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1.
Sci Adv ; 10(9): eadk6425, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38416834

RESUMO

To develop a universal coronavirus (CoV) vaccine, long-term immunity against multiple CoVs, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, Middle East respiratory syndrome (MERS)-CoV, and future CoV strains, is crucial. Following the 2015 Korean MERS outbreak, we conducted a long-term follow-up study and found that although neutralizing antibodies and memory T cells against MERS-CoV declined over 5 years, some recovered patients exhibited increased antibody levels during the COVID-19 pandemic. This likely resulted from cross-reactive immunity induced by SARS-CoV-2 vaccines or infections. A significant correlation in antibody responses across various CoVs indicates shared immunogenic epitopes. Two epitopes-the spike protein's stem helix and intracellular domain-were highly immunogenic after MERS-CoV infection and after SARS-CoV-2 vaccination or infection. In addition, memory T cell responses, especially polyfunctional CD4+ T cells, were enhanced during the pandemic, correlating significantly with MERS-CoV spike-specific antibodies and neutralizing activity. Therefore, incorporating these cross-reactive and immunogenic epitopes into pan-CoV vaccine formulations may facilitate effective vaccine development.


Assuntos
COVID-19 , Coronavírus da Síndrome Respiratória do Oriente Médio , Humanos , COVID-19/epidemiologia , Vacinas contra COVID-19 , Pandemias , Seguimentos , SARS-CoV-2 , Imunidade Adaptativa , Epitopos
2.
J Clin Med ; 13(1)2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38202265

RESUMO

BACKGROUND: Middle East respiratory syndrome (MERS) is a lower respiratory tract disease caused by a beta coronavirus (CoV) called MERS-CoV, characterized by a high mortality rate. We aimed to evaluate the association between genetic variation in killer cell immunoglobulin-like receptors (KIRs) and the risk of MERS in South Koreans. METHODS: KIR genes were genotyped by multiplex polymerase chain reaction with sequence-specific primers (PCR-SSP). A case-control study was performed to identify the odds ratios (OR) of KIR genes for MERS and the association of KIR genes and their ligands, human leukocyte antigens (HLA) genes. RESULTS: KIR2DS4D and KIR3DP1F showed higher frequencies in the group of all patients infected with MERS-CoV than in the control group (p = 0.023, OR = 2.4; p = 0.039, OR = 2.7). KIR2DL1, KIR2DP1, and KIR3DP1D were significantly associated with moderate/mild (Mo/Mi) cases. KIR2DL2, KIR2DS1, and KIR3DP1F were affected in severe cases. When we investigated the association between KIR genes and their ligands in MERS patient and control groups, KIR3DL1+/Bw4(80I)+, KIR3DL1+/Bw6+, KIR3DL1+/Bw6-, KIR2DS1+/C2+, and KIR3DS+/Bw4(80I)+ were associated with MERS. KIR3DL1+/Bw6- was found in Mo/Mi cases. KIR2DS1+/C2+ and KIR2DS2+/C1+ were found in severe cases. CONCLUSION: Further investigations are needed to prove the various immune responses of MERS-CoV-infected cells according to variations in the KIR gene and ligand gene. A treatment strategy based on current research on the KIR gene and MERS-CoV will suggest potential treatment targets.

3.
J Pediatric Infect Dis Soc ; 11(6): 267-273, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35275210

RESUMO

BACKGROUND: The immunologic features of children with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not clearly delineated. This study was conducted to evaluate SARS-CoV-2-specific antibody responses in children with COVID-19. METHODS: The levels of anti-spike (S) IgG, anti-SARS-CoV-2 IgG, and neutralizing antibody (NAb) were measured during various time points in children <19 years of age with COVID-19 in South Korea from February 2020 to September 2020. RESULTS: One hundred sixty-five blood samples from 114 children with COVID-19 (43.9% asymptomatic and 56.1% mildly symptomatic) were analyzed. In both asymptomatic and mildly symptomatic children, the positive rates of anti-S IgG, anti-SARS-CoV-2 IgG, and NAb were low within 7 days after onset, but they soon reached 100% 14 to <28 days after onset. In symptomatic children, the geometric mean titers (GMTs) of antibodies were all below the positive cutoff during the first 2 weeks from onset and peaked at 28 to <56 days (5.6 for anti-S IgG, 383.6 for anti-SARS-CoV-2 IgG, and 55.0 for NAb, P < .001, respectively). Antibody levels remained detectable up to 3 months after infection. The antibody GMTs during the period 14 to <56 days after symptom onset were highest in children aged 0-4 years. CONCLUSIONS: These results collectively present the humoral immune responses during SARS-CoV-2 infection in children. A further longitudinal study is needed to thoroughly understand the immune system and for effective vaccine development in children during the COVID-19 pandemic.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Criança , Humanos , Imunoglobulina G , Pandemias , Adulto Jovem
4.
Clin Infect Dis ; 75(4): 596-603, 2022 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893799

