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1.
Biochem Biophys Res Commun ; 738: 150547, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39178580

RESUMO

Bacteroides fragilis resides in mammals and human intestines and secrete series of proteins and molecules outside that cause various diseases such as colon cancer and chronic colitis in the host. B. fragilis has been shown to produce numerous proteins to the infected cell surface which are involved in host colonization, microbial interactions, and pathogenicity. Among secreted proteins, a B. fragilis toxin (BFT) is a metalloprotease and disintegrates the epithelial cell layer and causes colon cancers. Except the BFT, information of secreted proteases from B. fragilis is limited and no structure is available. Aspartic proteinase cleaves a peptide bond using two aspartate residues in a catalytic site in acidic conditions, pH ranges from 3 to 6. Aspartic proteinase have been characterized mostly from eukaryotes and retroviruses but rare from bacteria including B. fragilis. A putative aspartic proteinase is identified from the B. fragilis genome and prepared recombinantly as a Bacteroides aspartic proteinase (BAPtase). The crystal structure of BAPtase was determined at 2.6 Å. Structure-based comparative and endopeptidase analyses demonstrated that BAPtase presents a two-domain structure and is a functional aspartic proteinase in unusually weak basic pHs, which would propose to be a critical in bacterial pathogenesis and in host immunity. Our observations on the distinct structural and catalytic properties of BAPtase would benefit the future development of B. fragilis-specific drugs or preventatives.

2.
BMC Public Health ; 24(1): 2207, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138446

RESUMO

BACKGROUND: A distinct gap in the literature persists regarding the health outcome of individuals with Type 2 diabetes who also have disabilities. This study aimed to investigate potential disparities in events occurrence among diabetes patients across various disability stages. METHODS: We conducted a retrospective cohort study on patients newly diagnosed with diabetes in 2013 and 2014, aged ≥ 18 years, and followed them until December 2021, using data from the Korean National Health Insurance database. All-cause mortality and hospitalization for diabetes mellitus and cardio-cerebrovascular diseases (CVD) was assessed. RESULTS: The study included 26,085 patients, encompassing individuals without disabilities and those with physical, visual, hearing and speech, intellectual and developmental, and mental disabilities. After adjustment, individuals with disabilities had a higher risk of all-cause death (adjusted hazard ratio [aHR]: 1.25, 95% CI: 1.07-1.48) compared to those without disabilities. In particular, severe disabilities and hearing and speech disabilities showed significantly higher risks of all-cause death (aHR: 1.40, 95% CI: 1.06-1.85 and aHR: 1.58, 95% CI: 1.17-2.15, respectively), with marginal significance for mild disabilities (aHR: 1.20, 95% CI: 0.99-1.45) and mental disorders (aHR: 1.92, 95% CI: 0.98-3.73). Patients with disabilities also had significantly increased risks of CVD-related first admissions (aHR: 1.30, 95% CI: 1.07-1.56) and diabetes-related first admissions (aHR: 1.31, 95% CI: 1.20-1.43) compared to those without disabilities. CONCLUSIONS: This study underscores the urgent need for public health policies to prioritize individuals with disabilities and diabetes, addressing the disparities in health outcome.


Assuntos
Diabetes Mellitus Tipo 2 , Pessoas com Deficiência , Disparidades nos Níveis de Saúde , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/epidemiologia , República da Coreia/epidemiologia , Adulto , Pessoas com Deficiência/estatística & dados numéricos , Idoso , Adulto Jovem , Hospitalização/estatística & dados numéricos , Causas de Morte
3.
BMC Public Health ; 22(1): 1613, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008802

RESUMO

BACKGROUND: Opportunities for paid employment provide meaningful ways for those with disabilities to participate in society and achieve financial independence. Although the onset age of disabilities can alter individuals' attitudes toward accepting their disabilities and their desire for work, the lack of data limits relevant empirical research. The purpose of this study is to examine the effect of the onset age on employment, job security (permanent vs. temporary), and wage level among visually impaired adults in South Korea. METHODS: We used three years of the National Survey on Persons with Disabilities data, 2011, 2014, and 2017, and included 583 participants in this study. We used a logistic regression model for the employment status and a multinomial logistic regression model for job security. We analyzed log monthly wage by a multivariate linear regression model, which subdivided the age groups, with 20-49 years old denoting prime-aged (n = 245) and 50-64 years old denoting late-middle-aged (n = 338). For each age group, we conducted a sub-analysis by sex. RESULTS: For prime-aged adults, the employment probability decreased as the age of visual impartment onset increased, and women in particular experienced a lower employment rate for both permanent and temporary jobs when their disability onset age was above 25. However, among permanent employees, monthly wages were higher if the onset age was 25 + compared to when the onset age was 0-5 years old. In late middle-aged adults, adult onset disabilities were associated with higher odds of employment and higher wages for temporary jobs, implying these individuals worked unskilled or manual jobs. CONCLUSIONS: In prime-aged adults, higher monthly wages among permanent employees showed that they were more likely to continue their original work, whereas in late-middle-aged adults, adult-onset disabilities were associated with a higher employment rate and higher wages for temporary jobs, suggesting the need for further investigation into job quality. These findings indicate a need for differentiated policy approaches considering the onset age of visual impairment to improve labor market outcomes throughout individuals' lifespans.


