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The Gram-negative bacterium A. salmonicida is the causal agent of furunculosis and used to be one of the most loss-causing bacterial infections in the salmonid aquaculture industry with a mortality rate of about 90% until the 1990s, when an inactivated vaccine with mineral oil as adjuvant was successfully implemented to control the disease. However, the use of this vaccine is associated with inflammatory side effects in the peritoneal cavity as well as autoimmune reactions in Atlantic salmon, and incomplete protection has been reported in rainbow trout. We here aimed at developing and testing a recombinant alternative vaccine based on virus-like particles (VLPs) decorated with VapA, the key structural surface protein in the outer A-layer of A. salmonicida. The VLP carrier was based on either the capsid protein of a fish nodavirus, namely red grouper nervous necrotic virus (RGNNV) or the capsid protein of Acinetobacter phage AP205. The VapA and capsid proteins were expressed individually in E. coli and VapA was fused to auto-assembled VLPs using the SpyTag/SpyCatcher technology. Rainbow trout were vaccinated/immunized with the VapA-VLP vaccines by intraperitoneal injection and were challenged with A. salmonicida 7 weeks later. The VLP vaccines provided protection comparable to that of a bacterin-based vaccine and antibody response analysis demonstrated that vaccinated fish mounted a strong VapA-specific antibody response. To our knowledge, this is the first demonstration of the potential use of antigen-decorated VLPs for vaccination against a bacterial disease in salmonids.
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Aeromonas salmonicida , Oncorhynchus mykiss , Animais , Proteínas do Capsídeo/genética , Escherichia coli , Vacinação , Vacinas SintéticasRESUMO
Virus-like particle (VLP)-based vaccines are promising candidates for overcoming the safety problems of live vaccines and weak immunogenicity of subunit vaccines. VLPs can be used as a platform for the development of combined vaccines by expressing foreign antigens, and foreign antigens can be displayed on the surface of VLPs by conjugation. In the present study, to use nervous necrosis virus (NNV) VLPs as a delivery tool for Streptococcus iniae α-enolase by displaying on the VLP's surface, the split-intein (SpyTag/SpyCatcher) conjugation system was used. NNV capsid protein fused to SpyTag (Capsid-SpyTag) and S. iniae α-enolase fused to SpyCatcher (α-enolase-SpyCatcher) were recombinantly produced, then mixed in various ratios. A ratio of Capsid-SpyTag to α-enolase-SpyCatcher of 1 to 1.5 showed the highest coupling efficiency corresponding to 83-92% of coupled capsid protein dimer and 32-52% of coupled capsid protein monomer. In TEM observation, VLP of Capsid-SpyTag had a regular shape and size of about 40 nm, while VLP fused with α-enolase-SpyCatcher showed an irregular shape and size of about 40-50 nm in diameter. In preliminary immunization experiments, olive flounder (Paralichthys olivaceus) and zebrafish (Danio rerio) immunized with VLP fused with α-enolase-SpyCatcher showed the lowest cumulative mortality against S. iniae infection.
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Proteínas do Capsídeo , Streptococcus iniae , Animais , Peixe-Zebra , Fosfopiruvato Hidratase/genética , NecroseRESUMO
Autoreactive B cells are not entirely deleted, but some remain as immunocompetent or anergic B cells. Although the persistence of autoreactive B cells as anergic cells has been shown in transgenic mouse models with the expression of B cell receptor (BCR) reactive to engineered self-antigen, the characterization of naturally occurring anergic B cells is important to identify them and understand their contribution to immune regulation or autoimmune diseases. We report here that a low-level expression of CD138 in the splenic B cells marks naturally arising anergic B cells, not plasma cells. The CD138int B cells consisted of IgMlowIgDhigh follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138int FO B cells showed an anergic gene expression profile shared with that of monoclonal anergic B cells expressing engineered BCRs and the gene expression profile was different from those of plasma cells, age-associated B cells, or germinal center B cells. The anergic state of the CD138int FO B cells was confirmed by attenuated Ca2+ response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or anti-IgG. The BCR repertoire of the CD138int FO B cells was distinct from that of the CD138- FO B cells and included some class-switched B cells with low-level somatic mutations. These findings demonstrate the presence of polyclonal anergic B cells in the normal mice that are characterized by low-level expression of CD138, IgM downregulation, reduced Ca2+ and CD69 responses upon BCR engagement, and distinct BCR repertoire.
