 10- and 15-yr intervals, graft survival was the poorest in adults >60 yr old. Patient survival and age were found to be inversely proportional; as the patient population's age increased, survival decreased. CONCLUSION: Pancreas transplants performed in patients of increasing age demonstrate decreased patient and graft survival when compared to pancreas transplants in patients <50 yr of age.


Asunto(s)
Envejecimiento/fisiología , Supervivencia de Injerto/fisiología , Trasplante de Riñón , Trasplante de Páncreas , Adolescente , Adulto , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Trasplante de Riñón/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Trasplante de Páncreas/estadística & datos numéricos , Pronóstico , Sistema de Registros , Donantes de Tejidos , Obtención de Tejidos y Órganos , Adulto Joven
9.
Clin Transplant ; 28(8): 883-8, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24930804

RESUMEN

Venous jump grafts are used in pancreas transplantation to salvage a pancreas with a short portal vein or to facilitate an easier anastomosis. There have been no large studies evaluating the safety of venous jump grafts in pancreas transplantation. We analyzed the UNOS database to determine whether venous jump grafts are associated with graft loss or patient death. Data from UNOS on all adult pancreas transplant recipients 1996-2012 were analyzed. Venous extension grafts were used in 2657 cases; they were not in 18 124. Kaplan-Meier/product-limit estimates analysis demonstrated similar patient survival (p < 0.641) and death-censored graft survival (p < 0.351) at one, three, five,10, and 15 yr between subjects with and without venous jump grafts. There was a statistically significant difference in one-yr unadjusted patient survival between the venous extension graft (94.9%) and the no-venous extension graft (95.8%) groups (p < 0.045) and a borderline difference in one-yr graft survival between the venous extension graft (84.1%) and the no-venous extension graft (82.6%) groups (p < 0.055). There was no significant difference in patient survival or allograft survival at the three-, five-, 10-, and 15-yr intervals. The use of venous jump grafts is not associated with increased graft loss or mortality.


Asunto(s)
Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Trasplante de Páncreas , Enfermedades Pancreáticas/cirugía , Vena Porta/trasplante , Trombosis de la Vena/mortalidad , Adulto , Anastomosis Quirúrgica , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Enfermedades Pancreáticas/mortalidad , Pronóstico , Factores de Riesgo , Tasa de Supervivencia , Trasplante Homólogo
10.
Beilstein J Org Chem ; 10: 2658-63, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25550728

RESUMEN

Galactans ranging in length from one to five residues were prepared in a single step by treatment of the glycosyl donor 2,3,4-tri-O-benzoyl-ß-D-galactopyranosyl fluoride with lanthanum perchlorate in the presence of an initiator alcohol. The product oligosaccharides were readily chromatographically separable. This oligomerization was used to synthesize a pentagalactan in a single step from monosaccharide building blocks in reasonable overall yields.

11.
Sci Rep ; 14(1): 11097, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750043

RESUMEN

Assembling atomic layers of van der Waals materials (vdW) combines the physics of two materials, offering opportunities for novel functional devices. Realization of this has been possible because of advancements in nanofabrication processes which often involve chemical processing of the materials under study; this can be detrimental to device performance. To address this issue, we have developed a modified micro-manipulator setup for cryogenic exfoliation, pick up, and transfer of vdW materials to assemble heterostructures. We use the glass transition of a polymer PDMS to cleave a flake into two, followed by its pick-up and drop to form pristine twisted junctions. To demonstrate the potential of the technique, we fabricated twisted heterostructure of Bi2Sr2CaCu2O8+x (BSCCO), a van der Waals high-temperature cuprate superconductor. We also employed this method to re-exfoliate NbSe2 and make twisted heterostructure. Transport measurements of the fabricated devices indicate the high quality of the artificial twisted interface. In addition, we extend this cryogenic exfoliation method for other vdW materials, offering an effective way of assembling heterostructures and twisted junctions with pristine interfaces.

12.
Beilstein J Org Chem ; 9: 608-12, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23616802

RESUMEN

Functionalizable monotelechelic polymers are useful materials for chemical biology and materials science. We report here the synthesis of a capping agent that can be used to terminate polymers prepared by ring-opening metathesis polymerization of norbornenes bearing an activated ester. The terminating agent is a cis-butene derivative bearing a Teoc (2-trimethylsilylethyl carbamate) protected primary amine. Post-polymerization modification of the polymer was accomplished by amidation with an azido-amine linker followed by Cu(I)-catalyzed azide-alkyne cycloaddition with propargyl sugars. Subsequent Teoc deprotection and conjugation with pyrenyl isothiocyanates afforded well-defined end-labeled glycopolymers.