Assuntos
Pessoas com Deficiência , Emprego , Adulto , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Salários e Benefícios , Transtornos da Visão/epidemiologia , Adulto Jovem
4.
Korean J Parasitol ; 59(5): 489-496, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34724768

RESUMO

Ticks can transmit pathogenic bacteria, protozoa, and viruses to humans and animals. In this study, we investigated the microbiomes of Haemaphysalis longicornis according to sex and life stages. The Shannon index was significantly higher for nymphs than adult ticks. Principal coordinates analysis showed that the microbiome composition of female adult and male adult ticks were different. Notably, Coxiella-like bacterium (AB001519), known as a tick symbiont, was found in all nymphs and female adult ticks, but only one out of 4 male adult ticks had Coxiella-like bacterium (AB001519). In addition, Rickettsia rickettsii, Coxiella burnetii, and Anaplasma bovis were detected in this study.


Assuntos
Ixodidae , Microbiota , Rickettsia , Carrapatos , Anaplasma , Animais , Feminino , Humanos , Masculino , República da Coreia
5.
Biochem Biophys Res Commun ; 532(2): 251-257, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-32868077

RESUMO

Since the first discovery of phenolic acid decarboxylase transcriptional regulator (PadR), its homologs have been identified mostly in bacterial species and constitute the PadR family. PadR family members commonly contain a winged helix-turn-helix (wHTH) motif and function as a transcription factor. However, the PadR family members are varied in terms of molecular size and structure. As a result, they are divided into PadR subfamily-1 and PadR subfamily-2. PadR subfamily-2 proteins have been reported in some pathogenic bacteria, including Listeria monocytogenes and Streptococcus pneumoniae, and implicated in drug resistance processes. Despite the growing numbers of known PadR family proteins and their critical functions in bacteria survival, biochemical and biophysical studies of the PadR subfamily-2 are limited. Here, we report the crystal structure of a PadR subfamily-2 member from Streptococcus pneumoniae (SpPadR) at a 2.40 Å resolution. SpPadR forms a dimer using its N-terminal and C-terminal helices. The two wHTH motifs of a SpPadR dimer expose their positively charged residues presumably to interact with DNA. Our structure-based mutational and biochemical study indicates that SpPadR specifically recognizes a palindromic nucleotide sequence upstream of its encoding region as a transcriptional regulator. Furthermore, comparative structural analysis of diverse PadR family members combined with a modeling study highlights the structural and regulatory features of SpPadR that are canonical to the PadR family or specific to the PadR subfamily-2.


Assuntos
Proteínas de Bactérias/química , Streptococcus pneumoniae/química , Fatores de Transcrição/química , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sequência Conservada , Cristalografia por Raios X , DNA Bacteriano/metabolismo , Polarização de Fluorescência , Modelos Moleculares , Família Multigênica , Mutação , Homologia Estrutural de Proteína , Relação Estrutura-Atividade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Tirosina/genética , Tirosina/metabolismo
6.
Biochem Biophys Res Commun ; 528(1): 85-91, 2020 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-32451086

RESUMO

Pseudomonas aeruginosa is a widely found opportunistic pathogen. The emergence of multidrug-resistant strains and persistent chronic infections have increased. The protein encoded by the pa0423 gene in P. aeruginosa is proposed to be critical for pathogenesis and could be a virulence-promoting protease or a bacterial lipocalin that binds a lipid-like antibiotic for drug resistance. Although two functions of proteolysis and antibiotic resistance are mutually related to bacterial survival in the host, it is very unusual for a single-domain protein to target unrelated ligand molecules such as protein substrates and lipid-like antibiotics. To clearly address the biological role of the PA0423 protein, we performed structural and biochemical studies. We found that PA0423 adopts a single-domain ß-barrel structure and belongs to the lipocalin family. The PA0423 structure houses an internal tubular cavity, which accommodates a ubiquinone-8 molecule. Furthermore, we reveal that PA0423 can directly interact with the polymyxin B antibiotic using the internal cavity, suggesting that PA0423 has a physiological function in the antibiotic resistance of P. aeruginosa.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Pseudomonas aeruginosa/metabolismo , Sequência de Aminoácidos , Cristalografia por Raios X , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Lipocalinas/química , Modelos Moleculares , Polimixina B/química , Polimixina B/metabolismo , Estrutura Secundária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Solubilidade , Homologia Estrutural de Proteína , Ubiquinona/química , Ubiquinona/metabolismo
7.
Health Res Policy Syst ; 18(1): 27, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087709