RESUMO

BACKGROUND: Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease caused by a zoonotic betacoronavirus. The development of effective vaccines and control measures requires a thorough understanding of the immune response to this viral infection. METHODS: We investigated cellular immune responses up to 5 years after infection in a cohort of 59 MERS survivors by performing enzyme-linked immunospot assay and intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with synthetic viral peptides. RESULTS: Memory T-cell responses were detected in 82%, 75%, 69%, 64%, and 64% of MERS survivors from 1-5 years post-infection, respectively. Although the frequency of virus-specific interferon gamma (IFN-γ)-secreting T cells tended to be higher in moderately/severely ill patients than in mildly ill patients during the early period of follow-up, there was no significant difference among the different clinical severity groups across all time points. While both CD4+ and CD8+ T cells were involved in memory T-cell responses, CD4+ T cells persisted slightly longer than CD8+ T cells. Both memory CD4+ and CD8+ T cells recognized the E/M/N proteins better than the S protein and maintained their polyfunctionality throughout the period examined. Memory T-cell responses correlated positively with antibody responses during the initial 3-4 years but not with maximum viral loads at any time point. CONCLUSIONS: These findings advance our understanding of the dynamics of virus-specific memory T-cell immunity after MERS-coronavirus infection, which is relevant to the development of effective T cell-based vaccines.


Assuntos
Infecções por Coronavirus , Coronavírus da Síndrome Respiratória do Oriente Médio , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Humanos , Memória Imunológica , Leucócitos Mononucleares , Células T de Memória , Sobreviventes
5.
Clin Microbiol Infect ; 28(2): 292-296, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34139334

RESUMO

OBJECTIVES: We aimed to assess the longevity of spike-specific antibody responses and neutralizing activity in the plasma of recovered Middle East respiratory syndrome (MERS) patients. METHODS: We traced the antibody responses and neutralizing activity against MERS coronavirus (MERS-CoV) in peripheral blood samples collected from 70 recovered MERS patients for 5 years after the 2015 MERS outbreak in South Korea. We also measured the half-life of neutralizing antibody titres in the longitudinal specimens. RESULTS: The seropositivity rate persisted for up to 4 years (50.7-56.1%), especially in MERS patients who suffered from severe pneumonia, and then decreased (35.9%) in the fifth year. Although the spike-specific antibody responses decreased gradually, the neutralizing antibody titres decreased more rapidly (half-life: 20 months) in 19 participants without showing negative seroconversion during the study period. Only five (26.3%) participants had neutralizing antibody titres greater than 1/1000 of PRNT50, and a high neutralizing antibody titre over 1/5000 was not detected in the participants at five years after infection. DISCUSSION: The seropositivity rate of the recovered MERS patients persisted up to 4 years after infection and significantly dropped in the fifth year, whereas the neutralizing antibody titres against MERS-CoV decreased more rapidly and were significantly reduced at 4 years after infection.


Assuntos
Infecções por Coronavirus , Coronavírus da Síndrome Respiratória do Oriente Médio , Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções por Coronavirus/epidemiologia , Seguimentos , Humanos , Glicoproteína da Espícula de Coronavírus
6.
Immun Inflamm Dis ; 10(1): 111-116, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34637605

RESUMO

INTRODUCTION: Middle East Respiratory Syndrome (MERS) caused by MERS-coronavirus (CoV) is a lower respiratory tract disease characterized by a high mortality rate. MERS-CoV spread from Saudi Arabia to other countries, including South Korea. Dysfunction of the human leukocyte antigen (HLA) system has many effects due to genetic complexity and its role in the adaptive immune response. We investigated the association of HLA class I and II alleles with MERS-CoV in 32 patients with MERS. METHODS: HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 were genotyped by polymerase chain reaction sequence-based typing. RESULTS: HLA-DQB1*03:02 are significantly associated with moderate/mild cases of MERS-CoV. Other alleles are no statistical significance. CONCLUSIONS: Treatment strategies based on current research on the HLA gene and MERS-CoV will provide potential therapeutic targets.


