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1.
Blood ; 142(4): 352-364, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37146246

RESUMO

Aggressive natural killer cell leukemia (ANKL) is a rare lymphoid neoplasm frequently associated with Epstein-Barr virus, with a disastrously poor prognosis. Owing to the lack of samples from patients with ANKL and relevant murine models, comprehensive investigation of its pathogenesis including the tumor microenvironment (TME) has been hindered. Here we established 3 xenograft mice derived from patients with ANKL (PDXs), which enabled extensive analysis of tumor cells and their TME. ANKL cells primarily engrafted and proliferated in the hepatic sinusoid. Hepatic ANKL cells were characterized by an enriched Myc-pathway and proliferated faster than those in other organs. Interactome analyses and in vivo CRISPR-Cas9 analyses revealed transferrin (Tf)-transferrin receptor 1 (TfR1) axis as a potential molecular interaction between the liver and ANKL. ANKL cells were rather vulnerable to iron deprivation. PPMX-T003, a humanized anti-TfR1 monoclonal antibody, showed remarkable therapeutic efficacy in a preclinical setting using ANKL-PDXs. These findings indicate that the liver, a noncanonical hematopoietic organ in adults, serves as a principal niche for ANKL and the inhibition of the Tf-TfR1 axis is a promising therapeutic strategy for ANKL.


Assuntos
Infecções por Vírus Epstein-Barr , Leucemia Linfocítica Granular Grande , Leucemia Prolinfocítica de Células T , Animais , Humanos , Camundongos , Proliferação de Células , Infecções por Vírus Epstein-Barr/patologia , Herpesvirus Humano 4 , Leucemia Linfocítica Granular Grande/patologia , Fígado/patologia , Transferrinas , Microambiente Tumoral
2.
J Infect Chemother ; 29(1): 26-32, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36100144

RESUMO

BACKGROUND: Several carbapenemases have been identified globally in Enterobacteriaceae. In Japan, IMP-type carbapenemase is the most prevalent, although cases of carbapenemase-producing Enterobacteriaceae (CPE) bacteremia are still scarce. The present case series and literature review aimed to elucidate the clinical characteristics and treatment strategies for IMP-type CPE bacteremia. METHODS: Clinical data on pediatric cases of IMP-type CPE bacteremia at the Tokyo Metropolitan Children's Medical Center between 2010 and 2020 were collected, and a review of past studies of IMP-type CPE bacteremia has been provided. RESULTS: Five pediatric episodes of IMP-type CPE bacteremia were identified. Our review of previous literature on IMP-type CPE bacteremia revealed 24 adult patients, but no pediatric patients. All 29 cases had underlying diseases, and 23 (79%) received combination therapy. The median duration of antibiotic therapy was 14 days (interquartile range: 9-14 days). The overall mortality rate was 38% (11/29). The mortality rates associated with monotherapy and combination therapy were 67% (4/6) and 30% (7/23), respectively. CONCLUSIONS: We report the first case series of IMP-type CPE bacteremia in children. Our review of past studies suggests that combination therapy might lead to better survival outcomes in patients with IMP-type CPE bacteremia. Further research is needed to establish an optimal treatment strategy for IMP-type CPE bacteremia.


Assuntos
Bacteriemia , Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Enterobacteriaceae , Adulto , Criança , Humanos , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Proteínas de Bactérias , beta-Lactamases , Enterobacteriaceae , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/tratamento farmacológico , Testes de Sensibilidade Microbiana
3.
FASEB J ; 35(4): e21505, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33723887