13.
Bioconjug Chem ; 23(6): 1166-73, 2012 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-22551003

RESUMEN

The carbohydrates galactose and 3-sulfogalactose, found on sphingolipids in myelin, interact with each other via a carbohydrate-carbohydrate interaction (CCI). In oligodendrocytes, this interaction triggers a signaling cascade resulting in cytoskeletal rearrangements and reorganization of glycolipids and proteins at the cellular surface. These rearrangements can also be triggered by synthetic multivalent glycoconjugates. In this report, we describe the synthesis of glycan-coated silica nanoparticles and their subsequent binding to cultured oligodendrocytes and purified myelin. Fluorescent silica nanoparticles with an azidosiloxane-derived outer shell were functionalized with carbohydrates using the copper-promoted azide-alkyne cycloaddition reaction. The carbohydrate-carbohydrate interaction between galactose and 3-sulfogalactose was examined by measuring the binding of 3-sulfogalactose-containing nanoparticles to galactolipids that had been immobilized in a multiwell plate. Particle aggregation mediated by CCI was observed by TEM. The interaction of the particles with oligodendrocytes and purified myelin was examined using fluorescence microscopy, providing direct evidence for binding of galactose and 3-sulfogalactose-coated nanoparticles to oligodendrocytes and myelin fragments.


Asunto(s)
Colorantes Fluorescentes/química , Galactosa/análogos & derivados , Galactosa/metabolismo , Nanopartículas/química , Polisacáridos/química , Dióxido de Silicio/química , Animales , Células Cultivadas , Colorantes Fluorescentes/metabolismo , Glucolípidos/metabolismo , Humanos , Vaina de Mielina/metabolismo , Nanopartículas/metabolismo , Nanopartículas/ultraestructura , Oligodendroglía/metabolismo , Polisacáridos/metabolismo , Dióxido de Silicio/metabolismo
14.
BMC Nephrol ; 11: 5, 2010 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-20359353

RESUMEN

BACKGROUND: The beneficial effects of early statin use in kidney transplant recipients, especially those on tacrolimus-based immunosuppression, are not well established. We evaluated the predictors of statin use following kidney transplantation and examined its association with patient and allograft survival. METHODS: We examined 615 consecutive patients who underwent kidney transplant at our institution between January 1998 and January 2002. Statin use was assessed at baseline and 3, 6, 9, and 12 months following kidney transplant. Patients were followed for allograft and patient survival. RESULTS: 36% of the 615 kidney transplant recipients were treated with statin treatment. Statin use increased over the course of the study period. Older age, elevated body mass index, higher triglyceride levels, hypercholesterolemia, diabetes, history of myocardial infarction were associated with higher rates of statin use; elevated alkaline phosphatase levels and CMV IgG seropositivity were associated with less statin use. Older age, elevated BMI and hypercholesterolemia remained significant predictors of increased statin use after accounting for covariates using multiple regression. The early use of statins was not associated with improvements in unadjusted patient survival [HR 0.99; 95%CI 0.72-1.37] or graft survival [HR 0.97; 95% CI 0.76-1.24]. The risks of death and graft survival were not consistently reduced with exposure to statin using either adjusted models or propensity scores in Cox Proportional Hazards models. CONCLUSIONS: In a kidney transplant population primarily receiving tacrolimus-based immunosuppression, early statin use was not associated with significantly improved graft or patient survival.


Asunto(s)
Supervivencia de Injerto/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inmunosupresores/uso terapéutico , Trasplante de Riñón/mortalidad , Tacrolimus/uso terapéutico , Adulto , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Organización y Administración , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Factores de Riesgo , Trasplante Homólogo
15.
J Am Chem Soc ; 131(16): 5718-9, 2009 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-19351114

RESUMEN

Hollow nanoscale polymer capsules have found wide applications in drug delivery and catalysis. The use of nanocapsules and related materials for drug delivery, as nanoreactors, or as platforms for chemical separations requires control over cargo entry and exit and installation of diverse chemical functionality in the capsule interior. Despite the diversity of methods for nanocapsule preparation, methods for efficiently functionalizing the core of hollow nanocapsules are scarce. We report here a versatile and modular approach for the synthesis of hollow polymeric capsules that can be readily and diversely functionalized in the core. Capsules functionalized with pyrene, ferrocene, amines, and carboxylic acids have been prepared. The capsules are characterized using dynamic light scattering, fluorescence spectroscopy, and transmission electron microscopy. These core functionalized capsules can selectively extract hydrophilic cationic or anionic dyes into organic solutions based on the charge complementarity of the core functionality. The synthetic approach described here is modular and permits facile control of the interior as well as exterior properties of the nanocapsules.