Assuntos
Genes MHC da Classe II , Genes MHC Classe I , Coronavírus da Síndrome Respiratória do Oriente Médio , Cadeias beta de HLA-DQ/genética , Humanos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , República da Coreia
7.
Clin Infect Dis ; 73(3): e550-e558, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-32898238

RESUMO

BACKGROUND: Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap. METHODS: We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge. RESULTS: Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (> 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss. CONCLUSIONS: High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.


Assuntos
Infecções por Coronavirus , Coronavírus da Síndrome Respiratória do Oriente Médio , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções por Coronavirus/tratamento farmacológico , Humanos , Camundongos , República da Coreia , Glicoproteína da Espícula de Coronavírus
8.
Emerg Infect Dis ; 25(6): 1161-1168, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30900977

RESUMO

The unexpectedly large outbreak of Middle East respiratory syndrome in South Korea in 2015 was initiated by an infected traveler and amplified by several "superspreading" events. Previously, we reported the emergence and spread of mutant Middle East respiratory syndrome coronavirus bearing spike mutations (I529T or D510G) with reduced affinity to human receptor CD26 during the outbreak. To assess the potential association of spike mutations with superspreading events, we collected virus genetic information reported during the outbreak and systemically analyzed the relationship of spike sequences and epidemiology. We found sequential emergence of the spike mutations in 2 superspreaders. In vivo virulence of the mutant viruses seems to decline in human patients, as assessed by fever duration in affected persons. In addition, neutralizing activity against these 2 mutant viruses in serum samples from mice immunized with wild-type spike antigen were gradually reduced, suggesting emergence and wide spread of neutralization escapers during the outbreak.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Mutação , Adulto , Idoso , Anticorpos Neutralizantes/imunologia , Doenças Transmissíveis Emergentes/história , Doenças Transmissíveis Emergentes/imunologia , Infecções por Coronavirus/história , Infecções por Coronavirus/imunologia , Surtos de Doenças , Feminino , Genótipo , História do Século XXI , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Testes de Neutralização , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia
9.
Clin Infect Dis ; 68(6): 984-992, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30060038

RESUMO

BACKGROUND: An understanding of immune responses against the Middle East respiratory syndrome (MERS) is important for the development of treatments and preventive measures. Here, we investigated the spectrum of immune responses occurring in patients with MERS during the early period of infection. METHODS: We obtained peripheral blood samples from 27 hospitalized patients recruited during the epidemic that occurred in 2015 in South Korea. Plasma cytokines/chemokines and antibodies were quantified. Virus-specific T cells were examined by intracellular cytokine staining after stimulation of peripheral blood mononuclear cells with overlapping peptides spanning whole virus structural proteins. RESULTS: At the acute phase of infection, elevated levels of plasma proinflammatory cytokines/chemokines were detected in proportion to the severity of the disease. Distinctively high frequencies of MERS coronavirus-reactive CD8+ T cells were also observed in patients with severe/moderate illness, whereas antibody and CD4+ T-cell responses were minimally detected at this stage. At the convalescent phase, disease severity-dependent antibody responses emerged and antigen-reactive cells were identified in both T-cell subsets. These T cells belonged to the T-helper 1 or type 1 cytotoxic T cell subtypes. While CD8+ T cells responded preferentially to the viral S protein compared with E/M/N proteins, especially at the acute stage, slightly more CD4+ T cells recognized E/M/N proteins compared with S protein at the convalescent phase. CONCLUSIONS: Our findings show an association between the early CD8+ T-cell response and the severity of the infection, and also provide basic information that may help to prepare effective control strategies for MERS in humans.


Assuntos
Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Infecções por Coronavirus/epidemiologia , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Resultados da Assistência ao Paciente , República da Coreia , Subpopulações de Linfócitos T/imunologia , Adulto Jovem
10.
J Korean Med Sci ; 33(24): e169, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29892209

RESUMO

This nationwide, prospective cohort study evaluated pulmonary function and radiological sequelae according to infection severity in 73 survivors from the 2015 Middle East respiratory syndrome (MERS) outbreak in Korea. Patients with severe pneumonia in MERS-coronavirus infection had more impaired pulmonary function than those with no or mild pneumonia at the 1-year follow-up, which was compatible with the radiological sequelae. Severe pneumonia significantly impairs pulmonary function and makes long radiological sequelae in MERS.