RESUMO

Epstein-Barr virus (EBV) causes malignant carcinomas including B cell lymphomas accompanied by the systemic inflammation. Previously, we observed that phosphatidylserine (PS)-exposing subset of extracellular vesicles (EVs) secreted from an EBV strain Akata-transformed lymphoma (Akata EVs) convert surrounding phagocytes into tumor-associated macrophages (TAMs) via induction of inflammatory response, which is in part mediated by EBV-derived micro RNAs. However, it is still unclear about EV-carried other potential inflammatory factors associated with TAM formation in EBV lymphomas. To this end, we sought to explore proteomic and phospholipidomic profiles of PS-exposing EVs derived from EBV-transformed lymphomas. Mass spectrometric analysis revealed that several immunomodulatory proteins including integrin αLß2 and fibroblast growth factor 2 (FGF2) were highly expressed in PS-exposing Akata EVs compared with another EBV strain B95-8-transformed lymphoma-derived counterparts which significantly lack TAM-inducing ability. Pharmacological inhibition of either integrin αLß2 or FGF2 hampered cytokine induction in monocytic cultured cells elicited by PS-exposing Akata EVs, suggesting the involvement of these proteins in EV-mediated TAM induction in EBV lymphomas. In addition, phospholipids containing precursors of immunomodulatory lipid mediators were also enriched in PS-exposing Akata EVs compared with B95-8 counterparts. Phospholipidomic analysis of fractionated Akata EVs by density gradient centrifugation further demonstrated that PS-exposing Akata EVs might be identical to certain Akata EVs in low density fractions containing exosomes. Therefore, we concluded that a variety of immunomodulatory cargo molecules in a certain EV subtype are presumably conducive to the development of EBV lymphomas.


Assuntos
Infecções por Vírus Epstein-Barr/metabolismo , Vesículas Extracelulares/metabolismo , Linfoma/virologia , Microambiente Tumoral/fisiologia , Proliferação de Células/fisiologia , Infecções por Vírus Epstein-Barr/virologia , Exossomos/metabolismo , Exossomos/virologia , Herpesvirus Humano 4/patogenicidade , Herpesvirus Humano 4/fisiologia , Humanos , Linfoma/metabolismo
4.
Blood ; 131(23): 2552-2567, 2018 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-29685921

RESUMO

Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBV-encoded RNA. We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-α, and arginase 1, suggesting the immune regulatory role of BART miRNAs. The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma. These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV+ B-cell lymphoma.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Exossomos/virologia , Herpesvirus Humano 4/genética , Inflamação/virologia , Linfoma/virologia , RNA Viral/genética , Animais , Carcinogênese/genética , Carcinogênese/imunologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Exossomos/genética , Exossomos/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/isolamento & purificação , Humanos , Inflamação/etiologia , Inflamação/genética , Inflamação/imunologia , Linfoma/etiologia , Linfoma/genética , Linfoma/imunologia , Camundongos , MicroRNAs/análise , MicroRNAs/genética , RNA Viral/análise , Análise de Sequência de RNA , Microambiente Tumoral
5.
J Infect Chemother ; 26(5): 510-512, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31982291

RESUMO

Eikenella corrodens is a facultatively anaerobic gram-negative rod bacterium in the oropharynx and respiratory tract. It is a member of HACEK (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, E. corrodens, and Kingella kingae) group commonly associated with endocarditis and craniofacial infections. It is usually susceptible to penicillin, second and third-generation cephalosporins, and carbapenem, but has variable susceptibility to first-generation cephalosporin. We herein provide a description of the first case of pediatric acute dacryocystitis caused by E. corrodens. The patient did not respond to oral cephalexin and required surgical drainage followed by intravenous cefotaxime. Also provided is a brief review of the current literature.


Assuntos
Dacriocistite/diagnóstico , Dacriocistite/microbiologia , Eikenella corrodens/patogenicidade , Infecções por Bactérias Gram-Negativas/microbiologia , Doença Aguda , Aggregatibacter , Antibacterianos/administração & dosagem , Cardiobacterium , Cefotaxima/administração & dosagem , Cefalexina/administração & dosagem , Pré-Escolar , Dacriocistite/tratamento farmacológico , Vias de Administração de Medicamentos , Eikenella corrodens/isolamento & purificação , Feminino , Infecções por Bactérias Gram-Negativas/diagnóstico , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Haemophilus , Humanos , Kingella , Testes de Sensibilidade Microbiana , Tomografia Computadorizada por Raios X , Resultado do Tratamento
6.
J Orthop Sci ; 25(1): 167-172, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30904204