RESUMO

BACKGROUND: Limited evidence exists on how to assess long-term care system performance. This study aims to report on the process and results of developing a performance assessment framework to evaluate the long-term care system financed by the public long-term care insurance in South Korea. METHODS: The framework was developed through a six-step approach, including setting the goals and scope of performance assessment in the given policy context, reviewing existing performance frameworks, developing a framework with a wide range of potential indicators, refining the framework through a series of Delphi surveys and expert meetings, examining the feasibility of generated indicators through a pilot test, receiving the comments of stakeholders, and finalising the performance framework. RESULTS: The finalised framework has 4 domains - coverage, quality of care, quality of life and system sustainability - and 28 indicators, including 10 core indicators to monitor long-term care system performance. Usability and feasibility along with policy relevance were important criteria in selecting these indicators. The proposed framework can be used to assess the performance of the long-term care system in Korea, and the framework and its methodological approach can be benchmarks for other countries developing their own framework. CONCLUSIONS: It is critical to reconcile and prioritise various stakeholders' views and information needs as well as to balance methodological rigor with practical usefulness and feasibility in the development and implementation of a long-term care performance monitoring system.


Assuntos
Guias como Assunto , Assistência de Longa Duração/estatística & dados numéricos , Assistência de Longa Duração/normas , Política Pública , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde/normas , Humanos , República da Coreia
8.
Int J Geriatr Psychiatry ; 34(3): 472-479, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30478985

RESUMO

OBJECTIVES: Antipsychotics are used to manage the behavioral and psychological symptoms of dementia (BPSD), despite their association with greater risks for mortality and cerebrovascular events. Previous studies in Japan have estimated the prevalence of antipsychotics among older adults who took antidementia drugs. Using long-term care (LTC) data, we aimed to obtain more accurate estimates of the prevalence of antipsychotics and to determine factors related to their use in older adults with dementia. METHODS: Medical and LTC claims data and LTC certification data between April 2012 and September 2013 were obtained from a middle-sized suburban city. The 1-year prevalence of antipsychotic use was estimated among individuals with probable dementia aged greater than or equal to 75 years who were prescribed antidementia drugs and/or had dementia based on LTC needs certification data. RESULTS: Of 25 919 participants, 4865 had probable dementia and 1506 were prescribed antidementia drugs. The prevalence of antipsychotics among participants with probable dementia was 10.7%, which was lower than that in those who were prescribed antidementia drugs (16.4%). Among participants with probable dementia with LTC certification data available (N = 4419), lower cognitive function (vs mild; adjusted odds ratio 2.16, 95% confidence interval 1.63-2.86), antidementia drug use (2.27, 1.84-2.81), and institutional LTC services use (2.34, 1.85-2.97) were associated with greater odds of antipsychotic use, whereas older age (greater than or equal to 92 years) was associated with lower odds (vs less than 77 years; 0.42, 0.27-0.65). CONCLUSIONS: These findings may be useful for estimating the burden of BPSD and for taking measures to reduce inappropriate antipsychotic prescription.


Assuntos
Antipsicóticos/uso terapêutico , Demência/tratamento farmacológico , Uso de Medicamentos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Prescrição Inadequada , Japão/epidemiologia , Assistência de Longa Duração , Masculino , Prevalência
9.
J Epidemiol ; 29(10): 377-383, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30249946