Assuntos
Infecções por Coronavirus/patologia , Pulmão/fisiopatologia , Pneumonia/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/complicações , Feminino , Volume Expiratório Forçado , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Estudos Prospectivos , República da Coreia , Índice de Gravidade de Doença , Sobreviventes
11.
Genome Res ; 2018 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-29472270

RESUMO

Here, we report that CRISPR guide RNAs (gRNAs) with a 5'-triphosphate group (5'-ppp gRNAs) produced via in vitro transcription trigger RNA-sensing innate immune responses in human and murine cells, leading to cytotoxicity. 5'-ppp gRNAs in the cytosol are recognized by DDX58, which in turn activates type I interferon responses, causing up to ∼80% cell death. We show that the triphosphate group can be removed by a phosphatase in vitro and that the resulting 5'-hydroxyl gRNAs in complex with Cas9 or Cpf1 avoid innate immune responses and can achieve targeted mutagenesis at a frequency of 95% in primary human CD4+ T cells. These results are in line with previous findings that chemically synthesized sgRNAs with a 5'-hydroxyl group are much more efficient than in vitro-transcribed (IVT) sgRNAs in human and other mammalian cells. The phosphatase treatment of IVT sgRNAs is a cost-effective method for making highly active sgRNAs, avoiding innate immune responses in human cells.

12.
Int J Antimicrob Agents ; 51(5): 762-767, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29408226

RESUMO

Clostridium difficile infection (CDI) is a major healthcare-associated infection. The aim of this study was to investigate the genetic relatedness of the endemic C. difficile PCR ribotype 018 strains in an institution and changes to their characteristics during a five-year period. A total of 207 isolates from inpatients at Hanyang University Hospital from 2009 to 2013 were analysed using multilocus variable-number tandem-repeat analysis (MLVA). Minimum inhibitory concentrations (MICs) of several antibiotics were determined. In total, 204 (98.6%) were genetically related, with a summed tandem-repeat distance (STRD) ≤ 10. Minimum-spanning-tree analysis identified 78 MLVA types, categorized into six clonal complexes (CCs). The largest cluster, CC-I, included 51 MLVA types from 148 isolates (71.5%) and the second largest cluster, CC-II, included 10 MLVA types from 36 isolates (17.4%). Resistance rates for antibiotics were: clindamycin (CLI), 97.6%; moxifloxacin (MXF), 98.6%; vancomycin (VAN), 1.4%; and rifaximin (RFX), 8.2%. All isolates were susceptible to piperacillin/tazobactam (TZP) and metronidazole (MTZ). Comparing the MICs of antibiotics for the isolates each year from 2009 to 2013, MICs of antibiotics that promote CDI, such as CLI, MXF, TZP and RFX, increased over the five-year period (P-value by Kruskal-Wallis test: < 0.0001, <0.0001, <0.0001, and <0.0001 respectively); however, MICs of VAN or MTZ, antibiotics for treatment of CDI, did not increase or decreased over the same time period (P-value by Kruskal-Wallis test: 0.166, <0.0001). C. difficile RT018 isolates in a tertiary hospital over a five-year period presented a close clonal relationship. MICs of antibiotics promoting CDI increased with this clonal expansion.


Assuntos
Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/genética , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Reação em Cadeia da Polimerase , Prevalência , República da Coreia , Ribotipagem , Centros de Atenção Terciária
13.
Xenotransplantation ; 25(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29057561

RESUMO

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


Assuntos
Antígenos CD40/imunologia , Imunossupressores/farmacologia , Transplante das Ilhotas Pancreáticas/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Transplante Heterólogo , Animais , Ligante de CD40/imunologia , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Xenoenxertos/imunologia , Terapia de Imunossupressão/métodos , Transplante das Ilhotas Pancreáticas/métodos , Leucócitos Mononucleares/imunologia , Macaca mulatta , Transplante Heterólogo/métodos
14.
Am J Infect Control ; 46(4): 436-440, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29153641