RESUMO

BACKGROUND: Hand-grip strength was reported to be important predictor of functional limitation and disability related to low muscle strength in old people. The purpose of this study was to determine whether preoperative hand-grip strength predicts stair ascent and descent ability after total knee arthroplasty (TKA). METHODS: A total of 83 female patients (mean age 75.6 ± 7.2 years) who underwent unilateral TKA were included in this study. We measured body mass index, range of motion of both knees, bilateral quadriceps strength and hand-grip strength before and one year after TKA. One year after TKA, we had the subjects ascend and descend some stairs and recorded the gait pattern (step-to-step or step-over-step) and pain in both knees using a numerical rating scale. We divided the subjects into two groups according to gait pattern. These factors were compared between groups. Receiver Operating Characteristics (ROC) analysis was performed to estimate the preoperative hand-grip strength cut off point for the stair gait pattern. RESULTS: Pre- and postoperative mean hand-grip strengths were 20.1 ± 5.0 kg and 20.7 ± 5.4 kg, respectively, and there was a strong positive correlation between them (r = 0.82, P < 0.001). Quadriceps strength of both limbs significantly improved after TKA (P < 0.001). After TKA, all patients were able to perform both stair ascent and descent. The gait patterns of 27 patients were step-to-step, and 56 patients were step-over-step. Preoperative and postoperative quadriceps strength of both limbs and preoperative and postoperative hand-grip strength were significantly different between the groups. According to the ROC curve, the optimal cut off values of preoperative hand-grip strength for which female patients could ascend and descend the stairs by step-over-step after TKA was set at 19 kg. CONCLUSION: Preoperative hand-grip strength can be used in preoperative screening for stair ascent and descent ability after TKA.


Assuntos
Artroplastia do Joelho , Marcha , Força da Mão , Osteoartrite do Joelho/cirurgia , Músculo Quadríceps/fisiopatologia , Subida de Escada , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Medição da Dor , Período Pré-Operatório , Curva ROC
7.
Immunology ; 158(4): 340-352, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31520477

RESUMO

Siglecs are cell surface lectins that recognize sialic acids and are primarily expressed in hematopoietic cells. Previous studies showed that some Siglecs regulate macrophage function. In the present study, we examined the induction and putative roles of mouse Siglec-F in bone-marrow-derived macrophages in mice. A quantitative RT-PCR analysis showed that the basal expression of Siglec-F was weak in bone-marrow-derived macrophages differentiated by macrophage colony-stimulating factor. However, a 24-hr stimulation with granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced Siglec-F expression. GM-CSF also enhanced Siglec-F expression in thioglycollate-induced peritoneal macrophages. The inhibition of signal transducer and activator of transcription 5 (STAT5), but not that of phosphoinositide 3-kinase or mitogen-activated protein kinase kinase, significantly reduced the induction of Siglec-F. Interleukin-3, which uses a common ß-chain shared with the GM-CSF receptor to stimulate the STAT5 pathway, also enhanced Siglec-F expression. The knockdown of Siglec-F by a specific small interfering RNA enhanced GM-CSF-induced STAT5 phosphorylation, suggesting that Siglec-F down-regulates its own expression upon prolonged GM-CSF stimulation. Furthermore, the knockdown of Siglec-F reduced the STAT6 phosphorylation and expression of arginase-1 in interleukin-4-stimulated macrophages. These results suggest that Siglec-F fine-tunes the immune responses of macrophages.


Assuntos
Antígenos de Diferenciação Mielomonocítica/metabolismo , Arginase/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Interleucina-4/metabolismo , Macrófagos/imunologia , Animais , Antígenos de Diferenciação Mielomonocítica/genética , Arginase/genética , Células Cultivadas , Interleucina-4/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação , RNA Interferente Pequeno/genética , Fator de Transcrição STAT5/metabolismo , Fator de Transcrição STAT6/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico , Regulação para Cima
8.
Pediatr Int ; 61(6): 572-577, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30908807