RESUMO

BACKGROUND: This study aimed to determine whether there are disparities in healthcare services utilization according to household income among people aged 75 years or older in Japan. METHODS: We used data on medical and long-term care (LTC) insurance claims and on LTC insurance premiums and needs levels for people aged 75 years or older in a suburban city. Data on people receiving public welfare were not available. Participants were categorized according to household income level using LTC insurance premiums data. The associations of low income with physician visit frequency, length of hospital stay (LOS), and medical and LTC expenditures were evaluated and adjusted for 5-year age groups and LTC needs level. RESULTS: The study analyzed 12,852 men and 18,020 women, among which 13.3% and 41.5%, respectively, were categorized as low income. Participants with low income for both genders were more likely to be functionally dependent. In the adjusted analyses, lower income was associated with fewer physician visits (incidence rate ratio [IRR] 0.90; 95% confidence interval [CI], 0.87-0.92 for men and IRR 0.97; 95% CI, 0.95-0.99 for women), longer LOS (IRR 1.98; 95% CI, 1.54-2.56 and IRR 1.42; 95% CI, 1.20-1.67, respectively), and higher total expenditures (exp(ß) 1.09; 95% CI, 1.01-1.18 and exp(ß) 1.09; 95% CI, 1.05-1.14, respectively). CONCLUSIONS: This study suggests that older people with lower income had fewer consultations with physicians but an increased use of inpatient services. The income categorization used in this study may be an appropriate proxy of socioeconomic status.


Assuntos
Utilização de Instalações e Serviços/estatística & dados numéricos , Custos de Cuidados de Saúde/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Renda , Revisão da Utilização de Seguros/estatística & dados numéricos , Assistência de Longa Duração/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Utilização de Instalações e Serviços/economia , Feminino , Disparidades em Assistência à Saúde , Humanos , Revisão da Utilização de Seguros/economia , Seguro de Assistência de Longo Prazo , Assistência de Longa Duração/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Vigilância da População
10.
BMC Geriatr ; 19(1): 69, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30841859

RESUMO

BACKGROUND: The occurrence of multimorbidity (i.e., the coexistence of multiple chronic diseases) increases with age in older adults and is a growing concern worldwide. Multimorbidity has been reported to be a driving factor in the increase of medical expenditures in OECD countries. However, to the best of our knowledge, there is no published research that has examined the associations between multimorbidity and either long-term care (LTC) expenditure or the sum of medical and LTC expenditures worldwide. We, therefore, aimed to examine the associations of multimorbidity with the sum of medical and LTC expenditures for older adults in Japan. METHODS: Medical insurance claims data for adults ≥75 years were merged with LTC insurance claims data from Kashiwa city, a suburb in the Tokyo metropolitan area, for the period between April 2012 and September 2013 to obtain an estimate of medical and LTC expenditures. We also calculated the 2011 updated and reweighted version of the Charlson Comorbidity Index (CCI) scores. Then, we performed multiple generalized linear regressions to examine the associations of CCI scores (0, 1, 2, 3, 4, or ≥ 5) with the sum of annual medical and LTC expenditures, adjusting for age, sex, and household income level. RESULTS: The mean sum of annual medical and LTC expenditures was ¥1,086,000 (US$12,340; n = 30,042). Medical and LTC expenditures accounted for 66 and 34% of the sum, respectively. Every increase in one unit of the CCI scores was associated with a ¥257,000 (US$2920); 95% Confidence Interval: ¥242,000, 271,000 (US$2750, 3080) increase in the sum of the expenditures (p < 0.001; n = 29,915). CONCLUSIONS: Using a merged medical and LTC claims dataset, we found that greater CCI scores were associated with a higher sum of annual medical and LTC expenditures for older adults. To the best of our knowledge, this is the first study to examine the associations of multimorbidity with LTC expenditures or the sum of medical and LTC expenditures worldwide. Our study indicated that the economic burden on society caused by multimorbidity could be better evaluated by the sum of medical and LTC expenditures, rather than medical expenditures alone.


Assuntos
Geriatria , Gastos em Saúde/estatística & dados numéricos , Seguro de Assistência de Longo Prazo/economia , Assistência de Longa Duração/economia , Multimorbidade/tendências , Idoso , Idoso de 80 Anos ou mais , Feminino , Geriatria/economia , Inquéritos Epidemiológicos , Humanos , Japão/epidemiologia , Masculino
11.
Biochem Biophys Res Commun ; 487(2): 381-387, 2017 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-28414127

RESUMO

FliS is a cytoplasmic flagellar chaperone for the flagellin, which polymerizes into filaments outside of the flagellated bacteria. Cytoplasmic interaction between FliS and flagellin is critical to retain the flagellin protein in a monomeric form, which is transported from the cytoplasm through the flagellar export apparatus to the extracellular space for filament assembly. Defects in the FliS protein directly diminish bacterial motility, pathogenicity, and viability. Although the overall structure of FliS is known, structural and mutational studies on FliS from other bacterial species are still required to reveal any unresolved biophysical features of FliS itself or functionally critical residues for flagellin recognition. Here, we present the crystal structure of FliS from Bacillus cereus (BcFliS) at 2.0 Å resolution. FliS possesses a highly dynamic N-terminal region, which is appended to the common four-helix bundle structure. An invariant proline residue (Pro17 in B. cereus FliS) was identified in all known FliS sequences between the N-terminal region and the four-helix bundle. The N-terminal proline residue functions as a helix breaker critical for FliS dimerization and flagellin recognition.


