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1.
Clin Exp Hypertens ; 45(1): 2236336, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37503669

RESUMO

The prognosis of dialysis patients is poorer than that of the general population. The relationship between dialysis patients' blood pressure (BP) and mortality is controversial. We investigated the relationships between mortality and (i) pre-dialysis BP and (ii) BP variation during hemodialysis in maintenance dialysis patients.We retroactively analyzed the cases of the 284 patients on hemodialysis (mean age 68 ± 13 years old) who had been regularly followed at Kokura Daiichi Hospital, Japan in 2018. We assessed the relationship between the patients' BP components and risk of mortality over a 40-month follow-up.The patients' average systolic/diastolic BP values before dialysis in 2018 were 145 ± 18/77 ± 11, and those after dialysis were 129 ± 17/71 ± 10 mmHg. The prevalence of intradialytic hypotension was 46.8%. During an average follow-up of 35 months, 72 patients died, including from infectious diseases (n = 41), cardiovascular diseases (n = 9), malignancies (n = 5), and others (n = 17). The mortality rate was 32.7% in the pre-dialysis SBP < 140 mmHg group, 20.6% in the 140-159 mmHg group, and 22.2% in ≥ 160 mmHg group. In a multivariable-adjusted analysis, the hazard ratio for mortality in the pre-dialysis SBP < 140 mmHg group with intradialytic hypotension was significantly higher than that in the 140-159 mmHg group.In dialysis patients, pre-dialysis SBP < 140 mmHg and intradialytic hypotension posed a significantly higher risk for mortality. Our findings suggest that not only lower pre-dialysis BP, but also intradialytic hypotension is associated with poor prognosis in dialysis patients.


Assuntos
Hipotensão , Falência Renal Crônica , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/fisiologia , Diálise , Diálise Renal/efeitos adversos , Hipotensão/epidemiologia , Hipotensão/etiologia , Prognóstico , Falência Renal Crônica/terapia
2.
Respiration ; 101(4): 345-352, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34784604

RESUMO

BACKGROUND: The vertical P-wave axis on electrocardiography (ECG) is a useful criterion for screening patients with chronic obstructive pulmonary disease (COPD). This study aimed to investigate the clinical characteristics of patients with COPD with a vertical P-wave axis as they have not yet been elucidated. METHODS: Keio University and its affiliated hospitals conducted an observational COPD cohort study over 3 years. We analyzed 201 patients using ECG and chest computed tomography. RESULTS: The severity of airflow limitation was higher in patients with a P-wave axis >75° than in those with a P-wave axis ≤75°. Patients with a P-wave axis >75° exhibited significantly higher total COPD assessment test scores and increased St. George's Respiratory Questionnaire total, activity, and impact scores than those with a P-wave axis ≤75°. The incidence of exacerbations over 1 and 3 years was significantly higher in patients with a P-wave axis >75° than in those with a P-wave axis ≤75°. The optimal cutoff for the P-wave axis for a percentage of the predicted forced expiratory volume in 1 s <50% and future exacerbations over 3 years was 70° (the areas under the curve [AUC]: 0.788; sensitivity: 65.3%; specificity: 78.3%) and 79° (AUC: 0.642; sensitivity: 36.7%; specificity: 92.6%). The ratio of the low attenuation area was also significantly higher in patients with a P-wave axis >75° than in those with a P-wave axis ≤75°. However, the ratio of the airway wall area did not differ between the 2 groups. CONCLUSIONS: Patients with COPD with a vertical P-wave axis exhibited severe airflow limitation and emphysema, a worse health status, and more frequent exacerbation than patients without a vertical P-wave. Detection of the vertical P-wave axis by ECG is beneficial for the management of patients with COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Estudos de Coortes , Eletrocardiografia , Volume Expiratório Forçado , Humanos , Enfisema Pulmonar/diagnóstico
3.
Respir Res ; 22(1): 18, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33451329