RESUMO

BACKGROUND: Pyelonephritis caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is an urgent problem in pediatrics. Although carbapenem is the standard therapy for infections caused by ESBL-producing Enterobacteriaceae, some cephamycins, including cefmetazole, are stable against hydrolysis by ESBL. There are few reports, however, on the use of cefmetazole in children. The aim of this study was to evaluate the therapeutic effect of cefmetazole in pediatric pyelonephritis caused by ESBL-producing Enterobacteriaceae. METHODS: Children with pyelonephritis caused by ESBL-producing Enterobacteriaceae were enrolled between April 2010 and November 2016 at Tokyo Metropolitan Children's Medical Center. Presence of ESBL was tested for using the disk diffusion method. Medical records were reviewed for a past history of bacterial infection. The outcomes were clinical cure rate at 4 weeks and the duration of therapy in the cefmetazole and non-cefmetazole groups. RESULTS: Fifty-five patients met the criteria for pyelonephritis caused by ESBL-producing Enterobacteriaceae. The most common causative organisms were Escherichia coli (n = 51; 92.7%), Klebsiella pneumoniae (n = 3; 5.5%), and K. oxytoca (n = 1; 1.8%). Thirty-six and 19 patients were treated with cefmetazole and with other antibiotics as definitive therapy, respectively. There was no difference in the clinical cure rate (86.1% vs 89.5%; P = 0.72) or duration of therapy (median, 7.0 vs 7.0 days; P = 0.73) between the cefmetazole and non-cefmetazole groups. CONCLUSIONS: Cefmetazole was not inferior to the other antibiotics in the treatment of pyelonephritis caused by ESBL-producing Enterobacteriaceae in children. Cefmetazole is a valuable therapeutic alternative to carbapenems for treating pyelonephritis caused by ESBL-producing Enterobacteriaceae.


Assuntos
Antibacterianos/uso terapêutico , Cefmetazol/uso terapêutico , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/enzimologia , Pielonefrite/tratamento farmacológico , beta-Lactamases/metabolismo , Adolescente , Biomarcadores/metabolismo , Criança , Pré-Escolar , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/diagnóstico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Lactente , Masculino , Pielonefrite/diagnóstico , Pielonefrite/microbiologia , Estudos Retrospectivos , Resultado do Tratamento
9.
Rinsho Ketsueki ; 60(9): 1070-1074, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597829

RESUMO

The secretion of extracellular vesicles (EVs) from cells has been observed. Recently, because EVs were found to contain functional molecules such as micro RNAs (miRNAs) and possess the ability to transfer them to other cells, its functions were expanded as an "intracellular communicator." The exosome is one such EV that has been extensively investigated, particularly in cancer research because cancer cells abundantly secrete exosomes, suggesting their potential as promising diagnostic markers. Research on exosomes in the hematopoietic system has just begun. We recently reported that the exosome secreted from the EBV-infected lymphoma cells has critical functions in lymphomagenesis and maintenance. Moreover, EVs in HBV infection are now being investigated to generalize their functions.


Assuntos
Exossomos/fisiologia , Sistema Hematopoético/fisiologia , Hepatite B , Humanos , Linfoma , MicroRNAs
10.
Pediatr Int ; 60(2): 153-156, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29205682

RESUMO

BACKGROUND: Sibling visits to the neonatal intensive care unit (NICU) are a part of family-centered care, which is now being increasingly endorsed as a positive development in patient care. Sibling visits, however, pose a risk of viral infection, and hence many NICU in Japan impose strict limits on the practice. The aim of this study was therefore to assess whether sibling visits to the NICU are related to an increase in the nosocomial viral infection rate. METHODS: This retrospective study was conducted between April 2012 and March 2017 at Tokyo Metropolitan Children's Medical Center in Japan. Sibling visits were implemented after screening for symptoms of viral illness. Symptomatic patients in the NICU were tested for common viruses on rapid antigen test and polymerase chain reaction. The number of sibling visits and the rate of nosocomial viral infections were examined on Spearman's correlation test. RESULTS: The total number of sibling visits and rate of nosocomial viral infection in the NICU was 102 and 0.068 per 1,000 patient-days during the study period, respectively. The number of enterovirus, respiratory syncytial virus, human metapneumovirus, influenza virus A, and Herpes simplex virus infections was 3, 2, 1, 1, 1, and 1, respectively. No infections were identified after sibling visits. The number of sibling visits and the rate of nosocomial viral infections were not correlated (correlation coefficient, -0.1; P = 0.873). CONCLUSION: Sibling visits to the NICU did not result in an increase in the nosocomial viral infection rate.


