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1.
Rev Sci Instrum ; 92(5): 054502, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34243344

RESUMO

We describe a torsion pendulum with a large mass-quadrupole moment and a resonant frequency of 2.8 mHz, whose angle is measured using a Michelson interferometer. The system achieved noise levels of ∼200prad/Hz between 0.2 and 30 Hz and ∼10prad/Hz above 100 Hz. Such a system can be applied to a broad range of fields from the study of rotational seismic motion and elastogravity signals to gravitational wave observation and tests of gravity.

2.
Sci Adv ; 6(19): eaba5337, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32494727

RESUMO

Suprastructures at the colloidal scale must be assembled with precise control over local interactions to accurately mimic biological complexes. The toughest design requirements include breaking the symmetry of assembly in a simple and reversible fashion to unlock functions and properties so far limited to living matter. We demonstrate a simple experimental technique to program magnetic field-induced interactions between metallodielectric patchy particles and isotropic, nonmagnetic "satellite" particles. By controlling the connectivity, composition, and distribution of building blocks, we show the assembly of three-dimensional, multicomponent supraparticles that can dynamically reconfigure in response to change in external field strength. The local arrangement of building blocks and their reconfigurability are governed by a balance of attraction and repulsion between oppositely polarized domains, which we illustrate theoretically and tune experimentally. Tunable, bulk assembly of colloidal matter with predefined symmetry provides a platform to design functional microstructured materials with preprogrammable physical and chemical properties.

3.
Phys Rev Lett ; 124(10): 101101, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32216404

RESUMO

We tested the gravitational 1/r^{2} law using a stationary torsion-balance detector and a rotating attractor containing test bodies with both 18-fold and 120-fold azimuthal symmetries that simultaneously tests the 1/r^{2} law at two different length scales. We took data at detector-attractor separations between 52 µm and 3.0 mm. Newtonian gravity gave an excellent fit to our data, limiting with 95% confidence any gravitational-strength Yukawa interactions to ranges <38.6 µm.

4.
Ann Oncol ; 30(7): 1104-1113, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30977778

RESUMO

BACKGROUND: Immune checkpoint blockade with Programmed cell death 1 (PD-1)/PD-L1 inhibitors has been effective in various malignancies and is considered as a standard treatment modality for patients with non-small-cell lung cancer (NSCLC). However, emerging evidence show that PD-1/PD-L1 blockade can lead to hyperprogressive disease (HPD), a flair-up of tumor growth linked to dismal prognosis. This study aimed to evaluate the incidence of HPD and identify the determinants associated with HPD in patients with NSCLC treated with PD-1/PD-L1 blockade. PATIENTS AND METHODS: We enrolled patients with recurrent and/or metastatic NSCLC treated with PD-1/PD-L1 inhibitors between April 2014 and November 2018. Clinicopathologic variables, dynamics of tumor growth, and treatment outcomes were analyzed in patients with NSCLC who received PD-1/PD-L1 blockade. HPD was defined according to tumor growth kinetics (TGK), tumor growth rate (TGR), and time to treatment failure (TTF). Immunophenotyping of peripheral blood CD8+ T lymphocytes was conducted to explore the potential predictive biomarkers of HPD. RESULTS: A total of 263 patients were analyzed. HPD was observed in 55 (20.9%), 54 (20.5%), and 98 (37.3%) patients according to the TGK, TGR, and TTF. HPD meeting both TGK and TGR criteria was associated with worse progression-free survival [hazard ratio (HR) 4.619; 95% confidence interval (CI) 2.868-7.440] and overall survival (HR, 5.079; 95% CI, 3.136-8.226) than progressive disease without HPD. There were no clinicopathologic variables specific for HPD. In the exploratory biomarker analysis with peripheral blood CD8+ T lymphocytes, a lower frequency of effector/memory subsets (CCR7-CD45RA- T cells among the total CD8+ T cells) and a higher frequency of severely exhausted populations (TIGIT+ T cells among PD-1+CD8+ T cells) were associated with HPD and inferior survival rate. CONCLUSION: HPD is common in NSCLC patients treated with PD-1/PD-L1 inhibitors. Biomarkers derived from rationally designed analysis may successfully predict HPD and worse outcomes, meriting further investigation of HPD.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/imunologia , Metástase Linfática , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Carga Tumoral
5.
Transplant Proc ; 50(10): 3748-3755, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577266