Asunto(s)
Portadores de Fármacos/síntesis química , Nanocápsulas/química , Nanotecnología/métodos , Polímeros/síntesis química , Aminas/síntesis química , Aminas/química , Ácidos Carboxílicos/síntesis química , Ácidos Carboxílicos/química , Colorantes/química , Colorantes/aislamiento & purificación , Colorantes/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Compuestos Ferrosos/síntesis química , Compuestos Ferrosos/química , Humanos , Luz , Metalocenos , Nanocápsulas/ultraestructura , Polímeros/química , Pirenos/síntesis química , Pirenos/química , Dispersión de Radiación , Espectrometría de Fluorescencia
16.
Mod Pathol ; 22(11): 1468-76, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19734851

RESUMEN

Peritubular capillary C4d staining in allograft kidney is an important criterion for antibody-mediated rejection. Whether BK virus infection can result in complement activation is not known. We studied 113 renal allograft biopsies from 52 recipients with a history of BK virus activation. The samples were classified into four groups according to the concurrent detection of BK virus DNA in urine, plasma, and/or biopsy: BK-negative (n=37), viruria (n=53), viremia (n=7), and nephropathy (n=16) groups. The histological semiquantitative peritubular capillary C4d scores in the viremia (0.3+/-0.8) and BK nephropathy (0.6+/-0.9) groups were lower than those in the BK-negative group (1.2+/-1.1, P=0.05 and P=0.06, respectively) and the viruria group (1.2+/-1.1, P=0.04 and P=0.06, respectively). Diffuse or focal peritubular capillary C4d staining was present in 9/76 (12%) and 14/76 (19%) of all samples with concurrent BK virus reactivation (viruria, viremia, and nephropathy). The diagnosis of antibody-mediated rejection could be established in 7/9 (78%) and 5/14 (36%) of these samples, respectively. Diffuse tubular basement membrane C4d staining was restricted to BK nephropathy cases (4/16, 25%). Semiquantitative tubular basement membrane C4d scores were higher in BK nephropathy (1.2+/-1.3) compared with BK-negative (0.05+/-0.3, P=0.017) and viruria (0.0+/-0.0, P=0.008) groups. Bowman's capsule C4d staining was more frequent in BK nephropathy (5/16) compared with the aforementioned groups (2/36 (P=0.023) and 4/51 (P=0.03), respectively). Within the BK nephropathy group, samples with tubular basement membrane stain had more infected tubular epithelial cells (12.1+/-7.6% vs 4.4+/-5.0%, P=0.03) and a trend toward higher interstitial inflammation scores. In conclusion, peritubular capillary C4d staining remains a valid marker for the diagnosis of antibody-mediated rejection in the presence of concurrent BK virus infection. A subset of biopsies with BK nephropathy shows tubular basement membrane C4d staining, which correlates with marked viral cytopathic effect.


Asunto(s)
Virus BK/metabolismo , Capilares/metabolismo , Complemento C4b/metabolismo , Riñón/metabolismo , Fragmentos de Péptidos/metabolismo , Infecciones por Polyomavirus/metabolismo , Infecciones Tumorales por Virus/metabolismo , Adolescente , Adulto , Anciano , Capilares/patología , Capilares/virología , Niño , Femenino , Humanos , Inmunohistoquímica , Riñón/irrigación sanguínea , Riñón/patología , Riñón/virología , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/patología , Infecciones por Polyomavirus/virología , Infecciones Tumorales por Virus/patología , Viremia/metabolismo , Viremia/patología , Viremia/virología , Activación Viral
17.
Clin Transplant ; 23(4): 525-31, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19681976