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OBJECTIVES: To assess the risk of a fetus with a smaller or larger than expected crown-rump length (CRL) for adverse pregnancy outcomes. METHODS: The data of 960 healthy singleton pregnancies conceived via in vitro fertilization were retrospectively collected. Fetal CRL was measured between 11 and 13 + 6 weeks of gestation, and small and large fetal CRLs were defined as fetuses below the 10th and above the 90th centiles, respectively. Multiple logistic regression analysis was performed to assess the risk for adverse pregnancy outcomes. RESULTS: The mean birth weights of fetuses with small, normal, and large CRLs were 3002 g, 3205 g, and 3378 g, respectively. A small fetal CRL was associated with an increased risk of smaller-than-gestational-age neonates (adjusted odds ratio [aOR], 2.79; 95% confidence interval [CI], 1.53-5.08; P < .001) and preterm delivery before 34 gestational weeks (aOR, 6.48; 95% CI, 1.36-30.79; P = .019). A large fetal CRL was associated with an increased risk of large-for-gestational-age (LGA) neonates, and the risk persisted even after adjustment for well-known risk factors of macrosomia, such as pre-pregnancy body mass index, gestational diabetes, and excessive gestational weight gain (aOR, 3.67; 95% CI, 2.04-6.59; P < .001). However, a large fetal CRL was associated with a decreased risk of gestational diabetes (aOR, 0.10; 95% CI, 0.01-0.76; P = .026). CONCLUSIONS: Fetal CRL measured at 11 to 13 + 6 weeks gestation is worth using as a predictor of LGA as well as small for gestational age or preterm delivery.
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Diabetes Gestacional , Nascimento Prematuro , Estatura Cabeça-Cóccix , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-Natal/efeitos adversosRESUMO
The polymerization of monomeric antigens can be a strategy to overcome the low immunogenicity of subunit vaccines. IMX313 is a hybrid oligomerization domain of chicken C4bp, and has been demonstrated to have potent activity as adjuvants for the fused antigens in mammals. In the present study, we investigated whether the oligomerization of α-enolase of Streptococcus iniae by fusion with IMX313 affected on antibody induction and on protection against S. iniae infection in olive flounder (Paralichthys olivaceus). The oligomerization of S. iniae enolase by fusion with IMX313 (enolase-IMX313) was verified by non-reducing PAGE, and the antibody titer against enolase in olive flounder immunized with enolase-IMX313 was significantly higher than that in fish immunized with enolase alone. Furthermore, although the survival of olive flounder immunized with enolase alone was low, fish immunized with enolase-IMX313 showed much higher survival (RPS 50%) in accordance with higher serum antibody titer, suggesting that fusion of antigens with IMX313 can be an effective way to enhance protective efficacy of subunit vaccines in olive flounder.
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Formação de Anticorpos , Proteínas de Bactérias/genética , Doenças dos Peixes/imunologia , Linguados , Fosfopiruvato Hidratase/genética , Infecções Estreptocócicas/veterinária , Streptococcus iniae/genética , Animais , Anisóis , Proteínas Aviárias/genética , Proteínas de Bactérias/metabolismo , Doenças dos Peixes/microbiologia , Longevidade , Proteínas Adaptadoras de Sinalização NOD/genética , Fosfopiruvato Hidratase/metabolismo , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Streptococcus iniae/enzimologia , Triazinas , TriazóisRESUMO
Zinc is a trace element that is essential for immune responses. Therefore, changes in cellular zinc levels in specific immune cells may influence inflammatory autoimmune diseases, such as rheumatoid arthritis (RA). However, the regulation of zinc mobilization in immune cells and its role in the pathogenesis of RA are not fully understood. Thus, we investigated the roles of zinc transporters in RA pathogenesis. We demonstrated that ZIP8 was specifically upregulated in CD4+ T cells that infiltrated the inflamed joint and that ZIP8 deficiency in CD4+ T cells abrogated collagen-induced arthritis. ZIP8 deficiency dramatically affected zinc influx in effector T cells and profoundly reduced T cell receptor (TCR)-mediated signaling, including NF-κB and MAPK signaling, which are pathways that are involved in T helper (Th) 17 cell differentiation. Taken together, our findings suggest that ZIP8 depletion in CD4+ T cells attenuates TCR signaling due to insufficient cellular zinc, thereby reducing the function of effector CD4+ T cells, including Th17 cells. Our results also suggest that targeting ZIP8 may be a useful strategy to inhibit RA development and pathogenesis.