RESUMO

BACKGROUND: Transmission of Middle East respiratory syndrome (MERS) to health care personnel (HCP) is a major concern. This study aimed to review cases of MERS-related events, such as development of MERS-like symptoms or exposure to patients. METHODS: A MERS screening clinic (MSC) for HCP was setup in the National Medical Center during the MERS outbreak in 2015. Clinical and laboratory data from HCP who visited the MSC were retrospectively reviewed. Additionally, these data were compared with the results of postoutbreak questionnaire surveys and interviews about MERS-related symptoms and risk-related events. RESULTS: Of the 333 HCP who participated in MERS patient care, 35 HCP (10.5%) visited the MSC for MERS-like symptoms. No one was infected with MERS, and the most common symptom was fever (68.6%) followed by cough (34.3%). However, 106 of 285 postoutbreak survey participants experienced at least 1 MERS-related symptom and 26 reported exposure to patients without appropriate personal protective equipment, whereas only 4 HCP visited the MSC to report exposure events. CONCLUSIONS: Although a considerable number of HCP experienced MERS-related symptoms or unprotected exposure during MERS patient care, some did not take appropriate action. These findings imply that for infection control strategy to be properly performed, education should be strengthened so that HCP can accurately recognize the risk situation and properly notify the infection control officer.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Surtos de Doenças , Pessoal de Saúde , Coronavírus da Síndrome Respiratória do Oriente Médio , Instituições de Assistência Ambulatorial , Humanos , República da Coreia/epidemiologia , Estudos Retrospectivos
16.
Xenotransplantation ; 23(4): 300-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27387829

RESUMO

BACKGROUND: Islet allotransplantation is a promising way to treat some type 1 diabetic (T1D) patients with frequent hypoglycemic unawareness, and islet xenotransplantation is emerging to overcome the problem of donor organ shortage. Our recent study showing reproducible long-term survival of porcine islets in non-human primates (NHPs) allows us to examine whether autologous regulatory T-cell (Treg) infusion at peri-transplantation period would induce transplantation tolerance in xenotransplantation setting. METHODS: Two diabetic rhesus monkeys were transplanted with porcine islets from wild-type adult Seoul National University (SNU) miniature pigs with immunosuppression by anti-thymoglobulin (ATG), cobra venom factor, anti-CD154 monoclonal antibody (mAb), and sirolimus. CD4(+) CD25(high) CD127(low) autologous regulatory T cells from the recipients were isolated, ex vivo expanded, and infused at the peri-transplantation period. Blood glucose and porcine C-peptide from the recipients were measured up to 1000 days. Maintenance immunosuppressants including a CD40-CD154 blockade were deliberately discontinued to confirm whether transplantation tolerance was induced by adoptively transferred Tregs. RESULTS: After pig islet transplantation via portal vein, blood glucose levels of diabetic recipients became normalized and maintained over 6 months while in immunosuppressive maintenance with a CD40-CD154 blockade and sirolimus. However, the engrafted pig islets in the long-term period were fully rejected by activated immune cells, particularly T cells, when immunosuppressants were stopped, showing a failure of transplantation tolerance induction by autologous Tregs. CONCLUSIONS: Taken together, autologous Tregs infused at the peri-transplantation period failed to induce transplantation tolerance in pig-to-NHP islet xenotransplantation setting.


Assuntos
Sobrevivência de Enxerto/imunologia , Linfócitos T Reguladores/imunologia , Tolerância ao Transplante/imunologia , Transplante Heterólogo , Animais , Diabetes Mellitus Experimental , Tolerância Imunológica/efeitos dos fármacos , Terapia de Imunossupressão/métodos , Imunossupressores/farmacologia , Transplante das Ilhotas Pancreáticas , Primatas , Suínos , Transplante Heterólogo/métodos
17.
Tuberculosis (Edinb) ; 95(6): 758-763, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26520601

RESUMO

Tuberculosis remains a highly prevalent infectious disease worldwide. Identification of the immune parameters that differentiate active disease from latent infection will facilitate the development of efficient control measures as well as new diagnostic modalities for tuberculosis. Here, we investigated the cytokine production profiles of monocytes and CD4(+) T lymphocytes upon encountering mycobacterial antigens. In addition, cytokines and lipid mediators with immune-modulating activities were examined in plasma samples ex vivo. Comparison of these parameters in active tuberculosis patients and healthy subjects with latent infection revealed that, active tuberculosis was associated with diminished Th1-type cytokine secretion from CD4(+) T cells and less augmented inflammatory cytokine secretion from monocytes induced by IFN-γ than that in latent tuberculosis infection. In addition, a higher plasma concentration of lipoxin A4 and lower ratio of prostaglandin E2 to lipoxin A4 were observed in active cases than in latent infections. These findings have implications for preparing new therapeutic strategies and for differential diagnosis of the two types of tuberculosis infection.