RESUMO

BACKGROUND: Physical inactivity due to cachexia and muscle wasting is well recognized as a sign of poor prognosis in chronic obstructive pulmonary disease (COPD). However, there have been no reports on the relationship between trunk muscle measurements and energy expenditure parameters, such as the total energy expenditure (TEE) and physical activity level (PAL), in COPD. In this study, we investigated the associations of computed tomography (CT)-derived muscle area and density measurements with clinical parameters, including TEE and PAL, in patients with or at risk for COPD, and examined whether these muscle measurements serve as an indicator of TEE and PAL. METHODS: The study population consisted of 36 male patients with (n = 28, stage 1-4) and at risk for (n = 8) COPD aged over 50 years. TEE was measured by the doubly labeled water method, and PAL was calculated as the TEE/basal metabolic rate estimated by the indirect method. The cross-sectional areas and densities of the pectoralis muscles, rectus abdominis muscles, and erector spinae muscles were measured. We evaluated the relationship between these muscle measurements and clinical outcomes, including body composition, lung function, muscle strength, TEE, and PAL. RESULTS: All the muscle areas were significantly associated with TEE, severity of emphysema, and body composition indices such as body mass index, fat-free mass, and trunk muscle mass. All trunk muscle densities were correlated with PAL. The product of the rectus abdominis muscle area and density showed the highest association with TEE (r = 0.732) and PAL (r = 0.578). Several trunk muscle measurements showed significant correlations with maximal inspiratory and expiratory pressures, indicating their roles in respiration. CONCLUSIONS: CT-derived measurements for trunk muscles are helpful in evaluating physical status and function in patients with or at risk for COPD. Particularly, trunk muscle evaluation may be a useful marker reflecting TEE and PAL.


Assuntos
Metabolismo Energético/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Exercício Físico/fisiologia , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Risco
4.
Clin Exp Nephrol ; 25(12): 1354-1359, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34224007

RESUMO

BACKGROUND: The prevalence of sleep disordered breathing is high in patients with end-stage renal disease. Salt intake is related to the severity of obstructive sleep apnea in patients with resistant hypertension and hyperaldosteronism. We investigated the relationship between salt intake and sleep disordered breathing in patients on maintenance hemodialysis. PATIENTS AND METHODS: We studied 128 dialysis outpatients (mean age 63 ± 11 years) who were followed at Kokura Daiichi Hospital. We estimated each patient's salt intake using an InBody S10 body composition analyzer and measured the 3% oxygen desaturation index (ODI) during sleep using a Pulsewatch: PMP-200 GplusX. RESULTS: The average estimated salt intake was 8.0 ± 2.6 g/day, and the median value of that was 7.5 g/day. Blood pressure (BP) before and after dialysis were 140 ± 18/78 ± 11 and 127 ± 13/72 ± 8 mmHg, respectively. The geometric average number of 3% ODI was 7.1, and sleep disordered breathing was detected in 30% of all subjects. The patients with ≥ 7.5 g/day salt intake were younger and more frequently male and had higher body mass index (BMI) and BP before dialysis compared to those with salt intakes < 7.5 g/day. Patients with ≥ 7.5 g/day salt intake had a significantly higher geometric average number of 3% ODI; however, this relationship became weaker after adjusting for BMI. The same relationship was obtained for the prevalence of sleep disordered breathing. CONCLUSION: The prevalence of sleep disordered breathing in patients on maintenance hemodialysis was high, and the sleep disordered breathing was associated with salt intake and BMI.


Assuntos
Nefropatias/terapia , Diálise Renal , Síndromes da Apneia do Sono/epidemiologia , Cloreto de Sódio na Dieta/efeitos adversos , Idoso , Índice de Massa Corporal , Feminino , Humanos , Japão/epidemiologia , Nefropatias/diagnóstico , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Prevalência , Diálise Renal/efeitos adversos , Medição de Risco , Fatores de Risco , Síndromes da Apneia do Sono/diagnóstico
5.
Arerugi ; 70(1): 33-38, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33597344

RESUMO

Although an important cause of vocal cord dysfunction (VCD) is psychogenic reaction, VCD may be associated with severe asthma and must be distinguished from the disease. A 30-years-old woman was admitted to our hospital with dyspnea despite treatment for asthma. Inspiratory stridor and expiratory wheezes were noted, and neck and chest computed tomography showed normal airways and lungs. Fractional exhaled nitric oxide levels were also normal. Pulmonary function test with a flow-volume loop curve showed normal expiratory loop with flattening of the inspiratory loop after methacholine inhalation. During the attack, bronchoscopy revealed the vocal cord closing with stridor during the inspiratory phase. Therefore, the patient was diagnosed with VCD. The dyspnea improved with respiratory rehabilitation and pursed-lip breathing. VCD should be considered in the differential diagnosis of intractable severe asthma. In this case, bronchoscopy and bronchial inhalation challenge with methacholine helped in the diagnosis.