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Artrite Experimental/etiologia , Artrite Experimental/metabolismo , Proteínas de Transporte de Cátions/genética , Suscetibilidade a Doenças , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Animais , Artrite Experimental/patologia , Biomarcadores , Proteínas de Transporte de Cátions/metabolismo , Diferenciação Celular/imunologia , Modelos Animais de Doenças , Progressão da Doença , Imunofluorescência , Humanos , Imuno-Histoquímica , Imunofenotipagem , Ativação Linfocitária , Camundongos Knockout , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Subpopulações de Linfócitos T/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/patologiaRESUMO
BACKGROUND: Ribonucleases (RNases) play central roles in the post-transcriptional regulation of mRNA stability. Our preliminary results revealed that the endonuclease Regnase-1 is specifically upregulated in osteoarthritic chondrocytes. We herein explored the possible functions and regulatory mechanisms of Regnase-1 in a mouse model of osteoarthritis (OA). METHODS: The expression and target genes of Regnase-1 were identified by microarray analysis in primary-culture mouse articular chondrocytes. Experimental OA in mice was induced by destabilization of the medial meniscus (DMM). The function of Regnase-1 in DMM-induced post-traumatic OA mice was examined by adenovirus-mediated overexpression or knockdown in knee joint tissues, and also by using Regnase-1 heterozygous knockout mice (Zc3h12a+/-). RESULTS: Among the RNases, Regnase-1 was exclusively upregulated in chondrocytes stimulated with OA-associated catabolic factors. Adenovirus-mediated overexpression or knockdown of Regnase-1 alone in joint tissues did not cause OA-like changes. However, overexpression of Regnase-1 in joint tissues significantly ameliorated DMM-induced post-traumatic OA cartilage destruction, whereas knockdown or genetic ablation of Regnase-1 exacerbated DMM-induced cartilage destruction. Mechanistic studies suggested that Regnase-1 suppresses cartilage destruction by modulating the expression of matrix-degrading enzymes in chondrocytes. CONCLUSION: Our results collectively suggest that upregulated Regnase-1 in OA chondrocytes may function as a chondro-protective effector molecule during OA pathogenesis by forming a negative feedback loop of catabolic signals, such as matrix-degrading enzyme expression, in OA chondrocytes.
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Cartilagem Articular , Condrócitos , Osteoartrite , Ribonucleases/genética , Animais , Endonucleases , Retroalimentação Fisiológica , Camundongos , Camundongos Knockout , Osteoartrite/genéticaRESUMO
OBJECTIVE: Osteoarthritis (OA) is initiated by pathogenic factors produced by multiple stimuli, including mechanical stress, metabolic stress, and/or inflammaging. This study was undertaken to identify novel low-grade inflammation-associated pathogenic mediators of OA. METHODS: Candidate pathogenic molecules were screened using microarray data obtained from chondrocytes exposed to OA-associated catabolic factors. In mice with OA generated by destabilization of the medial meniscus (DMM), low-grade inflammation was induced by a high-fat diet or endotoxemia. Functions of candidate molecules in OA pathogenesis were examined using primary-culture chondrocytes from mice with DMM-induced OA, following intraarticular injection of adenovirus expressing the candidate gene. Specific functions of candidate genes were evaluated using whole-body gene-knockout mice. RESULTS: Bioinformatics analysis identified multiple candidate pathogenic factors that were associated with low-grade inflammation, including components of the Toll-like receptor (TLR) signaling pathways (e.g., TLR-2, TLR-4, lipopolysaccharide binding protein [LBP], and CD14). Overexpression of the individual TLR signaling components in mouse joint tissue did not alter cartilage homeostasis. However, the low-grade inflammation induced by a high-fat diet or endotoxemia markedly enhanced posttraumatic OA cartilage destruction in mice, and this exacerbation of cartilage destruction was significantly abrogated in LBP-/- and CD14-/- mice. Additionally, LBP and CD14 were found to be necessary for the expression of matrix-degrading enzymes in mouse chondrocytes treated with proinflammatory cytokines. CONCLUSION: LBP and CD14, which are accessory molecules of TLRs, are necessary for the exacerbation of posttraumatic OA cartilage destruction resulting from low-grade inflammation, such as that triggered by a high-fat diet or endotoxemia.