Assuntos
Antígenos de Bactérias/imunologia , Linfócitos T CD4-Positivos/imunologia , Citocinas/imunologia , Tuberculose Latente/diagnóstico , Monócitos/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/diagnóstico , Adulto , Idoso , Biomarcadores/sangue , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/microbiologia , Células Cultivadas , Técnicas de Cocultura , Citocinas/sangue , Diagnóstico Diferencial , Dinoprostona/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas Imunoenzimáticas , Tuberculose Latente/sangue , Tuberculose Latente/imunologia , Tuberculose Latente/microbiologia , Lipoxinas/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Monócitos/microbiologia , Valor Preditivo dos Testes , Tuberculose/sangue , Tuberculose/imunologia , Tuberculose/microbiologia , Adulto Jovem
18.
Clin Immunol ; 159(1): 37-46, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25931385

RESUMO

The development of diagnostic tests that predict the progression of latent tuberculosis infection to active disease is pivotal for the eradication of tuberculosis. As an initial step to achieve this goal, our study's aim was to identify biomarkers that differentiate active from latent tuberculosis infection. We compared active and latent tuberculosis infection groups in terms of the precursor frequency, functional subset differentiation, and senescence/exhaustion surface marker expression of antigen-specific CD4(+) T cells, which were defined as dividing cells upon their encountering with Mycobacterium (M.) tuberculosis antigens. Among several parameters shown to have statistically significant differences between the two groups, the frequency of CD57-expressing cells could differentiate effectively between active disease and latent infection. Our results suggest that the expression of CD57 in M. tuberculosis-reactive CD4(+) T cells could be a promising candidate biomarker with which to identify individuals with latent tuberculosis infection prone to progression to active disease.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Antígenos CD57/metabolismo , Tuberculose Latente/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Tuberculose Pulmonar/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Tuberculose Latente/diagnóstico , Leucócitos Mononucleares , Masculino , Pessoa de Meia-Idade , Tuberculose Pulmonar/diagnóstico , Adulto Jovem
19.
J Anim Sci Technol ; 56: 19, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26290708

RESUMO

The purpose of this study was to investigate crucial factors on HACCP system implementation in domestic livestock product plants, and to offer job satisfaction and the career prospect of HACCP system operators. The survey was carried out by selecting 150 HACCP system operators who implemented HACCP system. The respondents claimed that the most important contents in HACCP system operation were to assemble HACCP team (21.8%), and the second was to monitoring (20.0%). Documentation and recording (16.9%) and verification (11.1%) were followed. The respondents answered the major factor in sanitation management was cleaning/washing/disinfection (18.9%) and inspection (18.4%). The results showed that there were significant differences in the prospect of occupation in HACCP system operator by the gender (p < 0.015), age, livestock product facilities, service period, and position (p < 0.001). The respondents from HACCP system operator were satisfied with their job (73%) and also showed optimistic prospect of occupation (82%).

20.
Korean J Food Sci Anim Resour ; 34(2): 185-91, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26760937

RESUMO

This study was performed to determine the meat quality characteristics of pork loin and belly from 3 different three-way crossbred pigs: Yorkshire × Landrace × Duroc (YLD), Yorkshire × Chester White × Yorkshire (YCY), and Yorkshire × Berkshire × Duroc (YBD). Each of the twenty crossed pigs were randomly selected with their live weights at the range of 110-120 kg. After being slaughtered and cooled at 0℃ for 24 h in a chilling room, the parts of loin and belly on the left side of the cooled carcasses were cut and prepared for analysis. The intramuscular fat contents of the loins from YLD were higher than those of the other crossbreds (p<0.05), and the YCY bellies had the highest moisture contents (p<0.05). Water holding capacity (WHC) of the loins from YCY were higher than the other crossbreds (p<0.05). Shear force values of the YBD loins were higher than the others (p<0.05). The TBARS values of YCY loins were significantly lower than the others at 0 d, but the difference disappeared after 14 d of storage. Sensory scores of YLD were ranked higher than the YCY or YBD in both the loins and bellies (p<0.05). The relatively high sensory values of YLD crossbred pork could be explained by the better WHC, the low shear forces, and the higher fat contents. The results indicated that the meat qualities could be altered by three-way crossbreeding.

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