Assuntos
Asma , Disfunção da Prega Vocal , Adulto , Asma/diagnóstico , Testes de Provocação Brônquica , Broncoscopia , Diagnóstico Diferencial , Feminino , Humanos , Disfunção da Prega Vocal/diagnóstico , Disfunção da Prega Vocal/etiologia , Prega Vocal
6.
Appl Environ Microbiol ; 85(3)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30478227

RESUMO

Filamentous fungi are used for food fermentation and industrial production of recombinant proteins. They also serve as a source of secondary metabolites and are recently expected as hosts for heterologous production of useful secondary metabolites. Multiple-step genetic engineering is required to enhance industrial production involving these fungi, but traditional sequential modification of multiple genes using a limited number of selection markers is laborious. Moreover, efficient genetic engineering techniques for industrial strains have not yet been established. We have previously developed a clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9-based mutagenesis technique for the industrial filamentous fungus Aspergillus oryzae, enabling mutation efficiency of 10 to 20%. Here, we improved the CRISPR/Cas9 approach by including an AMA1-based autonomously replicating plasmid harboring the drug resistance marker ptrA By using the improved mutagenesis technique, we successfully modified A. oryzae wild and industrial strains, with a mutation efficiency of 50 to 100%. Conditional expression of the Aoace2 gene from the AMA1-based plasmid severely inhibited fungal growth. This enabled forced recycling of the plasmid, allowing repeated genome editing. Further, double mutant strains were successfully obtained with high efficiency by expressing two guide RNA molecules from the genome-editing plasmid. Cotransformation of fungal cells with the genome-editing plasmid together with a circular donor DNA enabled marker-free multiplex gene deletion/integration in A. oryzae The presented repeatable marker-free genetic engineering approach for mutagenesis and gene deletion/integration will allow for efficient modification of multiple genes in industrial fungal strains, increasing their applicability.IMPORTANCE Multiple gene modifications of specific fungal strains are required for achieving industrial-scale production of enzymes and secondary metabolites. In the present study, we developed an efficient multiple genetic engineering technique for the filamentous fungus Aspergillus oryzae The approach is based on a clustered regulatory interspaced short palindromic repeats (CRISPR)/Cas9 system and recycling of an AMA1-based autonomous replicating plasmid. Because the plasmid harbors a drug resistance marker (ptrA), the approach does not require the construction of auxotrophic industrial strains prior to genome editing and allows for forced recycling of the gene-editing plasmid. The established plasmid-recycling technique involves an Aoace2-conditional expression cassette, whose induction severely impairs fungal growth. We used the developed genetic engineering techniques for highly efficient marker-free multiple gene deletion/integration in A. oryzae The genome-editing approaches established in the present study, which enable unlimited repeatable genetic engineering, will facilitate multiple gene modification of industrially important fungal strains.


Assuntos
Aspergillus oryzae/genética , Aspergillus oryzae/metabolismo , Sistemas CRISPR-Cas , Deleção de Genes , Edição de Genes , Engenharia Genética , Genoma Fúngico , Microbiologia Industrial , Mutagênese , Plasmídeos/genética , Plasmídeos/metabolismo
7.
Biomarkers ; 23(5): 414-421, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29376431

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation with endothelial dysfunction. Cadherins are adhesion molecules on epithelial (E-) and vascular endothelial (VE-) cells. Soluble (s) cadherin is released from the cell surface by the effects of proteases including matrix metalloproteinases (MMPs). OBJECTIVE: The aim of this study was to examine the associations of sE-/sVE-cadherin levels in plasma with the development of COPD. METHODS: Plasma sE-/VE-cadherin levels were measured by an enzyme-linked immunosorbent assay in 115 patients with COPD, 36 symptomatic smokers (SS), 63 healthy smokers (HS) and 78 healthy non-smokers (HN). sE-cadherin and MMP-7 levels in epithelial lining fluid (ELF) were measured in 24 patients (12 COPD and 12 control). RESULTS: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios were significantly higher in COPD and SS than in HS and HN groups, while plasma sVE-cadherin levels were lower in COPD than in HS and HN groups (p < 0.0001). sE-cadherin levels paralleled the severity of airflow limitation in both plasma (p < 0.01) and ELF (p < 0.05), while plasma sVE-cadherin levels were inversely correlated with the extent of emphysema (p < 0.05). MMP-7 levels were correlated with sE-cadherin levels in ELF. CONCLUSIONS: Plasma sE-cadherin levels and sE-cadherin/sVE-cadherin ratios are potential biomarkers for COPD.