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Proteínas de Fase Aguda/metabolismo , Proteínas de Transporte/metabolismo , Mediadores da Inflamação/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Glicoproteínas de Membrana/metabolismo , Osteoartrite/genética , Receptores Toll-Like/metabolismo , Animais , Cartilagem Articular , Condrócitos/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Endotoxemia/complicações , Inflamação , Meniscos Tibiais/metabolismo , Camundongos , Camundongos Knockout , Osteoartrite/etiologia , Transdução de Sinais/genéticaRESUMO
OBJECTIVE: This study aimed 1) to investigate the clinical characteristics of amniotic fluid embolism (AFE) cases clinically diagnosed by maternal fetal medicine (MFM) specialists in Korea, 2) to check the disagreement with 4 recently proposed criteria by the Society for Maternal-Fetal Medicine (SMFM) for research purpose, and 3) to compare maternal outcomes between cases satisfying all 4 criteria and cases with at least 1 missing criterion. METHODS: This study included 12 patients clinically diagnosed with AFE from 7 referral hospitals in Korea. We collected information, including maternal age, symptoms of AFE, the amount of transfusion, and maternal mortality. RESULTS: The median maternal age was 33 years (range, 28-40 years). Regarding symptoms, cardiovascular arrest, hypotension, respiratory compromise, clinical coagulopathy, and neurologic signs were observed in 41.7%, 83.3%, 83.3%, 100%, and 66.7% of the cases, respectively. Among the 12 cases, 5 women died and 2 suffered severe neurologic disability, showing an intact survival rate of 41.7%. Disagreement with all 4 criteria proposed by the SMFM was found in 66.7% of the cases, due to the lack of criteria for disseminated intravascular coagulation or strict onset time (<30 minutes after delivery). There was no difference in maternal mortality and the amount of transfusion between cases satisfying all 4 criteria and cases with at least 1 missing criterion. CONCLUSION: Two-thirds of clinically confirmed AFE cases did not satisfy all 4 criteria proposed by the SMFM, despite similar rates of maternal mortality with cases satisfying all 4 criteria. Our study suggests that there may be some discrepancy between the clinical diagnosis of AFE and the recent diagnostic criteria proposed by the SMFM for research purpose.
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Due to the increasing age of pregnant women, maternal nutrition management is becoming more important. Since pregnant women are more likely to consume sodium and sugars than nonpregnant women of the same age, we investigated whether maternal nutrition intervention focused on the adjustment of salt and sugar intake can help pregnancy outcome. This randomized controlled trial was performed on 142 pregnant women within 22 weeks of gestational age for at least 16 weeks until childbirth. Subjects were unequally assigned to the intervention group (n = 98) and the control group (n = 44). Dietary changes based on perceived taste preferences were evaluated by 24-hr dietary recall and food frequency questionnaires (FFQ) at pre- and postintervention. In the intervention group, while the intakes of energy, protein, and vitamins were maintained, the intakes of sodium (p < .001) and sugar from processed food (p < .05) were significantly reduced after the intervention. The decreases in salt and sugar consumption were more pronounced in the mothers who had a high preference for saltiness and sweetness. The mean neonatal birth weight of the intervention group was significantly greater than the weight of control group, (3,251.5 ± 402.2 g vs. 2,974.5 ± 294.8 g, p < .05). Through this study, nutrition intervention was found to be effective for the formation of healthy eating habits such as reduced salt and sugar intake in pregnant women especially with a high preference for saltiness and sweetness. Also, such specialized maternal nutrition intervention during pregnancy promotes the birth of healthy newborn babies of normal weight.
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OBJECTIVE: The aim of this survey was to study the status of the actual practice in the management of preterm premature rupture of membranes (PPROM) between 34.0 and 36.6 weeks of gestation. METHODS: This survey was designed for obstetricians who work in secondary or tertiary medical institutions and attended the Korean Society of Maternal Fetal Medicine conference held on July 1, 2017, in Korea, using a structured questionnaire consisting of 5 questions. RESULTS: The most commonly used antibiotic was cephalosporin monotherapy (34.5%). Antenatal corticosteroids were applied up to 34.0 weeks of gestation in half of the respondents. The frequency of expectant management was higher than that of immediate delivery in women with PPROM between 34.0 and 36.6 weeks of gestation (57.4%). The most important factor in determining immediate delivery was the symptoms of chorioamnionitis. CONCLUSION: The present survey showed a considerable variation in the actual management of PPROM in women, especially the optimal timing of delivery. More evidenced-based studies with statistical power are required to decrease the heterogeneity of clinical practice.