Assuntos
Infecção Hospitalar/epidemiologia , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Viroses/epidemiologia , Visitas a Pacientes/estatística & dados numéricos , Pré-Escolar , Infecção Hospitalar/etiologia , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Estudos Retrospectivos , Irmãos , Viroses/etiologia
11.
Arthroscopy ; 34(5): 1631-1637, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29456068

RESUMO

PURPOSE: To prospectively evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) for diagnosing ramp lesions, to compare them between 1.5- and 3-T MRI, and to evaluate whether bone contusion of the posterior lip of the medial tibial plateau was associated with ramp lesions. METHODS: For 155 knees that underwent primary ACL reconstruction, we prospectively examined for ramp lesions and medial meniscal body tears on MRI. MRI diagnosis of ramp lesions required high signal irregularity of the capsular margin or separation in the meniscocapsular junction of the medial meniscus posterior horn on sagittal images. Bone contusion of the posterior lip of the medial tibial plateau was verified in 105 knees with MRI performed within 6 weeks after injury. All ramp lesions were identified by transcondylar observation during surgery. The sensitivity and specificity of MRI for ramp lesions and body tears were measured. Furthermore, we evaluated whether bone contusion of the medial tibial plateau was associated with ramp lesions. The χ-square test was used for statistical analysis. RESULTS: During surgery, ramp lesions were observed in 46 knees and medial meniscal body tears were seen in 35 knees. The sensitivity of MRI for ramp lesions was 71.7% and specificity was 90.5%. The sensitivity for ramp lesions was significantly lower than that for meniscal body tears (94.3%) (P = .01). The sensitivity of 3-T MRI (83.3%) was superior to that of 1.5-T MRI (67.6%), but not significantly different. The incidence of bone contusions was not significantly different among ramp lesions (38.5%), body tears (40.0%), or no tears (30.5%). CONCLUSIONS: The sensitivity of MRI for diagnosing ramp lesions was significantly lower than that for medial meniscal body tears. Bone contusion of the posterior lip of the medial tibial plateau on MRI was not associated with ramp lesions. LEVEL OF EVIDENCE: Level III, comparative trial.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Imageamento por Ressonância Magnética/métodos , Meniscos Tibiais/diagnóstico por imagem , Lesões do Menisco Tibial/diagnóstico , Adolescente , Adulto , Lesões do Ligamento Cruzado Anterior/complicações , Lesões do Ligamento Cruzado Anterior/diagnóstico , Feminino , Humanos , Masculino , Meniscos Tibiais/cirurgia , Pessoa de Meia-Idade , Estudos Prospectivos , Lesões do Menisco Tibial/etiologia , Lesões do Menisco Tibial/cirurgia , Adulto Jovem
12.
J Arthroplasty ; 33(5): 1389-1393, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29352685

RESUMO

BACKGROUND: The purpose of our study was to identify factors affecting posterior cruciate ligament (PCL) tightness during cruciate-retaining total knee arthroplasty. METHODS: A total of 225 varus osteoarthritic knees that underwent cruciate-retaining total knee arthroplasty were included in this study. When the flexion gap was tighter than the extension gap after all bone resection and the lift-off sign was positive during surgery, the PCL was released. The association between PCL release and potential risk factors, such as age, gender, body mass index, preoperative range of motion, anterior cruciate ligament status, preoperative hip-knee-ankle angle (HKA), decrease in posterior condylar offset, and also change in tibial posterior slope angle (TPSA) from preoperative to postoperative measurement, was evaluated by univariate and multivariate logistic regression analyses. RESULTS: The PCL was released in 68 of 225 knees (30.2%). According to the univariate logistic regression analysis, preoperative knee flexion angle (odds ratio [OR], 0.98), anterior cruciate ligament status (OR, 3.94), the decrease in medial (OR, 0.73) and lateral posterior condylar offset (OR, 0.76), preoperative HKA (OR, 1.1), preoperative (OR, 1.15) and postoperative TPSA (OR, 0.77), and the decrease in TPSA (OR, 1.23) were associated with PCL release. Multivariable stepwise logistic regression analysis demonstrated that preoperative HKA (P < .001), postoperative TPSA (P = .02), and the decrease in TPSA (P < .001) were independently associated with PCL release. CONCLUSION: Many factors are associated with PCL tightness. The change in TPSA between preoperative and postoperative measurements was a higher risk factor than postoperative TPSA.


