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1.
Nature ; 600(7888): 319-323, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34819663

RESUMO

Lung cancer is one of the most aggressive tumour types. Targeted therapies stratified by oncogenic drivers have substantially improved therapeutic outcomes in patients with non-small-cell lung cancer (NSCLC)1. However, such oncogenic drivers are not found in 25-40% of cases of lung adenocarcinoma, the most common histological subtype of NSCLC2. Here we identify a novel fusion transcript of CLIP1 and LTK using whole-transcriptome sequencing in a multi-institutional genome screening platform (LC-SCRUM-Asia, UMIN000036871). The CLIP1-LTK fusion was present in 0.4% of NSCLCs and was mutually exclusive with other known oncogenic drivers. We show that kinase activity of the CLIP1-LTK fusion protein is constitutively activated and has transformation potential. Treatment of Ba/F3 cells expressing CLIP1-LTK with lorlatinib, an ALK inhibitor, inhibited CLIP1-LTK kinase activity, suppressed proliferation and induced apoptosis. One patient with NSCLC harbouring the CLIP1-LTK fusion showed a good clinical response to lorlatinib treatment. To our knowledge, this is the first description of LTK alterations with oncogenic activity in cancers. These results identify the CLIP1-LTK fusion as a target in NSCLC that could be treated with lorlatinib.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Transformação Celular Neoplásica/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Associadas aos Microtúbulos/genética , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Receptores Proteína Tirosina Quinases/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Transformação Celular Neoplásica/efeitos dos fármacos , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 15/genética , Humanos , Lactamas/farmacologia , Lactamas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Camundongos Nus , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
2.
J Infect Chemother ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39089446

RESUMO

INTRODUCTION: Antimicrobial treatment disrupts human microbiota. The effects of lascufloxacin (LSFX), a new fluoroquinolone, on human microbiota remains unknown. Therefore, in this study, we aimed to evaluate the effects of LSFX administration on the gut and salivary microbiota of healthy participants and those with pneumonia. METHODS: LSFX (75 mg, once a day, orally) was administered to healthy adults (healthy group) and adult patients with pneumonia (pneumonia group), and fecal and saliva samples were collected at five time points (Days 0, 3, 7, 14, and 28). Using the collected samples, α- and ß-diversity indices, as well as bacterial composition of the gut microbiota and salivary microbiota were analyzed using next-generation sequencing. RESULTS: In the healthy group, α-diversity indices of the gut and salivary microbiota were reduced and the lowest values on Day 3. For the gut microbiota, the Chao1 index (richness) recovered on Day 28, whereas the Shannon index (evenness) did not. In the salivary microbiota, the Chao1 and Shannon indices did not recover within the 28 day period. The ß-diversity indices changed after LSFX administration and subsequently recovered on Day 28. After LSFX administration, the abundance of the Lachnospiraceae family decreased in the gut microbiota, and the abundance of Granulicatella, Streptococcus, Prevotella, Absconditabacteriales(SR1), and Saccharimonadales decreased in the salivary microbiota. In the pneumonia group, the α-diversity indices were lowest on Day 14 after LSFX administration. CONCLUSIONS: We elucidated that LSFX administration differentially affected the gut and salivary microbiota; however, the richness and beta diversity recovered within 28 days.

3.
Artigo em Inglês | MEDLINE | ID: mdl-37545323

RESUMO

Heart failure and pneumonia are highly prevalent in elderly patients. We conducted a study to evaluate the differences in the patterns of symptoms, laboratory findings, and computed tomography (CT) results in elderly patients with acute cardiogenic pulmonary edema (ACPE) and community-acquired pneumonia (CAP). From January 1, 2015 to December 31, 2017, we studied 140 patients aged >75 years who were diagnosed with ACPE and CAP. Symptoms, laboratory findings, mean ostial pulmonary vein (PV) diameter and patterns on CT images were assessed. The primary measures of diagnostic accuracy were assessed using the positive likelihood ratio (LR+). The cutoff value of ostial PVs for differentiating patients with ACPE from CAP was evaluated using the receiver operating characteristic (ROC) analysis. Ninety-three patients with ACPE, 36 with CAP, and 11 with complicated ACPE/CAP were included. In patients with ACPE, edema (LR+ 5.4) was a moderate factor for rule-in, and a high brain natriuretic peptide level (LR+ 4.2) was weak. In patients with CAP, cough (LR+ 5.7) and leukocytosis (LR+ 5.2) were moderate factors for rule-in, while fever (LR+ 3.8) and a high C-reactive protein level (LR+ 4.8) were weak factors. The mean diameter of ostial PVs in patients with ACPE was significantly larger than that of patients with CAP (15.8±â€Š1.8 mm vs 9.6±1.5 mm, p< 0.01). ROC analysis revealed that an ostial PV diameter cutoff of 12.5 mm was strong evidence for distinguishing ACPE from CAP with an area under the ROC curve of 0.99 and LR+ 36.0. In conclusion, as ACPE and CAP have similar symptoms and laboratory findings, dilated ostial PVs were useful in characterizing CT images to distinguish ACPE from CAP.

4.
Respir Res ; 23(1): 365, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539765

RESUMO

RATIONALE: Bronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control. OBJECTIVE: We determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them. METHODS: We conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed. RESULTS: In total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO. CONCLUSIONS: Bronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.