Assuntos
Caderinas/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Idoso , Antígenos CD , Biomarcadores/sangue , Estudos de Casos e Controles , Enfisema/sangue , Feminino , Humanos , Masculino , Metaloproteinase 7 da Matriz/sangue , Pessoa de Meia-Idade , Fumantes , Solubilidade
8.
J Clin Periodontol ; 45(1): 38-45, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28985442

RESUMO

AIM: To evaluate the association between periodontal disease and pneumonia mortality in haemodialysis patients. MATERIALS AND METHODS: This prospective cohort study included 211 patients (mean age, 64.4 years) undergoing haemodialysis at a single medical centre. The patients underwent a baseline clinical dental examination in 2008 and were then followed up until July 2015. Periodontal disease was defined as the presence of clinical attachment loss of ≥4 mm in ≥30% of the probed sites. The primary endpoint, that is death from pneumonia, was determined by reviewing death certificates and was analysed using the competing-risks regression model. RESULTS: At baseline, 92 patients (43.6%) had periodontal disease. The median follow-up period was 84 months (interquartile range, 36-86 months). Of the 68 deaths that occurred, 21 were from pneumonia. The multivariable competing-risks regression model showed that periodontal disease was significantly associated with death from pneumonia (adjusted subhazard ratio, 3.49; 95% confidence interval, 1.14-10.64), after adjusting for other baseline health characteristics. CONCLUSIONS: The results of this study suggest that periodontal disease is independently associated with pneumonia mortality in haemodialysis patients. Future studies evaluating the potential effect of oral interventions for periodontal health improvement on pneumonia in haemodialysis patients would be of great interest.


Assuntos
Doenças Periodontais/mortalidade , Pneumonia Bacteriana/mortalidade , Diálise Renal , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Periodontais/complicações , Pneumonia Bacteriana/complicações , Medição de Risco , Fatores de Tempo
9.
BMC Pulm Med ; 18(1): 65, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29720140

RESUMO

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a biomarker of inflammation in chronic obstructive pulmonary disease (COPD) patients. But, a meaningful threshold and the longitudinal changes are unknown. We aimed to investigate the association between NLR and the clinical characteristics of COPD patients and to determine a meaningful threshold and the longitudinal changes for NLR. METHODS: Keio University and its affiliate hospitals conducted an observational COPD cohort study over 3 years. We performed a blood examination and a pulmonary function test. Blood examination was completed at baseline and annually thereafter, at a time when the disease was stable. Two hundred seventy-four patients who had at least 3 blood examinations over 3 years were included. RESULTS: Baseline NLR was correlated with baseline C-reactive protein (CRP) (r = 0.18, p = 0.003) and SAA (r = 0.34, p <  0.001). We defined an NLR score of 2.7 as the arbitrary cut-off value based on upper quartile points. COPD patients with NLR ≥ 2.7 were older (p = 0.037), had a lower BMI (p = 0.005) and a lower %FEV1 (p = 0.0003) compared to patients with NLR < 2.7. Receiver-operating-characteristic (ROC) curves showed the optimal cutoff for the baseline NLR in the predicting moderate/severe exacerbation to be 2.7, which was same as the upper quartile points. Follow-up analysis over 3 years revealed that the differences in the trends of NLR among the three groups based on the categories of exacerbations (moderate or severe, mild, no exacerbation) were significant (p = 0.006). CONCLUSIONS: NLR is associated with COPD severity and exacerbations. For predicting exacerbations, we estimated the threshold of NLR to be 2.7 at baseline. TRIAL REGISTRATION: Clinical trial registered with the University Hospital Medication Information Network ( UMIN000003470 , April 10, 2010).