Assuntos
Artroplastia do Joelho , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Ligamento Cruzado Posterior/cirurgia , Idoso , Idoso de 80 Anos ou mais , Ligamento Cruzado Anterior/cirurgia , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Variações Dependentes do Observador , Razão de Chances , Período Pós-Operatório , Amplitude de Movimento Articular , Tíbia/cirurgia
13.
J Arthroplasty ; 32(6): 1808-1813, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28185754

RESUMO

BACKGROUND: The purpose of this study is to investigate whether varus-valgus laxity of cruciate-retaining (CR) total knee arthroplasty (TKA) changes between 1 year and >5 years after surgery based on postoperative limb alignment. METHODS: One hundred twenty-one varus osteoarthritic knees that underwent CR TKA were included. The minimum follow-up was 5 years. Weight-bearing full-leg radiographs were obtained postoperatively and the hip-knee-ankle (HKA) angle was measured. Knees were grouped in varus (HKA angle ≤ -3°, 47 knees) and neutral groups (-3° < HKA angle < 3°, 70 knees). The range of motion was measured and a Hospital for Special Surgery score was obtained at the last follow-up. Varus-valgus laxity at 15° of knee flexion was measured with stress radiographs after 1 year and at the last follow-up. RESULTS: No knees required revision surgery. The mean knee flexion angle (121.0° vs 117.1°) and Hospital for Special Surgery score (90.3 vs 90.4) at the last follow-up were not significantly different between the varus and neutral groups. In both groups, there was no significant change in varus or valgus laxity between 1 year and at the last follow-up. CONCLUSION: Postoperative residual varus limb alignment did not lead to increasing varus laxity after CR TKA in the mid-term.


Assuntos
Artroplastia do Joelho/efeitos adversos , Instabilidade Articular/etiologia , Articulação do Joelho/fisiologia , Idoso , Idoso de 80 Anos ou mais , Articulação do Tornozelo/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Instabilidade Articular/fisiopatologia , Joelho/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Radiografia , Amplitude de Movimento Articular , Suporte de Carga
14.
Biosci Biotechnol Biochem ; 80(6): 1141-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26923638

RESUMO

Siglecs recognize the sialic acid moiety and regulate various immune responses. In the present study, we compared the expression levels of Siglecs in human monocytes and macrophages using a quantitative real-time reverse transcription-polymerase chain reaction analysis. The differentiation of monocytes into macrophages by macrophage colony-stimulating factor or granulocyte macrophage colony-stimulating factor enhanced the expression of Siglec-7 and Siglec-9. The differentiated macrophages were stimulated by lipopolysaccharide (LPS) plus interferon (IFN)-γ or interleukin (IL)-4. The expression of Siglec-10 was enhanced by IL-4, whereas that of Siglec-7 was reduced by LPS plus IFN-γ. The expression of Siglec-9 was not affected by these stimuli. The knockdown of Siglec-9 enhanced the expression of CCR7 induced by the LPS or the LPS plus IFN-γ stimulation, and decreased the IL-4-induced expression of CD200R. These results suggest that Siglec-9 is one of the main Siglecs in human blood monocytes/macrophages and modulates innate immunity.


Assuntos
Antígenos CD/imunologia , Antígenos de Superfície/imunologia , Macrófagos/imunologia , Receptores CCR7/imunologia , Receptores de Superfície Celular/imunologia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/imunologia , Antígenos CD/genética , Antígenos de Superfície/genética , Diferenciação Celular , Regulação da Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Imunidade Inata , Interferon gama/farmacologia , Interleucina-4/farmacologia , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Fator Estimulador de Colônias de Macrófagos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Receptores de Orexina , Cultura Primária de Células , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Receptores CCR7/genética , Receptores de Superfície Celular/genética , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/antagonistas & inibidores , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , Transdução de Sinais
15.
Biosci Biotechnol Biochem ; 80(3): 501-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26540411