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We previously showed that mice with knockout of Cytl1, a functionally uncharacterized cytokine candidate, exhibit normal endochondral ossification and long-bone development. Here, we investigated the potential functions of CYTL1 in bone homeostasis. We found that Cytl1-/- mice exhibited higher bone mass than wild-type littermates and resisted ovariectomy-induced bone resorption. This led us to investigate the functions of CYTL1 in the osteogenesis and osteoclastogenesis of bone marrow-derived stem cells. CYTL1 was down-regulated during the osteogenesis of human mesenchymal stem cells (hMSCs). The osteogenesis of hMSCs was inhibited by overexpression or exogenous treatment of CYTL1, but enhanced by CYTL1 knockdown. CYTL1 decreased osteogenesis by inhibiting RUNX2 and promoted proliferation among undifferentiated hMSCs, but stimulated apoptosis among osteogenically differentiating cells. Finally, Cytl1-/- mice exhibited inhibition of osteoclast activity and the osteoclastogenesis of bone marrow-derived macrophages. Our results collectively suggest that CYTL1 negatively regulates the osteogenesis of MSCs and positively regulates osteoclastogenesis to modulate bone mass in mice.
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Proteínas Sanguíneas/metabolismo , Citocinas/metabolismo , Macrófagos/citologia , Macrófagos/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Animais , Proteínas Sanguíneas/biossíntese , Reabsorção Óssea , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Diferenciação Celular/fisiologia , Citocinas/biossíntese , Citocinas/genética , Homeostase , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteogênese , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: Osteoarthritis (OA) appears to be associated with various metabolic disorders, but the potential contribution of amino acid metabolism to OA pathogenesis has not been clearly elucidated. Here, we explored whether alterations in the amino acid metabolism of chondrocytes could regulate OA pathogenesis. METHODS: Expression profiles of amino acid metabolism-regulating genes in primary-culture passage 0 mouse chondrocytes were examined by microarray analysis, and selected genes were further characterised in mouse OA chondrocytes and OA cartilage of human and mouse models. Experimental OA in mice was induced by destabilisation of the medial meniscus (DMM) or intra-articular (IA) injection of adenoviruses expressing catabolic regulators. The functional consequences of arginase II (Arg-II) were examined in Arg2-/- mice and those subjected to IA injection of an adenovirus encoding Arg-II (Ad-Arg-II). RESULTS: The gene encoding Arg-II, an arginine-metabolising enzyme, was specifically upregulated in chondrocytes under various pathological conditions and in OA cartilage from human patients with OA and various mouse models. Adenovirus-mediated overexpression of Arg-II in mouse joint tissues caused OA pathogenesis, whereas genetic ablation of Arg2 in mice (Arg2-/-) abolished all manifestations of DMM-induced OA. Mechanistically, Arg-II appears to cause OA cartilage destruction at least partly by upregulating the expression of matrix-degrading enzymes (matrix metalloproteinase 3 [MMP3] and MMP13) in chondrocytes via the nuclear factor (NF)-κB pathway. CONCLUSIONS: Our results indicate that Arg-II is a crucial regulator of OA pathogenesis in mice. Although chondrocytes of human and mouse do not identically, but similarly, respond to Arg-II, our results suggest that Arg-II could be a therapeutic target of OA pathogenesis.
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Arginase/fisiologia , Artrite Experimental/enzimologia , Cartilagem Articular/enzimologia , Condrócitos/enzimologia , Osteoartrite/enzimologia , Animais , Artrite Experimental/induzido quimicamente , Modelos Animais de Doenças , Humanos , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Camundongos , Osteoartrite/induzido quimicamente , Regulação para CimaAssuntos
Hipotermia/diagnóstico , Vasculite Associada ao Lúpus do Sistema Nervoso Central/diagnóstico , Complicações na Gravidez/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Hipotermia/etiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/complicações , GravidezRESUMO
The artificially synthesized polyinosinic-polycytidylic acid (poly IC) has been widely used to induce type I IFN responses in various vertebrates including fish. However, as poly IC is too expensive to use in aquaculture, the development of another economical long dsRNA producing method is needed to practically use long dsRNAs in aquaculture farms for the control of infectious diseases. In the present study, to produce long dsRNAs economically, we developed a novel long dsRNA production system based on the RNase III gene deleted auxotrophic mutant E. tarda (ΔalrΔrncΔasd E. tarda) and a long dsRNA-producing vector that was equipped with two modified λ phage PR promoters arranged in a head-to-head fashion. As the present genetically engineered E. tarda cannot live without supplementation of d-alanine and DAP, environmental and medicinal risks are minimized. Olive flounder (Paralichthys olivaceus) fingerlings administered the long dsRNA-producing auxotrophic E. tarda mutant (Δalr ΔrncΔasd E. tarda) showed significantly higher expressions of TLR22, Mx1, and ISG15 genes, indicating a potential to increase type I interferon responses.