Assuntos
Contagem de Leucócitos/métodos , Linfócitos , Neutrófilos , Doença Pulmonar Obstrutiva Crônica , Testes de Função Respiratória/métodos , Adulto , Idoso , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Exacerbação dos Sintomas
10.
Chron Respir Dis ; 15(4): 329-338, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29232989

RESUMO

Cigarette smoking increases the risk of developing both cataract and chronic obstructive pulmonary disease (COPD). The prevalence of cataract and the clinical characteristics of COPD patients with cataract were retrospectively investigated in a 2-year observational COPD cohort. We analyzed 395 patients with complete data on ophthalmologic evaluation (319 subjects with COPD and 76 subjects at risk of COPD). There was no difference in the prevalence of cataract between COPD patients and those at risk (47.0% vs. 42.1%, p = 0.44). Age ≥ 75 years, low body mass index, and hypertension were independently associated with cataract as a comorbidity in COPD. The incidence of exacerbation within 2 years was significantly higher in COPD patients with cataract than those without cataract (36.6% vs. 18.3%, p = 0.0019). COPD patients with cataract exhibited significantly higher COPD assessment test score compared to those without cataract (13.7 ± 8.9 vs. 11.5 ± 7.2, p = 0.0240). Overall St George's Respiratory Questionnaire score and each component were significantly worse in COPD patients with cataract compared to those without cataract. COPD patients with cataract exhibited poor health-related quality of life and frequent exacerbations. The association between cataract and exacerbations of COPD deserves further attention.


Assuntos
Catarata/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Qualidade de Vida , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Comorbidade , Progressão da Doença , Feminino , Nível de Saúde , Humanos , Hipertensão/epidemiologia , Japão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Inquéritos e Questionários
11.
J Clin Microbiol ; 54(3): 699-704, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26739154

RESUMO

The nontuberculous mycobacteria (NTM) cause miscellaneous disorders in humans, especially in the lungs, which present with a variety of radiological features. To date, knowledge of the pathogenic role of the Mycobacterium avium-intracellulare complex (MAC) in the human lung and the definitive criteria for initiating multidrug therapy are still lacking. However, there is little doubt that clarithromycin is the most efficacious drug among the various treatment regimens for lung NTM. In this study, with the use of a bridged nucleic acid (BNA) probe a detection system based on a real-time PCR (BNA-PCR) for the identification of the point mutations at position 2058 or 2059 in domain V of the 23S rRNA gene responsible for clarithromycin resistance was developed and has been assessed using MAC isolates from clinical samples. Out of 199 respiratory specimens, the drug susceptibility test demonstrated 12 strains resistant to clarithromycin, while the BNA-PCR showed 8 strains carrying the point mutation at position 2058 or 2059 of the 23S rRNA gene. This system revealed that there were mycobacterial strains resistant to clarithromycin which do not carry previously identified resistance genes. This paper documents a novel system for detecting clarithromycin-resistant strains and demonstrates that although these mutations are tacitly assumed to account for >90% of the reported resistant mutants, there is a significant fraction of resistant mutants that do not harbor these mutations. Therefore, unknown mechanisms affecting clarithromycin resistance remain to be elucidated.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana , Complexo Mycobacterium avium/efeitos dos fármacos , Complexo Mycobacterium avium/genética , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Infecção por Mycobacterium avium-intracellulare/microbiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Complexo Mycobacterium avium/classificação , Reação em Cadeia da Polimerase , RNA Ribossômico 23S/genética , Sensibilidade e Especificidade , Escarro/microbiologia
12.
Biotechnol Lett ; 38(4): 637-42, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26687199

RESUMO

OBJECTIVES: To develop a genome editing method using the CRISPR/Cas9 system in Aspergillus oryzae, the industrial filamentous fungus used in Japanese traditional fermentation and for the production of enzymes and heterologous proteins. RESULTS: To develop the CRISPR/Cas9 system as a genome editing technique for A. oryzae, we constructed plasmids expressing the gene encoding Cas9 nuclease and single guide RNAs for the mutagenesis of target genes. We introduced these into an A. oryzae strain and obtained transformants containing mutations within each target gene that exhibited expected phenotypes. The mutational rates ranged from 10 to 20 %, and 1 bp deletions or insertions were the most commonly induced mutations. CONCLUSIONS: We developed a functional and versatile genome editing method using the CRISPR/Cas9 system in A. oryzae. This technique will contribute to the use of efficient targeted mutagenesis in many A. oryzae industrial strains.