Assuntos
Bacillus cereus/metabolismo , Proteínas de Bactérias/ultraestrutura , Flagelos/metabolismo , Flagelina/química , Flagelina/ultraestrutura , Prolina/química , Sítios de Ligação , Modelos Químicos , Chaperonas Moleculares/química , Simulação de Acoplamento Molecular , Ligação Proteica , Conformação Proteica , Multimerização Proteica , Relação Estrutura-Atividade
12.
Malar J ; 16(1): 3, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-28049479

RESUMO

BACKGROUND: Glutamate dehydrogenase of malaria parasites (pGDH) is widely used in rapid diagnostic tests for malaria. Variation in the pGDH gene among Korean isolates of Plasmodium vivax was analysed, and a recombinant pGDH protein was evaluated for use as antigens for the serodiagnosis of vivax malaria. METHODS: Genomic DNA was purified from blood samples of 20 patients and the pGDH gene of P. vivax was sequenced. Recombinant protein was prepared to determine the antigenicity of pGDH by enzyme-linked immunosorbent assay (ELISA). RESULTS: Partial sequence analysis of the P. vivax pGDH gene from the 20 Korean isolates showed that an open reading frame (ORF) of 1410 nucleotides encoded a deduced protein of 470 amino acids. The amino acid and nucleotide sequences were conserved among all the Korean isolates. This ORF showed 100% homology with P. vivax strain Sal-I (GenBank accession No. XP_001616617.1). The full ORF (amino acids 39-503), excluding the region before the intron, was cloned from isolate P. vivax Bucheon 3 (KJ726751) and subcloned into the expression vector pET28b for transformation into Escherichia coli BL21(DE3)pLysS. The expressed recombinant protein had a molecular mass of approximately 55 kDa and showed 84.8% sensitivity (39/46 cases) and 97.2% specificity (35/36 cases) in an ELISA. The efficacy of recombinant pGDH protein in seroepidemiological studies was also evaluated by ELISA using serum samples collected from 876 inhabitants of Gyodong-myeon, Ganghwa County, Incheon Metropolitan City. Of these samples, 91 (10.39%) showed a positive reaction with recombinant pGDH protein. Among the antibody-positive individuals, 13 (14.29%) had experienced malaria infection during the last 10 years. CONCLUSION: The pGDH genes of P. vivax isolates from representative epidemic-prone areas of South Korea are highly conserved. Therefore, pGDH is expected to be a useful antigen in seroepidemiological studies. It was difficult to identify the foci of malaria transmission in Gyodong-myeon based on the patient distribution because of the very low parasitaemia of Korean vivax malaria. However, seroepidemiology with recombinant pGDH protein easily identified regions with the highest incidence of malaria within the study area. Therefore, recombinant pGDH protein may have a useful role in serodiagnosis.


Assuntos
Variação Genética , Glutamato Desidrogenase/genética , Malária Vivax/diagnóstico , Plasmodium vivax/enzimologia , Testes Sorológicos/métodos , Sequência Conservada , DNA de Protozoário/química , DNA de Protozoário/genética , DNA de Protozoário/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/métodos , Escherichia coli , Humanos , Plasmodium vivax/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , República da Coreia , Análise de Sequência de DNA
13.
Korean J Parasitol ; 55(3): 357-361, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28719964

RESUMO

During civil engineering construction near Sejong-ro, Jongro-ku, Seoul, cultural sites were found that are thought to have been built in the 15th century. This area was home to many different people as well as the leaders of the Yi dynasty. To gain further insight into the life styles of the inhabitants of the old capital, soil samples were collected from various areas such as toilets, water foundations, and drainage ways. Parasite eggs were examined by microscopy after 5 g soil samples were rehydrated in 0.5% trisodium phosphate solution. A total of 662 parasite eggs from 7 species were found. Species with the highest number of eggs found were Ascaris lumbricoides (n=483), followed by Trichuris trichiura (138), Trichuris vulpis (21), Fasciola hepatica (8), Clonorchis sinensis (6), Paragonimus westermani (4), and Metagonimus yokogawai (2). These findings indirectly indicate the food habits of the people in Yi dynasty.