RESUMO

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) can lead to life-threatening outcomes with rapid spread of the carbapenemase gene in solid organ transplantation (SOT) recipients because of limitations of available antibiotics. We examined the characteristics and importance of CPE acquisition in SOT recipients with large numbers of CPE isolates. METHODS: Between November 2015 and October 2016, 584 CPE isolates were found in 37 recipients and verified by carbapenemase gene multiplex polymerase chain reaction (PCR). One hundred recipients with at least 2 negative results in carbapenemase PCR for stool surveillance and no CPE isolates in clinical samples were retrospectively included. RESULTS: Most CPE isolates were Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (546, 93.5%). The most frequent transplantation organ was lung (43.3%), and the most common sample with CPE isolates other than stool was respiratory tract (22.6%). The median time between SOT and first CPE acquisition was 7 days. All-cause mortality was significantly higher in recipients with CPE than in those without CPE (24.3% vs 10.0%; P = .03). In multivariate regression analysis, stool colonization of vancomycin-resistant Enterococci and/or Clostridium difficile during 30 days before SOT (odds ratio [OR], 3.28; 95% CI, 1.24-8.68; P = .02), lung transplantation (OR, 4.50; 95% CI, 1.19-17.03; P = .03), and intensive care unit stay ≥2 weeks (OR, 6.21; 95% CI, 1.72-22.45; P = .005) were associated with acquisition of CPE. CONCLUSIONS: Early posttransplantation CPE acquisition may affect the clinical outcome of SOT recipients. Careful screening for CPE during the early posttransplantation period would be meaningful in recipients with risk factors.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae/etiologia , Transplante de Órgãos/efeitos adversos , Transplantados , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , beta-Lactamases/biossíntese , beta-Lactamases/genética
6.
Transplant Proc ; 50(10): 3887-3894, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577282

RESUMO

In clinical islet transplantation, hepatic ischemia and insufficient neovascularization of transplanted islets are barriers to islet survival and function. However, hepatocytes have a potency to protect themselves against ischemia. We hypothesized that ischemia/reperfusion preconditioning (IRP) of hepatocytes might beneficially affect islet cells in a coculture system. Primary islets were cocultured with primary hepatocytes, and hepatocyte IRP was conducted by subjecting cells to hypoxic conditions for single 15-minute/30-minute hypoxia, or 2 tandem 15-minute/30-minute hypoxic treatments (hypoxic-normoxic-hypoxic). We show that gene expression levels of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), transforming growth factor-α (TGF-α), and TGF-ß1 in hepatocytes were increased by IRP. IRP hepatocytes secreted hepatocyte growth factor and insulin-like growth factor-1. Coculture of islets with IRP hepatocytes enhanced islet insulin secretion in glucose challenge test and expression of the survival-related gene Bcl-2 and the regenerating gene-1α (Reg-1α). Islets cocultured with the 30-minute double-IRP hepatocytes displayed significantly higher viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase dUTP nick end labeling stain compared with that of islets subjected to 30 minutes of hypoxia. These results suggest that islet coculture with IRP hepatocytes can improve islet survival and insulin secretion.


Assuntos
Hepatócitos/citologia , Precondicionamento Isquêmico/métodos , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/citologia , Animais , Sobrevivência Celular , Técnicas de Cocultura , Fator de Crescimento de Hepatócito/metabolismo , Hepatócitos/metabolismo , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo
7.
Transplant Proc ; 50(9): 2759-2763, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30401392

RESUMO

BACKGROUND: The Korean Organ Transplantation Registry (KOTRY) began to register lung transplants in 2015. This is an initial report on the status of patients receiving lung transplants over the past 2 years. METHODS: We analyzed a total of 69 patients who received lung transplants in 2015 and 2016 and who registered with the KOTRY. RESULTS: The 69 patients were treated in 5 institutions. The average (SD) donor age was 39.2 (12.6) years; there were 40 male patients. The average (SD) recipient age was 55.7 (10.0) years, and the number of male recipients was 46. A total of 66 patients underwent bilateral lung transplantation, 3 underwent single-lung transplantation, and 1 underwent simultaneous heart-lung transplantation. The most frequent indication for lung transplantation was idiopathic pulmonary fibrosis (35 patients), followed by connective tissue disease-related interstitial lung disease (9) and acute respiratory failure (8). Prior to transplantation, 23 patients required ventilator care, and 12 required extracorporeal membrane oxygenation while on the waiting list. Episodes of acute rejection during follow-up were reported in 4, 2, 1, and 1 patients at 3, 6, 9, and 12 months, respectively. Infections requiring hospitalization were reported in 27, 10, 4, and 3 patients at 3, 6, 9, and 12 months, respectively. CONCLUSION: The establishment of KOTRY renders it possible to collect nationwide data on lung transplantation, improving research on the topic and clarifying clinical feasibility.