Assuntos
Aspergillus oryzae/genética , Sistemas CRISPR-Cas , Edição de Genes/métodos , Genoma Fúngico , Mutagênese , Taxa de Mutação
13.
World J Microbiol Biotechnol ; 32(3): 47, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26873558

RESUMO

A natural antibacterial-substance-producing gram-positive bacterium was isolated from terasi shrimp paste, a popular fermented product in Indonesia. This strain, a spore-forming and strictly aerobic bacterium, was identified as Virgibacillus salexigens by 16S rRNA gene sequence analysis. The antibacterial substance purified from the precipitated product in the culture supernatant of the strain using ammonium sulfate showed a broad inhibition spectrum against gram-positive bacteria, including a typical foodborne bacterium, namely, Listeria monocytogenes. The antibacterial activity of the substance was inactivated by treatments with various proteolytic enzymes. It was stable after heating or pH treatment, and approximately 60% of the initial activity remained even after heating at 121 °C for 15 min. In addition, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis indicated that its monoisotopic mass weight was 5318.4 Da (M+H)(+). On the basis of the results obtained by the automated Edman degradation technique and MALDI-TOF MS analysis, the substance can be classified as a member of Class IId bacteriocins, but it could not be identified as any of the previously purified substances except for the putative bacteriocin predicted from the draft genome sequence data of gram-positive bacteria such as Virgibacillus and Bacillus strains.


Assuntos
Bacteriocinas/metabolismo , Bacteriocinas/farmacologia , Microbiologia de Alimentos , Bactérias Gram-Positivas/efeitos dos fármacos , Virgibacillus/isolamento & purificação , Virgibacillus/metabolismo , Aerobiose , Bacteriocinas/isolamento & purificação , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Concentração de Íons de Hidrogênio , Indonésia , Peso Molecular , Proteólise , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Esporos Bacterianos/citologia , Temperatura , Virgibacillus/classificação , Virgibacillus/genética
15.
Respirology ; 20(2): 286-95, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25392953

RESUMO

BACKGROUND AND OBJECTIVE: Osteoporosis is an important systemic comorbidity of chronic obstructive pulmonary disease (COPD). However, neither its mechanisms nor its risk factors have been fully elucidated. With regard to genetic factors, low-density lipoprotein receptor-related protein 5 (LRP5) A1330V is known to be associated with osteoporosis in the general population, but the influence of this polymorphism in COPD is unknown. The aim of this study was to investigate the potential risk factors of COPD-related bone loss and fracture. METHODS: Keio University and affiliated hospitals have enrolled an observational cohort to investigate the management of COPD comorbidities. To assess risk factors for osteopenia and osteoporosis, bone mineral density (BMD) of the hip and lumbar spine, presence of vertebral fracture, quantitative data on emphysema and airway wall on computed tomography, as well as LRP5 genotype were analysed in patients with or at risk for COPD (n = 270). RESULTS: The percentage of subjects with osteoporosis (T-score ≤ -2.5), osteopenia (T-score between -1 and -2.5) and a normal BMD (T-score ≥ -1) was 15.2%, 35.9% and 48.9%, respectively. T-score was significantly decreased in subjects with LRP5 TT genotype (n = 15) compared with that in those with CC/CT genotype (n = 255) (-1.83 vs. -0.98, P = 0.0167). On multivariate logistic regression analysis, female gender (odds ratio (OR) 10.4; P < 0.0001), severe emphysema (OR 2.3; P = 0.013) and LRP5 TT genotype (OR 3.7; P = 0.031) independently increased the risk of osteopenia/osteoporosis. CONCLUSIONS: This study confirmed the complex pathophysiology of COPD-related osteoporosis, including the influence of gender, clinical phenotype and genetic factors.