RESUMO

Siglecs, an immunoglobulin-like lectin family that recognizes the sialic acid moiety, regulate various aspects of immune responses. In the present study, we investigated the effects of Siglecs on the macrophage cell line RAW264, which was stimulated with interleukin-4 (IL-4). The induction of arginase-1 (Arg1) by IL-4 was stronger in Siglec-9-expressing cells than in mock cells. Mutations in the cytoplasmic tyrosine-based inhibitory motifs in Siglec-9 markedly reduced the expression of Arg1. The phosphorylation of Akt by IL-4 and extracellular signal-regulated kinase (ERK) without IL-4 was stronger in Siglec-9-expressing cells, indicating the enhanced activation of the phosphatidylinositol 3 kinase (PI-3K) and mitogen-activated protein kinase kinase (MEK)/ERK pathways, respectively. The enhanced expression of Arg1 was inhibited by MEK inhibitors, but not by PI-3K inhibitor. These results indicate that Siglec-9 affects several different signaling pathways in IL-4-stimulated macrophages, which resulted in enhanced induction of Arg1 in Siglec-9-expressing RAW264 cells.


Assuntos
Interleucina-4/fisiologia , Macrófagos/imunologia , Animais , Antígenos CD , Antígenos de Diferenciação de Linfócitos B , Arginase/metabolismo , Linhagem Celular , Células Cultivadas , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Fator de Transcrição STAT6/metabolismo
16.
J Infect Chemother ; 22(8): 532-5, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27263807

RESUMO

BACKGROUND: The spread of antimicrobial-resistant organisms is a global concern. To stem this tide, an antimicrobial stewardship program at hospitals is essential to optimize the prescription of broad spectrum antibiotics. In this study we examined the impact of computerized pre-authorization for broad spectrum antibiotics for Pseudomonas aeruginosa at a children's hospital. METHODS: An antimicrobial stewardship program at Tokyo Metropolitan Children's Medical Center was assessed between March 2010 and March 2015. A paper-based post-prescription audit was switched to computerized pre-authorization for broad antipseudomonal agents in October 2011. The prescriber was required to obtain approval from physicians in the pediatric infectious diseases division before prescribing restricted antimicrobial agents. Approved prescriptions were processed and logged electronically. We evaluated days of therapy per 1000 patient-days, the cost of antibiotics, and the susceptibility of P. aeruginosa to piperacillin, ceftazidime, cefepime, piperacillin/tazobactam, carbapenems, and ciprofloxacin. Also, the average length of admission and infection-related mortality at 30 days were compared pre- and post-intervention. RESULTS: Administration of carbapenems, piperacillin/tazobactam, and ceftazidime decreased significantly after the introduction of computerized pre-authorization. Antibiotic costs were reduced by JPY2.86 million (USD 26,000) annually. None of the antipseudomonal agents showed decreased sensitivity. The average length of admission was shorter in post-intervention. Infection-related mortality at 30 days showed no difference between the pre- and post-intervention periods. CONCLUSION: An antimicrobial stewardship program using computerized pre-authorization decreased the use and cost of broad spectrum antibiotics without significant difference in infection-related mortality at 30 days, although our study did not improve susceptibilities of P. aeruginosa.


Assuntos
Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Carbapenêmicos/uso terapêutico , Cefepima , Ceftazidima/uso terapêutico , Cefalosporinas/uso terapêutico , Hospitais , Humanos , Japão , Testes de Sensibilidade Microbiana , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Tóquio
17.
J Arthroplasty ; 31(10): 2303-7, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27155995

RESUMO

BACKGROUND: The tibial tubercle (TT) is the most reliable landmark of the tibial component rotation in total knee arthroplasty. However, there is no report comparing the position of the TT between valgus and varus osteoarthritic knees. METHODS: Using preoperative computed tomography, we measured the TT-posterior cruciate ligament (PCL) distance representing the degree of lateralization of the TT and the angle between Akagi's anteroposterior (AP) axis and the dorsal condylar line (DCL) of the tibia in 36 valgus and 40 varus osteoarthritic knees and compared them. RESULTS: The mean TT-PCL distances in valgus and varus knees were 26.1 (18.2-36.8) and 17.2 mm (10.3-22.6), respectively, with a significant difference (P < .001). Twenty-four of 36 valgus knees (67%) had abnormal TT-PCL (>24 mm). The mean AP-DCL angles in valgus and varus knees were 103° (95.8°-114.8°) and 93.2° (85.3°-99.6°), respectively, with a significant difference (P < .001). CONCLUSION: The TT in valgus knees was significantly more laterally positioned than in varus knees. Also, Akagi's AP axis in valgus knees was significantly more externally rotated relative to the DCL of the tibia than in varus knees. Attention is necessary to correct rotational alignment without posterolateral overhang of the tibial component during total knee arthroplasty, particularly for valgus knees.