Assuntos
Transplante de Pulmão/estatística & dados numéricos , Sistema de Registros , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Doadores de Tecidos
8.
Transplant Proc ; 50(4): 1056-1062, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29731065

RESUMO

INTRODUCTION: B cell subtypes and immunoglobulin variable (V), diversity (D), joining (J) gene segment usage of B cell receptors in ABO-incompatible (ABOi) kidney transplantation (KT) in comparison to ABO-compatible KT have not been studied. The aims of this study were to analyze the VDJ gene segment usages of B cell receptors in peripheral blood of ABOi KT recipients. METHODS: Eighteen ABOi KT patients with accommodation (ABOiA), 10 ABO-compatible stable KT patients (ABOcS), and 10 ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at day 10 after transplantation were selected. Complete transcriptomes of their peripheral blood samples were sequenced and analyzed through RNA sequencing. RESULTS: By family, immunoglobulin heavy chain variable 3 (IGHV3), immunoglobulin light kappa chain variable 1 (IGKV1), immunoglobulin light lambda chain variable 2 (IGLV2), and immunoglobulin light lambda chain joining 3 (IGLJ3) gene segments were most frequently used in all groups, and their usage was not statistically different among the three groups except for IGHV3 and IGKV1. IGKV1 was more frequently used in the ABOiA group than in the ABOcS group. According to individual gene segments, IGHV3-7, IGHV3-15, IGHV4-59, IGKV3-11, IGLV1-44, IGLV2-14, IGLV4-69, and IGLV7-46 were more frequently used in the ABOcS group than other groups, and IGKV3-7 was more frequently used in the ABOiR group than other groups. IGLV5-52 and IGLV7-43 were more frequently used in the ABOiA group than in ABOcS group. CONCLUSIONS: Our findings suggest that RNA sequencing transcriptomic analyses of peripheral blood can provide information on the VDJ gene usage of B cell receptors and the mechanisms of accommodation and immune reaction in ABOi KT.


Assuntos
Incompatibilidade de Grupos Sanguíneos/imunologia , Rejeição de Enxerto/imunologia , Transplante de Rim , Receptores de Antígenos de Linfócitos B/imunologia , Éxons VDJ/genética , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Feminino , Perfilação da Expressão Gênica , Genes de Cadeia Pesada de Imunoglobulina , Humanos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade
9.
Transplant Proc ; 50(8): 2363-2367, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29801964

RESUMO

BACKGROUND: The shortage of donor organs has been a major challenge in transplantation. In an effort to reduce the donor shortage, kidney transplantation (KT) using expanded criteria donors (ECD) was encouraged. In Korea, transplantation centers used the Korea Network for Organ Sharing (KONOS) ECD criteria, which is different from the United Network for Organ Sharing (UNOS) criteria. The aim of this study is to evaluate the predictive power of KONOS criteria on delayed graft function (DGF) in comparison to UNOS criteria. METHODS: A total of 376 recipients who underwent deceased donor kidney transplantation between January 2005 and December 2014 at Severance Hospital were retrospectively reviewed. Of these, 130 cases satisfied KONOS ECD, while the others followed KONOS standard criteria donor (SCD). RESULTS: Donor age and history of hypertension was significantly higher with KONOS ECD than with KONOS SCD. In KONOS subgroup analysis, donor characteristics were different than with UNOS criteria. The incidence of DGF was higher in the KONOS ECD group than in the KONOS SCD group. However, UNOS ECD showed a high incidence of DGF compared to UNOS SCD with the same KONOS criteria. UNOS ECD was an independent risk factor for DGF in multivariate analysis. However, KONOS ECD was not a risk factor for DGF. Although glomerular filtration rate was inferior in the KONOS ECD group compared to the KONOS SCD group, the UNOS SCD group within the KONOS ECD group showed similar graft function compared to the KONOS SCD group. CONCLUSION: KONOS criteria have a lower predictive power for DGF than UNOS criteria.