Assuntos
Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Osteoporose/epidemiologia , Osteoporose/genética , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Densidade Óssea , Comorbidade , Feminino , Genótipo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo Genético , Estudos Prospectivos , Enfisema Pulmonar/diagnóstico por imagem , Radiografia , Fatores de Risco , Fatores Sexuais
16.
Respir Res ; 15: 13, 2014 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-24502760

RESUMO

BACKGROUND: The chronic obstructive pulmonary disease (COPD) Assessment Test (CAT) is a concise health status measure for COPD. COPD patients have a variety of comorbidities, but little is known about their impact on quality of life. This study was designed to investigate comorbid factors that may contribute to high CAT scores. METHODS: An observational study at Keio University and affiliated hospitals enrolled 336 COPD patients and 67 non-COPD subjects. Health status was assessed by the CAT, the St. Georges Respiratory Questionnaire (SGRQ), and all components of the Medical Outcomes Study Short-Form 36-Item (SF-36) version 2, which is a generic measure of health. Comorbidities were identified based on patients' reports, physicians' records, and questionnaires, including the Frequency Scale for the Symptoms of Gastro-esophageal reflux disease (GERD) and the Hospital Anxiety and Depression Scale. Dual X-ray absorptiometry measurements of bone mineral density were performed. RESULTS: The CAT showed moderate-good correlations with the SGRQ and all components of the SF-36. The presence of GERD, depression, arrhythmia, and anxiety was significantly associated with a high CAT score in the COPD patients. CONCLUSIONS: Symptomatic COPD patients have a high prevalence of comorbidities. A high CAT score should alert the clinician to a higher likelihood of certain comorbidities such as GERD and depression, because these diseases may co-exist unrecognized. TRIAL REGISTRATION: Clinical trial registered with UMIN (UMIN000003470).


Assuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Índice de Gravidade de Doença , Absorciometria de Fóton/métodos , Absorciometria de Fóton/normas , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico por imagem , Ansiedade/epidemiologia , Estudos de Coortes , Comorbidade , Depressão/diagnóstico por imagem , Depressão/epidemiologia , Feminino , Refluxo Gastroesofágico/diagnóstico por imagem , Refluxo Gastroesofágico/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Biomarkers ; 19(5): 368-77, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24842387

RESUMO

Chronic obstructive pulmonary disease (COPD) develops only in smoking-sensitive smokers and manifests heterogeneous phenotypes, including emphysema and non-emphysema types. We aimed to identify biomarkers related to the smoking-sensitivity and phenotypes of COPD. Among 240 smokers suggestive of COPD, we studied on four groups defined by % forced expiratory volume in one second (FEV1) and computed tomography-based pulmonary emphysema. Plasma concentrations of 33 inflammatory markers were measured in four groups as well as Non-smokers using multiplex protein arrays. IL-5, IL-7 and IL-13 were identified to be associated with smoking sensitivity and IL-6 and IL-10 were candidate biomarkers for airway-lesion dominant COPD.


Assuntos
Biomarcadores/sangue , Citocinas/sangue , Doença Pulmonar Obstrutiva Crônica/sangue , Fumar/sangue , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Interleucina-10/sangue , Interleucina-13/sangue , Interleucina-5/sangue , Interleucina-6/sangue , Interleucina-7/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/sangue , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/fisiopatologia , Fumar/fisiopatologia , Tomografia Computadorizada por Raios X
18.
Respir Investig ; 62(1): 49-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37948969

RESUMO

Recent advances in imaging analysis have enabled evaluation of ventilation and perfusion in specific regions by chest computed tomography (CT) and magnetic resonance imaging (MRI), in addition to modalities including dynamic chest radiography, scintigraphy, positron emission tomography (PET), ultrasound, and electrical impedance tomography (EIT). In this review, an overview of current functional imaging techniques is provided for each modality. Advances in chest CT have allowed for the analysis of local volume changes and small airway disease in addition to emphysema, using the Jacobian determinant and parametric response mapping with inspiratory and expiratory images. Airway analysis can reveal characteristics of airway lesions in chronic obstructive pulmonary disease (COPD) and bronchial asthma, and the contribution of dysanapsis to obstructive diseases. Chest CT is also employed to measure pulmonary blood vessels, interstitial lung abnormalities, and mediastinal and chest wall components including skeletal muscle and bone. Dynamic CT can visualize lung deformation in respective portions. Pulmonary MRI has been developed for the estimation of lung ventilation and perfusion, mainly using hyperpolarized 129Xe. Oxygen-enhanced and proton-based MRI, without a polarizer, has potential clinical applications. Dynamic chest radiography is gaining traction in Japan for ventilation and perfusion analysis. Single photon emission CT can be used to assess ventilation-perfusion (V˙/Q˙) mismatch in pulmonary vascular diseases and COPD. PET/CT V˙/Q˙ imaging has also been demonstrated using "Galligas". Both ultrasound and EIT can detect pulmonary edema caused by acute respiratory distress syndrome. Familiarity with these functional imaging techniques will enable clinicians to utilize these systems in clinical practice.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética/métodos
19.
Cureus ; 16(1): e53019, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38410298