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Aquicultura/métodos , Proteínas de Bactérias/metabolismo , Edwardsiella tarda/genética , Linguados/imunologia , RNA Bacteriano/metabolismo , RNA de Cadeia Dupla/administração & dosagem , Ribonuclease III/genética , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/metabolismo , Animais , Técnicas de Inativação de Genes/veterinária , Imunização/veterinária , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/metabolismoRESUMO
We previously reported peritoneal innate-like integrin α4 (CD49d)highCD4+ T cells that provided help for B-1a cells. Here we analyzed the expression of various integrin chains on the peritoneal and pleural integrin α4highCD4+ T cells and investigated the functional heterogeneity of the subpopulations based on the integrin expression. Pleural cavity contained a lower ratio of integrin α4highCD4+ T cells to integrin α4lowCD4+ T cells than peritoneal cavity, but the pleural integrin α4highCD4+ T cells have the same characteristics of the peritoneal integrin α4highCD4+ T cells. Most of integrin α4highCD4+ T cells were integrin ß1highß7-, but a minor population of integrin α4highCD4+ T cells was integrin ß1+ß7+. Interestingly, the integrin α4highß1highß7- CD4+ T cells expressed high levels of integrin α4ß1 and α6ß1, whereas integrin α4highß1+ß7+ CD4+ T cells expressed high levels of integrin α4ß1 and α4ß7, suggesting an alternative expression of integrin α6ß1 or α4ß7 in combination with α4ß1 in respective major and minor populations of integrin α4highCD4+ T cells. The minor population, integrin α4highß1+ß7+ CD4+ T cells, were different from the integrin α4highß1highß7- CD4+ T cells in that they secreted a smaller amount of Th1 cytokines upon stimulation and expressed lower levels of Th1-related chemokine receptors CCR5 and CXCR3 than the integrin α4highß1highß7- CD4+ T cells. In summary, the innate-like integrin α4highCD4+ T cells could be divided into 2 populations, integrin α4ß1+α6ß1+α4ß7- and α4ß1+α6ß1-α4ß7+ cells. The functional significance of serosal integrin α4ß7+ CD4+ T cells needed to be investigated especially in view of mucosal immunity.
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Preeclampsia is one of the most important and complexed disorders for women's health. Searching for novel proteins as biomarkers to reveal pathogenesis, proteomic approaches using 2DE has become a valuable tool to understanding of preeclampsia. To analyze the proteomic profiling of preclamptic placenta compared to that of normal pregnancy for better understanding of pathogenesis in preeclampsia, placentas from each group were handled by use of proteomics approach using 2DE combined with MALDI-TOF-MS. The 20 spots of showing differences were analysed and identified. Among differentially expressed protein spots Hsp 27 and Hsp 70 were selected for validation using Western blot analysis. In preeclamptic placenta 9 differentially expressed proteins were down-regulated with Hsp 70, serum albumin crystal structure chain A, lamin B2, cytokeratin 18, actin cytoplasmic, alpha fibrinogen precursor, septin 2, dihydrolipoamide branched chain transacylase E2 and firbrinogen beta chain. The 11 up-regulated proteins were fibrinogen gamma, cardiac muscle alpha actin proprotein, cytokeratin 8, calumenin, fibrinogen fragment D, F-actin capping protein alpha-1 subunit, Hsp 27, Hsp 40, annexin A4, enoyl-CoA delta isomerase and programmed cell death protein 6. The western blot analysis for validation also showed significant up-regulation of Hsp 27 and down-regulation of Hsp 70 in the placental tissues with preeclmaptic pregnancies. This proteomic profiling of placenta using 2DE in preeclampsia successfully identifies various proteins involved in apoptosis, mitochondrial dysfunction, as well as three Hsps with altered expression, which might play a important role for the understanding of pathogenesis in preeclampsia.