Assuntos
Arqueologia , Comportamento Alimentar , Estilo de Vida/história , Contagem de Ovos de Parasitas , Parasitologia , Solo/parasitologia , Animais , Ascaris lumbricoides , Clonorchis sinensis , Fasciola hepatica , Heterophyidae , História do Século XV , Humanos , Paragonimus westermani , República da Coreia , Trichuris
14.
Korean J Parasitol ; 55(4): 451-455, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28877580

RESUMO

Echinostoma cinetorchis is an oriental intestinal fluke causing significant pathological damage to the small intestine. The aim of this study was to determine a full-length cDNA sequence of E. cinetorchis endoribonuclease (RNase H; EcRNH) and to elucidate its molecular biological characters. EcRNH consisted of 308 amino acids and showed low similarity to endoribonucleases of other parasites (<40%). EcRNH had an active site centered on a putative DDEED motif instead of DEDD conserved in other species. A recombinant EcRNH produced as a soluble form in Escherichia coli showed enzymatic activity to cleave the 3'-O-P bond of RNA in a DNA-RNA duplex, producing 3'-hydroxyl and 5'-phosphate. These findings may contribute to develop antisense oligonucleotides which could damage echinostomes and other flukes.


Assuntos
Sequência de Bases/genética , DNA de Helmintos/genética , Echinostoma/enzimologia , Ribonuclease H/genética , Sequência de Aminoácidos , Animais , Oligonucleotídeos Antissenso , Ribonuclease H/química , Análise de Sequência de DNA
15.
Infect Immun ; 82(1): 132-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24126533

RESUMO

Despite the generation of Mycobacterium tuberculosis-specific T cell immune responses during the course of infection, only 5 to 10% of exposed individuals develop active disease, while others develop a latent infection. This phenomenon suggests defective M. tuberculosis-specific immunity, which necessitates more careful characterization of M. tuberculosis-specific T cell responses. Here, we longitudinally analyzed the phenotypes and functions of M. tuberculosis-specific T cells. In contrast to the functional exhaustion of T cells observed after chronic infection, M. tuberculosis-specific CD8(+) T cells differentiated into either effector (CD127(lo) CD62L(lo)) or effector memory (CD127(hi) CD62L(lo)) cells, but not central memory cells (CD127(hi) CD62L(hi)), with low programmed death 1 (PD-1) expression, even in the presence of high levels of bacteria. Additionally, M. tuberculosis-specific CD8(+) and CD4(+) T cells produced substantial levels of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), but not interleukin 2 (IL-2), upon in vitro restimulation. Among M. tuberculosis-specific CD8(+) T cells, CD127(hi) effector memory cells displayed slower ongoing turnover but greater survival potential. In addition, these cells produced more IFN-γ and TNF-α and displayed lytic activity upon antigen stimulation. However, the effector function of M. tuberculosis-specific CD8(+) CD127(hi) effector memory T cells was inferior to that of canonical CD8(+) CD127(hi) memory T cells generated after acute lymphocytic choriomeningitis virus infection. Collectively, our data demonstrate that M. tuberculosis-specific T cells can differentiate into memory T cells during the course of M. tuberculosis infection independent of the bacterial burden but with limited functionality. These results provide a framework for further understanding the mechanisms of M. tuberculosis infection that can be used to develop more effective vaccines.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Animais , Antígenos de Bactérias/imunologia , Antígenos de Diferenciação/imunologia , Carga Bacteriana , Diferenciação Celular/imunologia , Doença Crônica , Modelos Animais de Doenças , Feminino , Imunidade Celular/imunologia , Memória Imunológica/fisiologia , Interferon gama/metabolismo , Estudos Longitudinais , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Linfócitos T Auxiliares-Indutores/imunologia , Fator de Necrose Tumoral alfa/metabolismo
16.
PLoS Pathog ; 8(4): e1002614, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22496642