RESUMO

BACKGROUND: Attention to physical activity has grown in patients with chronic obstructive pulmonary disease (COPD), as it serves as a robust indicator for mortality associated with COPD. Non-exercise activity thermogenesis (NEAT) is the energy expenditure due to physical activities besides active sports-like exercises and resistance training in daily life, and decreased NEAT may be related to physical inactivity in patients with COPD. We examined whether NEAT assessed using a questionnaire reflects clinical parameters in patients with or at risk for COPD. METHODS: The study participants consisted of 36 male patients (COPD=28; stage1=6, stage2=14, stage3/4=8, and at-risk for COPD=8) older than 50 years of age. The participants underwent anthropometric measurements, lung function testing, a six-minute walk test, muscle strength testing, and questionnaires, e.g., the COPD assessment test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and Hospital Anxiety and Depression Scale. Image analysis with chest computed tomography (CT) included the number of trunk muscles, bronchial wall thickening, and emphysema (percentage of the lung field occupied by low attenuation area <-950 HU). We evaluated the relationship between these clinical parameters and NEAT questionnaire scores using Pearson correlation analysis and the Tukey-Kramer test. RESULTS: The NEAT score was correlated with the severity of airflow limitation and airway wall thickness measured by chest CT, symptoms evaluated by the mMRC dyspnea scale and CAT, and inspiratory muscle strength and pectoralis muscle area assessed by CT. CONCLUSION: Our study revealed the significance of NEAT as a valuable indicator in assessing the health status of patients with or at risk for COPD. The NEAT score was correlated with various clinical traits, suggesting that incorporating NEAT assessments using a questionnaire can contribute to a comprehensive understanding of the clinical condition in these patients. Further large-scale studies are warranted to validate and generalize these findings across diverse COPD populations.

20.
Clin Oral Investig ; 17(2): 483-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22552594

RESUMO

OBJECTIVE: The objective of this study was to clarify differences in oral health status between patients who needed haemodialysis (HD) owing to diabetic nephropathy (DN) and chronic glomerulonephritis (CGN). MATERIALS AND METHODS: Ninety-eight HD patients who were 50-70 years old were selected as the study subjects [DN group (29 subjects) and CGN group (69 subjects)] to compare with 106 control subjects (control group) not undergoing HD. All HD subjects underwent oral- and systemic-related examination just before HD therapy. RESULTS: The mean number of teeth present in the DN group was significantly less than in the CGN and control groups. The mean percentage of sites with bleeding on probing in the DN group was greater than in the CGN and control groups. The mean salivary flow rate in the DN and CGN groups was significantly lower compared with the control group. CONCLUSION: The patients undergoing HD for DN were found to have fewer teeth and worse periodontal health compared with those undergoing HD for CGN and with the control subjects not undergoing HD. Furthermore, the dental and periodontal health of the patients undergoing HD for CGN was comparable to that of the controls. CLINICAL RELEVANCE: For effective measures of prevention and improvement of oral health in HD patients, clinicians should be aware of the differences in the characteristics of the oral health between patients undergoing HD for DN and CGN.


Assuntos
Nefropatias Diabéticas/terapia , Glomerulonefrite/terapia , Saúde Bucal , Diálise Renal , Idoso , Análise Química do Sangue , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Doença Crônica , Estudos Transversais , Índice CPO , Feminino , Hemorragia Gengival/classificação , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/classificação , Índice Periodontal , Bolsa Periodontal/classificação , Saliva/metabolismo , Taxa Secretória/fisiologia , Fumar , Perda de Dente/classificação , Xerostomia/classificação
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