RESUMEN

BACKGROUND: Transplantation of kidneys from donor with arteriosclerosis seen on pre-implantation biopsy has not been well studied. METHODS: We retrospectively evaluated 20 dual kidney transplant (DKT) and 28 single (SKT) kidney transplant recipients with >or=12 months follow-up from donors with moderate arteriosclerosis (>or=25% luminal diameter narrowing). RESULTS: Death censored graft survival was 100% and 79%, respectively (p = 0.0339). DKT recipients had significantly lower mean creatinine levels at one, three, six, and nine months and spent somewhat less time on the waiting list (181 +/- 160 vs. 318 +/- 306 d, p = 0.1429). DKT patients received kidneys from significantly older donors (64 +/- 7 vs. 54 +/- 11 yr; p = 0.0012), proportionately more expanded criteria donors (95% vs. 54%; p = 0.0029), and more donors with hypertension (81% vs. 48%, p = 0.0344) and death related to cerebrovascular accident (100% vs. 71%, p = 0.0143); however, more DKT kidneys underwent machine perfusion (95% vs. 57%, p = 0.0068). Baseline recipient variables were comparable between the two groups including age, race, gender, retransplantation, and HLA mismatch. Pre-implant biopsy was notable for similar frequencies of moderate interstitial fibrosis (10% vs. 14%, respectively) and glomerulosclerosis. CONCLUSION: Among recipients of deceased-donor kidneys with >25% arteriosclerosis, short-term outcomes after DKT were superior to that of SKT grafts. This approach may help to expand the donor-organ pool while optimizing outcomes.


Asunto(s)
Arteriosclerosis , Glomérulos Renales/patología , Trasplante de Riñón/métodos , Donantes de Tejidos , Adulto , Anciano , Cadáver , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
18.
Cureus ; 11(7): e5091, 2019 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-31523526

RESUMEN

Aim We compared the outcomes of transplanting expanded criteria donor (ECD) kidneys undergoing machine perfusion (MP) versus cold storage (CS). Material and methods Data on all expanded criteria deceased donor kidney transplants performed at the University of Pittsburgh Medical Center from January 2003 through December 2012 were collected from an in-house electronic repository. There were 78 patients in the MP group and 101 patients in the CS group. The majority of the ECD kidneys were imported from other organ procurement organizations: 69 of 73 in the MP group (94.5%, 5 from unknown sources); and 90 of 99 in the CS group (91%), 2 from an unknown source). Most of the patients in the MP group (77 of 78) received a combination of MP and static CS. MP was performed just prior to transplantation in all MP patients. We used descriptive statistics to characterize our sample. We used logistic regression analysis to model the binary outcome of delayed graft function (DGF; i.e., "yes/no") and Cox (proportional hazard) regression to model time until graft failure. The Kaplan-Meier product-limit method was used to estimate survival curves for graft and patient survival. Results A total of 179 transplants were done from ECD donors (MP, 78; CS, 101). The mean static cold storage time was 14 ± 4.1 hours and the mean machine perfusion time was 11.2 ± 6.3 hours in the MP group. The donor creatinine was higher (1.3 ± 0.6 mg/dl vs. 1.2 ± 0.4 mg/dl, p = 0.01) and the cold ischemia time was longer (28.9 ± 10 hours vs. 24 ± 7.9 hours, p = 0.0003) in the MP patients. There were no differences between the two groups in DGF rate (20.8% [MP] vs. 25.8% [CS], p = 0.46), six-year patient survival (74% [MP] vs. 63.2% [CS], p = 0.11), graft survival (64.3% [MP] vs. 51.5% [CS], p = 0.22), and serum creatinine levels (1.5 mg/dl vs. 1.5 mg/dl) on univariate analysis. On unadjusted analysis, MP subjects without DGF had longer graft survival compared to CS subjects with DGF (p < 0.0032) and MP subjects with DGF (p < 0.0005). MP subjects without DGF had longer death-censored graft survival compared to CS subjects with DGF (p < 0.0077) and MP subjects with DGF (p < 0.0016). However, on regression analysis, MP subjects had longer graft survival than CS subjects when DGF was not present. MP subjects without DGF had longer patient survival compared to CS subjects with DGF (p < 0.0289), on unadjusted analysis. MP subjects had a reduced risk of graft failure (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.17, 0.68) and death-censored graft failure (HR, 0.44; 95% CI, 0.19, 1.00), compared to CS subjects when DGF was not present. Conclusions Reduction of DGF rates for imported ECD kidneys is vital to optimize outcomes and increase their utilization. One strategy to decrease DGF rates may be to reduce static CS time during transportation, by utilizing a portable kidney perfusion machine.