Assuntos
Função Retardada do Enxerto/epidemiologia , Transplante de Rim/métodos , Doadores de Tecidos/provisão & distribuição , Adulto , Função Retardada do Enxerto/etiologia , Feminino , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , República da Coreia , Estudos Retrospectivos , Fatores de Risco
11.
Transplant Proc ; 49(5): 1165-1169, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28583549

RESUMO

Sirolimus (SRL), a mammalian target of rapamycin inhibitor, is widely used in transplantation, but the mechanisms whereby it induces adverse effects, such as proteinuria and edema, remain unclear. To determine whether isolated SRL induces proteinuria or not, the authors intraperitoneally injected C57BL/6 mice with different doses of SRL (0 mg/[kg·d], 3 mg/[kg·d], 10 mg/[kg·d], or 30 mg/[kg·d]) for 24 days. Urinary albumin excretion was then quantified using a double-sandwich enzyme-linked immunosorbent assay, and serum creatinine levels were measured using a single dry-film chemistry auto-analyzer. The mRNA expression levels of various genes were also measured by polymerase chain reaction. Urinary albumin was not detected in the SRL-treated mice, but serum creatinine levels were found to increase dose-dependently and were significantly higher in the animals treated with 30 mg/kg of SRL than in untreated controls. Glomerular mRNA expression profiling showed down-regulations of podocyte-related genes (Wilms tumor 1, synaptopodin, nephrin, CD2-associated protein, and podocin) and of transforming growth factor-beta (a marker of fibrosis) in sirolimus-treated mice. In addition, expressions of the antiapoptotic genes Bcl-2 and Bcl-xL were also down-regulated. Furthermore, the protein levels of these genes in mice kidney were also decreased by sirolimus. Although sirolimus treatment reduced the expressions of slit diaphragm-associated molecules and increased serum creatinine levels, it failed to induce proteinuria. Our findings indicate that proteinuria is not induced by isolated SRL treatment. Further studies are required to identify conditions in which sirolimus induces proteinuria.


Assuntos
Imunossupressores/toxicidade , Rim/efeitos dos fármacos , Proteinúria/induzido quimicamente , Sirolimo/toxicidade , Animais , Masculino , Camundongos Endogâmicos C57BL
12.
Ann Oncol ; 28(6): 1250-1259, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28460066

RESUMO

BACKGROUND: We conducted co-clinical trials in patient-derived xenograft (PDX) models to identify predictive biomarkers for the multikinase inhibitor dovitinib in lung squamous cell carcinoma (LSCC). METHODS: The PDX01-02 were established from LSCC patients enrolled in the phase II trial of dovitinib (NCT01861197) and PDX03-05 were established from LSCC patients receiving surgery. These five PDX tumors were subjected to in vivo test of dovitinib efficacy, whole exome sequencing and gene expression profiling. RESULTS: The PDX tumors recapitulate histopathological properties and maintain genomic characteristics of originating tumors. Concordant with clinical outcomes of the trial enrolled-LSCC patients, dovitinib produced substantial tumor regression in PDX-01 and PDX-05, whereas it resulted in tumor progression in PDX-02. PDX-03 and -04 also displayed poor antitumor efficacy to dovitinib. Mutational and genome-wide copy number profiles revealed no correlation between genomic alterations of FGFR1-3 and sensitivity to dovitinib. Of note, gene expression profiles revealed differentially expressed genes including FGF3 and FGF19 between PDX-01 and 05 and PDX-02-04. Pathway analysis identified two FGFR signaling-related gene sets, FGFR ligand binding/activation and SHC-mediated cascade pathway were substantially up-regulated in PDX-01 and 05, compared with PDX-02-04. The comparison of gene expression profiles between dovitinib-sensitive versus -resistant lung cancer cell lines in the Cancer Cell Line Encyclopedia database also found that transcriptional activation of 18 key signaling components in FGFR pathways can predict the sensitivity to dovitinib both in cell lines and PDX tumors. These results highlight FGFR pathway activation as a key molecular determinant for sensitivity to dovitinib. CONCLUSIONS: FGFR gene expression signatures are predictors for the response to dovitinib in LSCC.