RESUMO

Trehalose 6,6'-dimycolate (TDM), a cord factor of Mycobacterium tuberculosis (Mtb), is an important regulator of immune responses during Mtb infections. Macrophages recognize TDM through the Mincle receptor and initiate TDM-induced inflammatory responses, leading to lung granuloma formation. Although various immune cells are recruited to lung granulomas, the roles of other immune cells, especially during the initial process of TDM-induced inflammation, are not clear. In this study, Mincle signaling on neutrophils played an important role in TDM-induced lung inflammation by promoting adhesion and innate immune responses. Neutrophils were recruited during the early stage of lung inflammation following TDM-induced granuloma formation. Mincle expression on neutrophils was required for infiltration of TDM-challenged sites in a granuloma model induced by TDM-coated-beads. TDM-induced Mincle signaling on neutrophils increased cell adherence by enhancing F-actin polymerization and CD11b/CD18 surface expression. The TDM-induced effects were dependent on Src, Syk, and MAPK/ERK kinases (MEK). Moreover, coactivation of the Mincle and TLR2 pathways by TDM and Pam3CSK4 treatment synergistically induced CD11b/CD18 surface expression, reactive oxygen species, and TNFα production by neutrophils. These synergistically-enhanced immune responses correlated with the degree of Mincle expression on neutrophil surfaces. The physiological relevance of the Mincle-mediated anti-TDM immune response was confirmed by defective immune responses in Mincle⁻/⁻ mice upon aerosol infections with Mtb. Mincle-mutant mice had higher inflammation levels and mycobacterial loads than WT mice. Neutrophil depletion with anti-Ly6G antibody caused a reduction in IL-6 and monocyte chemotactic protein-1 expression upon TDM treatment, and reduced levels of immune cell recruitment during the initial stage of infection. These findings suggest a new role of Mincle signaling on neutrophils during anti-mycobacterial responses.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Fatores Corda/efeitos adversos , Lectinas Tipo C/metabolismo , Proteínas de Membrana/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Animais , Antígeno CD11b/genética , Antígeno CD11b/imunologia , Antígeno CD11b/metabolismo , Antígenos CD18/genética , Antígenos CD18/imunologia , Antígenos CD18/metabolismo , Fatores Corda/química , Fatores Corda/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Granuloma do Sistema Respiratório/induzido quimicamente , Granuloma do Sistema Respiratório/genética , Granuloma do Sistema Respiratório/imunologia , Granuloma do Sistema Respiratório/metabolismo , Granuloma do Sistema Respiratório/patologia , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Camundongos Knockout , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/metabolismo , Infiltração de Neutrófilos/genética , Infiltração de Neutrófilos/imunologia , Neutrófilos/imunologia , Neutrófilos/patologia , Pneumonia/genética , Pneumonia/imunologia , Pneumonia/patologia , Proteínas Quinases/genética , Proteínas Quinases/imunologia , Proteínas Quinases/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/imunologia , Receptor 2 Toll-Like/metabolismo , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/metabolismo , Tuberculose Pulmonar/patologia
17.
Biosci Biotechnol Biochem ; 78(3): 503-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25036842

RESUMO

A conventional fermenter (CF), a single-cathode fermenter (SCF), and a double-cathode fermenter (DCF) were employed to evaluate and compare the effects of H2 and electrochemical reducing power on metabolite production by Clostridium acetobutylicum KCTC1037. The source of the external reducing power for CF was H2, for the SCF was electrochemically reduced neutral red-modified graphite felt electrode (NR-GF), and for the DCF was electrochemically reduced combination of NR-GF and platinum plate electrodes (NR-GF/PtP). The metabolites produced from glucose or CO2 by strain KCTC1037 cultivated in the DCF were butyrate, ethanol, and butanol, but ethanol and butanol were not produced from glucose or CO2 by strain KCTC1037 cultivated in the CF and SCF. It is possible that electrochemically reduced NR-GF/PtP is a more effective source of internal and external reducing power than H2 or NR-GF for strain KCTC1037 to produce metabolites from glucose and CO2. This research might prove useful in developing fermentation technology to actualize direct bioalcohol production of fermentation bacteria from CO2.


Assuntos
Reatores Biológicos , Clostridium acetobutylicum/química , Fermentação , Butanóis/química , Butiratos/química , Dióxido de Carbono/química , Dióxido de Carbono/metabolismo , Clostridium acetobutylicum/crescimento & desenvolvimento , Eletrodos , Etanol/química , Glucose/química , Glucose/metabolismo
18.
Disabil Health J ; 17(3): 101613, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38514295

RESUMO

BACKGROUND: Visual disabilities (VD) are expected to rise with an aging population. Persons with VD experience a higher prevalence of chronic and acute diseases. Despite the significance of influenza to this population, there is limited data comparing influenza care disparities between those with VD and those without. OBJECTIVE: The study aimed to determine the influenza burden and associated healthcare utilization in individuals with VD compared to those without disabilities. METHODS: A retrospective cohort study was conducted using the Korean National Health Information Database, encompassing three influenza seasons (2011-2012 to 2013-2014). The influenza incidence and incidence rate ratio (IRR) was calculated. Adjusted IRRs were calculated using a zero-inflated Poisson model. We assessed the risk of admissions and 30-day post-influenza mortality, employing logistic regression or survival analysis. RESULTS: A total of 504,374 patients (252,964 patients with VD and 251,410 controls) were followed for 1,471,480 person-years. The influenza incidence was higher in the VD cohort than in the control (8.8 vs. 7.8 cases per 1000 person-years). VD cohort had a higher influenza IRR (adjusted IRR 1·13, 95% confidence interval [CI] 1·02-1·25). Severe VD exhibited higher hospitalization risk (adjusted odds ratio [OR] 1·29, 95% CI 1·10-1·20) and increased medical costs. Severe VD was a significant risk factor for mortality (adjusted Hazard Ratio 1·89, 95% CI 1·04-3·45). CONCLUSIONS: People with VD have a higher influenza incidence, while their outcomes are comparable to those without. Nevertheless, severe VD significantly contributes more to hospitalization, mortality, and medical costs than controls.