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Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez/metabolismo , Proteoma/metabolismo , Adulto , Feminino , Humanos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
AIM: Inflammation of the upper genital tract causes pelvic inflammatory disease (PID), which may be complicated by pelvic abscesses, such as pyosalpinx and tubo-ovarian abscess (TOA). This study aimed to determine the clinical differences between pyosalpinx and TOA in patients with PID. MATERIAL AND METHODS: We retrospectively evaluated 458 female patients who were admitted to Hallym University Kang Dong Sacred Heart Hospital for a clinical diagnosis of PID from 1 January 2007 to 30 April 2012. Sociodemographic, clinical and laboratory data were compared among the non-abscess, pyosalpinx, and TOA groups. RESULTS: We identified 110 patients (24%) diagnosed with pelvic abscess associated with PID, including 34 with pyosalpinx and 76 with TOA. The pyosalpinx group had shorter hospital stays (P = 0.007), lower C-reactive protein levels (P = 0.015), smaller mass sizes (P < 0.001), and fewer surgical interventions (P < 0.001) than the TOA group. CONCLUSIONS: Pyosalpinx is a less severe form of PID that leads to shorter hospital stays and more favorable outcomes than TOA.
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Abscesso/patologia , Doenças das Tubas Uterinas/patologia , Doenças Ovarianas/patologia , Doença Inflamatória Pélvica/patologia , Salpingite/patologia , Adulto , Feminino , Hospitalização , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to evaluate indications, efficacy, and complications associated with pelvic arterial embolization (PAE) for postpartum hemorrhage (PPH). METHODS: We retrospectively reviewed the medical records of 117 consecutive patients who underwent PAE for PPH between January 2006 and June 2013. RESULTS: In our single-center study, 117 women underwent PAE to control PPH refractory to conservative management including uterine massage, use of uterotonic agents, surgical repair of genital tract lacerations, and removal of retained placental tissues. Among 117 patients, 69 had a vaginal delivery and 48 had a Cesarean section. The major indication for embolization was uterine atony (54.7%). Other causes were low genital tract lacerations (21.4%) and abnormal placentation (14.5%). The procedure showed a clinical success rate of 88.0% with 14 cases of PAE failure; there were 4 hemostatic hysterectomies and 10 re-embolizations. On univariate analysis, PAE failure was associated with overt disseminated intravascular coagulation (P=0.009), transfusion of more than 10 red blood cell units (RBCUs, P=0.002) and embolization of both uterine and ovarian arteries (P=0.003). Multivariate analysis showed that PAE failure was only associated with transfusions of more than 10 RBCUs (odds ratio, 8.011; 95% confidence interval, 1.531-41.912; P=0.014) and embolization of both uterine and ovarian arteries (odds ratio, 20.472; 95% confidence interval, 2.715-154.365; P=0.003), which were not predictive factors, but rather, were the results of longer time for PAE. Three patients showed uterine necrosis and underwent hysterectomy. CONCLUSION: PAE showed high success rates, mostly without procedure-related complications. Thus, it is a safe and effective adjunct or alternative to hemostatic hysterectomy, when primary management fails to control PPH.
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OBJECTIVE: To compare effectiveness on correcting cranial and ear asymmetry between helmet therapy and counter positioning for deformational plagiocephaly (DP). METHODS: Retrospective data of children diagnosed with DP who visited our clinic from November 2010 to October 2012 were reviewed. Subjects ≤10 months of age who showed ≥10 mm of diagonal difference were included for analysis. For DP treatment, information on both helmet therapy and counter positioning was given and either of the two was chosen by each family. Head circumference, cranial asymmetry measurements including diagonal difference, cranial vault asymmetry index, radial symmetry index, and ear shift were obtained by 3-dimensional head-surface laser scan at the time of initiation and termination of therapy. RESULTS: Twenty-seven subjects were included: 21 had helmet therapy and 6 underwent counter positioning. There was no significant difference of baseline characteristics, head circumferences and cranial asymmetry measurements at the initiation of therapy. The mean duration of therapy was 4.30±1.27 months in the helmet therapy group and 4.08±0.95 months in the counter positioning group (p=0.770). While cranial asymmetry measurements improved in both groups, significantly more improvement was observed with helmet therapy. There was no significant difference of the head circumference growth between the two groups at the end of therapy. CONCLUSION: Helmet therapy resulted in more favorable outcomes in correcting cranial and ear asymmetry than counter positioning on moderate to severe DP without compromising head growth.