Assuntos
Osteoartrite do Joelho/patologia , Tíbia/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Ligamento Cruzado Posterior/diagnóstico por imagem , Estudos Retrospectivos , Rotação , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Tomografia Computadorizada por Raios X
18.
Opt Express ; 23(11): A594-603, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26072884

RESUMO

We propose a thin and compact concentrator photovoltaic (CPV) module, about 20 mm thick, one tenth thinner than those of conventional CPVs that are widely deployed for mega-solar systems, to broaden CPV application scenarios. We achieved an energy conversion efficiency of 37.1% at a module temperature of 25 °C under sunlight irradiation optimized for our module. Our CPV module has a lens array consisting of 10 mm-square unit lenses and micro solar cells that are directly attached to the lens array, to reduce the focal length of the concentrator and to reduce optical losses due to reflection. The optical loss of the lens in our module is about 9.0%, which is lower than that of conventional CPV modules with secondary optics. This low optical loss enables our CPV module to achieve a high energy conversion efficiency.

19.
Arthroscopy ; 31(7): 1310-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25801047

RESUMO

PURPOSE: The aim of this study was to compare postoperative outcomes after anatomic double-bundle anterior cruciate ligament reconstruction (ACLR) in extreme knee hyperextension versus normal to mild knee hyperextension. METHODS: For 100 patients who underwent anatomic double-bundle ACLR using semitendinosus tendon, we evaluated the side-to-side difference (SSD) in anterior tibial translation (measured on stress radiographs) and rotational stability (assessed by the pivot-shift test) 2 years after surgery. Loss of extension (LOE) was evaluated on lateral radiographs of both knees in full extension, and graft integrity was assessed during second-look arthroscopy 1 to 2 years after surgery. In accordance with the Beighton and Honan criteria, patients with an extension angle less than or equal to 10° in the contralateral uninjured knee composed the group with 10° or less hyperextension (N group), and those with an extension angle of greater than 10° composed the group with more than 10° hyperextension (H group). Postoperative results were compared between these groups. RESULTS: Mean extension angles in the N and H groups were 5.8° ± 2.9° and 14.7° ± 3.0°, respectively. The mean SSD in anterior translation was 2.2 ± 2.9 mm for the N group and 2.8 ± 2.9 mm for the H group, with no significant difference. The positive ratios on the pivot-shift test were not significantly different between the groups. Mean LOE in the N and H groups was -0.7° ± 3.7° and 1.3° ± 3.3°, respectively, with a significant difference (P = .007). During second-look arthroscopy, 6 of 58 knees in the N group and 13 of 42 knees in the H group had superficial graft laceration of the anteromedial bundle graft, with a significant difference (P = .01) seen between groups. CONCLUSIONS: Anatomic double-bundle ACLR for extreme knee hyperextension may attain the same postoperative anterior and rotational stability as seen in knees with normal to mild hyperextension. However, it increased superficial graft laceration. LEVEL OF EVIDENCE: Level III, retrospective comparative study.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/cirurgia , Joelho/fisiologia , Adolescente , Adulto , Lesões do Ligamento Cruzado Anterior , Artroscopia/métodos , Feminino , Humanos , Joelho/fisiopatologia , Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Cirurgia de Second-Look , Tendões/transplante , Coxa da Perna/cirurgia , Tíbia/fisiologia , Resultado do Tratamento , Adulto Jovem
20.
Sci Rep ; 14(1): 8808, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627428

RESUMO

Fluoride glasses in the binary system ZrF4-BaF2 were prepared via mechanochemical treatment. The glass-forming region of the ZrF4-BaF2 system obtained using the mechanochemical method was wider than that obtained using the conventional melt-quenching method. The glass-ceramic 60ZrF4·40BaF2 (mol%) sample was obtained by heat treatment and shows a higher conductivity of 1.2 × 10-6 S cm-1 at 200 °C than the pristine glass. This study revealed that mechanochemical treatment was effective for the synthesis of fluoride glasses.

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