Assuntos
Benzimidazóis/uso terapêutico , Biomarcadores/sangue , Carcinoma de Células Escamosas/tratamento farmacológico , Ensaios Clínicos como Assunto , Neoplasias Pulmonares/tratamento farmacológico , Quinolonas/uso terapêutico , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Carcinoma de Células Escamosas/genética , Humanos , Neoplasias Pulmonares/genética , Mutação , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Sequenciamento do Exoma
13.
Clin Transl Sci ; 10(2): 93-101, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28296334

RESUMO

We performed a double-blinded, genotype-based stratification study to explore the pharmacokinetics and pharmacodynamics of amitriptyline according to CYP2C19 and CYP2D6 genotype in Korean subjects. Twenty-four healthy adults were grouped by genotype of CYP2C19 and CYP2D6. After a single dose of 25 mg of amitriptyline, blood samples were collected and anticholinergic effects were measured. The extent of N-demethylation of amitriptyline significantly decreased in subjects carrying two nonfunctional alleles of CYP2C19. The extent of hydroxylation of amitriptyline or nortriptyline was significantly reduced in subjects carrying two CYP2D6 decreased functional alleles compared with those with no or one decreased functional allele. The overall metabolic pathway of amitriptyline was more likely to be dominated by CYP2C19 than CYP2D6. The gene variations of CYP2C19 and CYP2D6 did not change the pharmacodynamic effect. The findings of this study will provide useful information on individualized drug treatment with amitriptyline considering both CYP2D6 and CYP2C19 gene variations.


Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Amitriptilina/farmacologia , Antidepressivos Tricíclicos/farmacologia , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Nortriptilina/farmacologia , Polimorfismo Genético , Adulto , Alelos , Povo Asiático/genética , Método Duplo-Cego , Frequência do Gene , Genótipo , Voluntários Saudáveis , Humanos , Masculino , Guias de Prática Clínica como Assunto , República da Coreia , Adulto Jovem
14.
Andrologia ; 49(5)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27401946

RESUMO

This study was performed to examine whether capsaicin, the main pungent ingredient of red peppers, exerts protective effects against testicular injuries induced by transient scrotal hyperthermia. Capsaicin (0.33 mg kg-1 ) was administered subcutaneously to mice one hour before heat stress (HS) in a 43°C water bath for 20 min. After 7 days, mice exposed to HS showed low testicular weight, severe vacuolisation of seminiferous tubules followed by loss of spermatogenic cells, and appearance of multinucleated giant cells and remarkable TUNEL-positive apoptotic cells, as well as weak immunoreactivity of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in spermatogenic cells. Levels of lipid peroxidation and heat shock 70-kDa protein 1 (Hsp72) and BCL2-associated X protein (Bax) mRNA were greatly increased, but PHGPx, manganese superoxide dismutase (MnSOD), and B-cell lymphoma-extra large (Bcl-xL) mRNAs were significantly diminished in the testes by HS. However, capsaicin pre-treatment significantly suppressed the spermatogenic cell death, oxidative stress (levels of MDA, PHGPx immunoreactivity, and Hsp72, PHGPx, and MnSOD mRNA) and apoptosis (levels of TUNEL-positive cells, and Bcl-xL and Bax mRNA) in testes by HS. These suggest that capsaicin has a protective effect against spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities.


Assuntos
Apoptose/efeitos dos fármacos , Capsaicina/administração & dosagem , Temperatura Alta , Escroto/fisiologia , Espermatogênese/fisiologia , Animais , Antioxidantes , Glutationa Peroxidase/análise , Glutationa Peroxidase/genética , Proteínas de Choque Térmico HSP72/genética , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , RNA Mensageiro/análise , Espermatogênese/efeitos dos fármacos , Espermatozoides/citologia , Espermatozoides/enzimologia , Espermatozoides/fisiologia , Superóxido Dismutase/genética , Testículo/química , Testículo/citologia , Testículo/fisiologia , Proteína X Associada a bcl-2/genética
15.
Transplant Proc ; 48(7): 2461-2463, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27742322