Assuntos
Pessoas com Deficiência , Hospitalização , Influenza Humana , Transtornos da Visão , Humanos , Influenza Humana/epidemiologia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Incidência , Adulto , Idoso , República da Coreia/epidemiologia , Pessoas com Deficiência/estatística & dados numéricos , Transtornos da Visão/epidemiologia , Fatores de Risco , Adulto Jovem , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Modelos Logísticos , Estudos de Coortes , Bases de Dados Factuais , Idoso de 80 Anos ou mais , Razão de Chances
19.
J Clin Microbiol ; 51(5): 1451-7, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23447637

RESUMO

Rapid and accurate identification of the pathogens involved in bloodstream infections is crucial for the prompt initiation of appropriate therapy, as this can decrease morbidity and mortality rates. A PCR-reverse blot hybridization assay for sepsis, the reverse blot hybridization assay (REBA) Sepsis-ID test, was developed; it uses pan-probes to distinguish Gram-positive and -negative bacteria and fungi. In addition, the assay was designed to identify bacteria and fungi using six genus-specific and 13 species-specific probes; it uses additional probes for antibiotic resistance genes, i.e., the mecA gene of methicillin-resistant Staphylococcus aureus (MRSA) and the vanA and vanB genes of vancomycin-resistant enterococci (VRE). The REBA Sepsis-ID test successfully identified clinical isolates and blood culture samples as containing Gram-positive bacteria, Gram-negative bacteria, or fungi. The results matched those obtained with conventional microbiological methods. For the REBA Sepsis-ID test, of the 115 blood culture samples tested, 47 (40.8%) and 49 (42.6%) samples were identified to the species and genus levels, respectively, and the remaining 19 samples (16.5%), which included five Gram-positive rods, were identified as Gram-positive bacteria, Gram-negative bacteria, or fungi. The antibiotic resistances of the MRSA and VRE strains were identified using both conventional microbiological methods and the REBA Sepsis-ID test. In conclusion, the REBA Sepsis-ID test developed for this study is a fast and reliable test for the identification of Gram-positive bacteria, Gram-negative bacteria, fungi, and antibiotic resistance genes (including mecA for MRSA and the vanA and vanB genes for VRE) in bloodstream infections.


Assuntos
Bactérias , Infecções Bacterianas/diagnóstico , Fungos , Micoses/diagnóstico , Sepse/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Proteínas de Bactérias/genética , Carbono-Oxigênio Ligases/genética , Farmacorresistência Bacteriana Múltipla/genética , Fungos/classificação , Fungos/genética , Fungos/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas , Reação em Cadeia da Polimerase , Kit de Reagentes para Diagnóstico , Sepse/diagnóstico
20.
Int J Public Health ; 68: 1605312, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36926283

RESUMO

Objectives: This study examines the inequality between people with and without disabilities regarding unmet healthcare needs and preventable hospitalization. Methods: We used the Korea Health Panel of 2016-2018; the final analytical observations were 43,512, including 6.95% of persons with disabilities. We examined the differences in contributors to the two dependent variables and decomposed the observed differences into explained and unexplained components using the Oaxaca-Blinder approach. Results: Unmet healthcare needs and preventable hospitalizations were 5.6% p (15.36% vs. 9.76%) and 0.68% p (1.82% vs. 0.61%), respectively, higher in people with disabilities than in those without, of which 48% and 35% were due to characteristics that the individual variables cannot explain. Decomposition of the distributional effect showed that sex, age, and chronic disease significantly increased disparities for unmet healthcare needs and preventable hospitalization. Socioeconomic factors such as income level and Medical aid significantly increased the disabled-non-disabled disparities for unmet healthcare needs. Conclusion: Socioeconomic conditions increased the disparities, but around 35%-48% of the disparities in unmet healthcare needs and preventable hospitalization were due to unexplained factors, such as environmental barriers.


Assuntos
Pessoas com Deficiência , Necessidades e Demandas de Serviços de Saúde , Humanos , Disparidades em Assistência à Saúde , Fatores Socioeconômicos , Hospitalização , República da Coreia/epidemiologia
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