19.
Mod Pathol ; 21(12): 1490-8, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18820671

RESUMEN

Diffuse C4d deposition in peritubular capillaries is a well-recognized marker of antibody-mediated rejection. The significance of staining patterns that are focal or affect non-peritubular capillary compartments is less well defined. Paired frozen section and paraffin-embedded tissue stains were performed in 52 kidney allograft biopsies, and correlated with clinicopathologic parameters. Diffuse peritubular capillary C4d deposits were more often seen in frozen sections (22/52, 43% frozen tissue vs 10/52, 19% paraffin-embedded tissue), whereas focal staining was observed more frequently within paraffin sections (13/52, 25% paraffin-embedded tissue vs 7/52, 14% frozen tissue). In biopsies taken from patients with a history of donor-specific antibodies, diffuse, focal and negative peritubular capillary C4d staining patterns were seen in 11/14 (79%), 1/14 (7%) and 2/14 (14%) of frozen biopsies vs 5/14 (36%), 6/14 (43%) and 3/14 (21%) of paraffin-embedded biopsies. Transplant glomerulopathy score in paraffin-embedded biopsies was higher in specimens with vs without glomerular basement membrane C4d staining (1.5+/-0.8 vs 1.0+/-0.6, P=0.03). Tubular basement membrane staining was present in 4% paraffin-embedded and 48% frozen specimens independent of tubular atrophy. Arteriolar hyalinosis score in paraffin-embedded specimens was higher in biopsies with vs those without arteriolar C4d deposits (1.3+/-0.9 vs 0.9+/-0.8, P=0.04). Arterial staining was unrelated to the degree of intimal thickening. In conclusion, peritubular capillary deposits correlate well with circulating donor-specific antibody. For paraffin-embedded tissue, combining the results of focal and diffuse staining allows a diagnostic sensitivity comparable to diffuse staining in frozen tissue. Finally, C4d deposits preferentially in lesions of chronic transplant glomerulopathy and arteriolar hyalinosis.


Asunto(s)
Complemento C4b/metabolismo , Rechazo de Injerto/inmunología , Trasplante de Riñón/inmunología , Fragmentos de Péptidos/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Capilares/metabolismo , Capilares/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Secciones por Congelación , Membrana Basal Glomerular/irrigación sanguínea , Membrana Basal Glomerular/metabolismo , Membrana Basal Glomerular/patología , Rechazo de Injerto/patología , Humanos , Isoanticuerpos/sangre , Isoantígenos/inmunología , Túbulos Renales/irrigación sanguínea , Túbulos Renales/metabolismo , Túbulos Renales/patología , Masculino , Persona de Mediana Edad , Adhesión en Parafina , Sensibilidad y Especificidad , Trasplante Homólogo
20.
Transplantation ; 86(2): 264-8, 2008 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-18645489

RESUMEN

BACKGROUND: Kidney transplantation from small pediatric donors is being performed with increased frequency as single (SK) or en bloc (EBK) kidneys. METHODS: Between 2002 and 2006, 19 EBK and 14 SK transplants from pediatric donors less than or equal to 15 kg were performed. SK arterial anastomoses were performed to the aortic patch (n=8), aortic conduit (n=1), or renal artery orifice (n=5). RESULTS: En bloc kidney donors were on average younger (12+/-10 vs. 24+/-8 months, respectively; P=0.0102) and weighed less (10+/-3 vs. 13+/-3, respectively; P=0.0184). There were no differences between the two groups in recipient age, race, body mass index, degree of sensitization, retransplantation, and cold ischemia time; however, EBK recipients were somewhat better matched at the human leukocyte antigen DR locus (P=0.0515). Delayed graft function was more frequent in the SK group (25% vs. 0%; P=0.0542). Acute rejection occurred in 21% of recipients in both groups. Glomerular filtration rates were significantly higher with EBK than SK at 12-months posttransplantation. At 1 year, graft survival for SK and EBK was 86% and 79%, respectively (P=1.000). Graft thrombosis occurred in 0% (0/9) of SK recipients in which an aortic cuff or conduit was used, 40% (2/5) of SK recipients without an aortic cuff, and 5% (1/19) of EBK recipients (P=0.03). CONCLUSION: Short-term outcomes of kidneys from small pediatric donors are satisfactory when transplanted as SKs or en bloc; however, the absence of an aortic patch in SK transplantation is a risk factor for early thrombosis.


Asunto(s)
Fallo Renal Crónico/terapia , Trasplante de Riñón/métodos , Índice de Masa Corporal , Peso Corporal , Cadáver , Preescolar , Creatinina/metabolismo , Femenino , Supervivencia de Injerto , Antígenos HLA/metabolismo , Humanos , Lactante , Fallo Renal Crónico/etiología , Masculino , Preservación de Órganos , Donantes de Tejidos
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