RESUMO

The effects of pretransplantation dialysis modality on graft function are key issues in end-stage renal disease patients. The aim of this study was to evaluate post-transplantation outcomes according to pretransplantation renal replacement therapy modality in deceased-donor kidney transplantation. Among 444 deceased-donor kidney transplant recipients in Severance Hospital between April 1993 and Dec 2014, 275 who maintained a unique dialysis modality (hemodialysis [HD; n = 178] or peritoneal dialysis [PD; n = 97]) until transplantation were enrolled. There were no significant differences in sex, age, human leukocyte antigen mismatch, cold ischemic time, or duration of dialysis between groups. There was also no difference in 5-year graft survival between HD and PD groups (87.7% vs. 82.3%, respectively; P = .148). On multivariate Cox regression for risk factors affecting graft survival, renal replacement therapy modality was not found to be a risk factor. However, the rate of delayed graft function was higher in the HD group than in the PD group (32.0% vs. 19.6%, respectively; P = .028). In addition, graft function at 1 week after transplantation in the PD group was superior to that in the HD group. The pretransplantation dialysis modality was found to affect both delayed graft function and early graft function, although not graft survival.


Assuntos
Função Retardada do Enxerto/fisiopatologia , Sobrevivência de Enxerto/fisiologia , Transplante de Rim/mortalidade , Diálise Peritoneal/mortalidade , Diálise Renal/mortalidade , Adulto , Função Retardada do Enxerto/etiologia , Feminino , Humanos , Falência Renal Crônica/terapia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Fatores de Risco , Doadores de Tecidos , Resultado do Tratamento
16.
Transplant Proc ; 48(4): 1270-4, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27320601

RESUMO

BACKGROUND: Thalidomide (TM) is known to have anti-cancer and anti-inflammatory properties; however, its mechanism on T cells is still unclear. We previously showed the immune modulatory effect of TM on T cells and its therapeutic effect on lupus nephritis models. Here we examined the changes in the expression of tumor necrosis factor receptor superfamilies (TNFRSFs), including OX40, 4-1BB, and glucocorticoid-induced TNFR-related protein (GITR) in T cell subsets by TM treatments. METHODS: Splenic naïve T cells (Tnaives) from C57BL/6 mice were sort-purified and cultured for CD4(+) T cell proliferation and regulatory T cells (Tregs) conversion with TM treatments. All samples were analyzed by flow cytometry after stained with anti-mouse CD4, Foxp3, OX40, 4-1BB, or GITR antibodies. RESULTS: Expressions of OX40, 4-1BB, and GITR on CD4(+) T cells showed a decreasing tendency by TM treatments. Especially, downregulation of these molecules on CD4(+)CFSE(low) T cells was significant in TM treatment groups. On the condition of Treg conversion, OX40 was downregulated significantly. In contrast, the expression of GITR was increased, and that of 4-1BB had shown no particular change under the condition of Treg. CONCLUSION: Considering these results, TM may have an immune modulatory role through the T cell subset-specific change of OX40, 4-1BB, and GITR expression. Further study is required to elucidate the effect of thalidomide on T cells.


Assuntos
Ligante 4-1BB/metabolismo , Proteína Relacionada a TNFR Induzida por Glucocorticoide/metabolismo , Imunossupressores/farmacologia , Receptores OX40/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Talidomida/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Receptores do Fator de Necrose Tumoral/metabolismo , Baço/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
17.
Int J Clin Pract ; 70(4): 351-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27028673

RESUMO

OBJECTIVES: The aim of this study was to evaluate the persistence with solifenacin therapy over a 12-month period in patients with overactive bladder (OAB). METHODS: This is a 52-week long, multicenter, prospective, observational study. The subjects were individuals ≥ 18 years old with OAB symptoms for ≥ 3 months, characterised by a total OAB Symptom Score (OABSS) of ≥ 3 and OABSS urgency item score of ≥ 2. Patients were prescribed 5 mg or 10 mg of solifenacin once daily for OAB symptoms. Drug persistence, reasons for discontinuation and factors related to the persistence were evaluated. RESULTS: A total of 1018 patients (329 men, 689 women) with a mean age of 59 years were included. The 52-week drug persistence rate was 22.1%. The drug persistence rates at 12, 24 and 36 weeks were 72.4%, 45.8% and 31.1% respectively. The three most common reasons for discontinuing therapy included symptom improvement in 30.4%, lack of efficacy in 13.4%, and a switch to another antimuscarinic agent in 10.8%. Older patients (odds ratio = 1.02, 95% CI: 1.01-1.04), and female patients (odds ratio = 1.94, 95% CI: 1.37-2.75) were more likely to continue the medication over the 12-month period than were younger, male patients. The number of nocturia episodes was negatively correlated with drug persistence (odds ratio = 0.83, 95% CI: 0.71-0.97). CONCLUSIONS: There was low persistence (22%) to solifenacin therapy for OAB symptoms over a 12-month period. Older patients, female patients and those with fewer episodes of nocturia were more persistent to therapy than were others.


Assuntos
Succinato de Solifenacina/uso terapêutico , Bexiga Urinária Hiperativa/tratamento farmacológico , Urodinâmica/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Bexiga Urinária Hiperativa/fisiopatologia , Agentes Urológicos/uso terapêutico
18.
Am J Transplant ; 16(1): 44-57, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26430779

RESUMO

Apoptosis during engraftment and inflammation induce poor islet xenograft survival. We aimed to determine whether overexpression of human heme oxygenase-1 (HO-1) or soluble tumor necrosis factor-α receptor type I with human IgG1 Fc (sTNF-αR-Fc) in porcine islets could improve islet xenograft survival. Adult porcine islets were transduced with adenovirus containing human HO-1, sTNF-αR-Fc, sTNF-αR-Fc/HO-1 or green fluorescent protein (control). Humanized mice were generated by injecting human cord blood-derived CD34(+) stem cells into NOD-scid-IL-2Rγ(null) mice. Both HO-1 and sTNF-αR-Fc reduced islet apoptosis under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction without compromising insulin secretion. Introduction of either gene into islets prolonged islet xenograft survival in pig-to-humanized mice transplantation. The sTNF-αR-Fc/HO-1 group showed the best glucose tolerance. Target genes were successfully expressed in islet xenografts. Perigraft infiltration of macrophages and T cells was suppressed with decreased expression of RANTES, tumor necrosis factor-α and IL-6 in treatment groups; however, frequency of pig-specific interferon-γ-producing T cells was not decreased, and humoral response was not significant in any group. Early apoptosis of islet cells was suppressed in the treatment groups. In conclusion, overexpression of HO-1 or sTNF-αR-Fc in porcine islets improved islet xenograft survival by suppressing both apoptosis and inflammation. HO-1 or sTNF-αR-Fc transgenic pigs have potential for islet xenotransplantation.


Assuntos
Diabetes Mellitus Experimental/prevenção & controle , Heme Oxigenase-1/genética , Imunoglobulina G/genética , Transplante das Ilhotas Pancreáticas , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Animais , Apoptose , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/cirurgia , Modelos Animais de Doenças , Citometria de Fluxo , Humanos , Ilhotas Pancreáticas/citologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Reação em Cadeia da Polimerase em Tempo Real , Suínos , Transplante Heterólogo
19.
Clin Otolaryngol ; 41(5): 579-84, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26475571

RESUMO

OBJECTIVES: We hypothesised that paediatric chronic sinusitis patients might have various clinical characteristics, depending on age, compared symptoms, physical findings and clinical features in younger children and older adolescent patients who underwent endoscopic sinus surgery. DESIGN: A retrospective review of medical records. SETTING: A total of 195 paediatric patients who underwent Endoscopic sinus surgery were enrolled and medical records were reviewed. PARTICIPANTS: The subjects were divided into children (age < 12 years, n = 70, mean age = 9.6 years) and adolescents (age ≥ 12 years, n = 125, mean age = 14.7 years). MAIN OUTCOME MEASURES: Subjective symptoms, physical findings, CT images and clinical features were compared in children and adolescent groups. RESULTS: Cough and nasal obstruction were more common in adolescents, and sleep disturbance was more common in children. Nasal mucosal injection was more common in adolescents, whereas tonsils were larger in children. Septal deviation was a more common finding in adolescents, and total CT score and serum total IgE levels were higher in children. There was no statistical difference in rate of recurrence after endoscopic sinus surgery. CONCLUSION: The clinical features of paediatric chronic sinusitis differed between the younger and older groups. Symptomatic, anatomical and clinical differences between these two groups suggest that further study of paediatric chronic sinusitis should stratify patients by age to better understand the effects of treatment on each age group.


Assuntos
Endoscopia/métodos , Sinusite/cirurgia , Adolescente , Fatores Etários , Criança , Doença Crônica , Tosse , Feminino , Humanos , Masculino , Obstrução Nasal/cirurgia , Estudos Retrospectivos , Sinusite/diagnóstico por imagem , Tomografia Computadorizada por Raios X
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