Assuntos
Asma , Bronquiectasia , Humanos , Óxido Nítrico/análise , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Eosinófilos , Bronquiectasia/diagnóstico , Bronquiectasia/tratamento farmacológico , Bronquiectasia/epidemiologia , Corticosteroides/uso terapêutico , Expiração
5.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575973

RESUMO

Radiation damages many cellular components and disrupts cellular functions, and was previously reported to impair locomotion in the model organism Caenorhabditis elegans. However, the response to even higher doses is not clear. First, to investigate the effects of high-dose radiation on the locomotion of C. elegans, we investigated the dose range that reduces whole-body locomotion or leads to death. Irradiation was performed in the range of 0-6 kGy. In the crawling analysis, motility decreased after irradiation in a dose-dependent manner. Exposure to 6 kGy of radiation affected crawling on agar immediately and caused the complete loss of motility. Both γ-rays and carbon-ion beams significantly reduced crawling motility at 3 kGy. Next, swimming in buffer was measured as a motility index to assess the response over time after irradiation and motility similarly decreased. However, swimming partially recovered 6 h after irradiation with 3 kGy of γ-rays. To examine the possibility of a recovery mechanism, in situ GFP reporter assay of the autophagy-related gene lgg-1 was performed. The fluorescence intensity was stronger in the anterior half of the body 7 h after irradiation with 3 kGy of γ-rays. GFP::LGG-1 induction was observed in the pharynx, neurons along the body, and the intestine. Furthermore, worms were exposed to region-specific radiation with carbon-ion microbeams and the trajectory of crawling was measured by image processing. Motility was lower after anterior-half body irradiation than after posterior-half body irradiation. This further supported that the anterior half of the body is important in the locomotory response to radiation.


Assuntos
Autofagia/efeitos da radiação , Locomoção/efeitos da radiação , Doses de Radiação , Animais , Autofagia/fisiologia , Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/efeitos da radiação , Relação Dose-Resposta à Radiação , Raios gama/efeitos adversos , Humanos , Locomoção/fisiologia , Irradiação Corporal Total/efeitos adversos
6.
Mod Rheumatol ; 31(3): 629-635, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32820678

RESUMO

OBJECTIVES: Pneumocystis pneumonia (PCP) is a life-threatening opportunistic infection. Sulfamethoxazole-trimethoprim (SMX/TMP) is the first-line drug for PCP prophylaxis. However, adverse events (AEs) force clinicians to alter or reduce the drug dosage. METHODS: We retrospectively reviewed all patients with rheumatic diseases who received SMX/TMP for prophylaxis and glucocorticoid therapy between April 2004 and March 2018. The rates of AEs, SMX/TMP discontinuation, and incidence of PCP were analyzed. Patients were divided into the conventional group and the dose-reduction group. RESULTS: One hundred forty-five patients and 75 patients were included in the conventional group and the dose-reduction group, respectively. Compared to the dose-reduction group, the conventional group had a significantly high frequency of AEs (10.7% vs. 24.1%; p = .017); however, the rate of discontinuing SMX/TMP was not significantly different (8.0% vs. 14.5%; p = .165). Thirteen conventional group patients required a reduced SMX/TMP dose because of AEs; no patient developed PCP. The conventional SMX/TMP dose and renal dysfunction were associated with AEs in multivariate analysis. CONCLUSION: Patients who received a reduced SMX/TMP dose did not have PCP and had a lower frequency of AEs. A reduction in SMX/TMP for PCP prophylaxis is effective and safe in patients with rheumatic disease.


Assuntos
Antibacterianos/uso terapêutico , Quimioprevenção/métodos , Pneumonia por Pneumocystis/prevenção & controle , Doenças Reumáticas/complicações , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Quimioprevenção/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/tratamento farmacológico , Estudos Retrospectivos , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
7.
J Gastroenterol Hepatol ; 35(2): 211-217, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31396997

RESUMO

BACKGROUND AND AIM: The study aims to clarify the endoscopic features and clinicopathological differences in superficial Barret's esophageal adenocarcinoma (s-BEA) derived from short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE). METHODS: We reviewed data of 130 patients (141 lesions) with pathologically confirmed s-BEA (SSBE: 95 patients and 95 lesions; LSBE: 35 patients and 46 lesions). We analyzed endoscopic and clinicopathological features of s-BEA in patients with SSBE and LSBE. RESULTS: The distribution of lesions according to macroscopic findings were as follows (s-BEA in SSBE vs LSBE): flat type (0-IIb), 3.2% (3/95) vs 32.6% (15/46) (P < 0.001); accompanied type 0-IIb, 2.1% (2/95) vs 21.7% (10/46) (P < 0.001); and complex type (0-I + IIb, 0-IIa + IIc, etc.), 30.5% (29/95) vs 50.0% (23/46) (P = 0.025). Complex-type s-BEAs had high incidences of T1b invasions and poorly differentiated components (simple type: 22.5% [20/89] and 18.0% [16/89]; complex type: 59.6% [31/52] and 44.2% [23/52], P < 0.001 and P = 0.002, respectively). In SSBE, 72.6% (69/95) of lesions were located at the right anterior wall (P = 0.01). All flat-type or depressed-type lesions derived from SSBE were identified as reddish areas, whereas only 65.2% (15/23) from LSBE were identified as reddish areas (P < 0.001). CONCLUSIONS: In LSBE, flat-type, accompanied-type 0-IIb, and complex-type lesions were significantly more prevalent. Furthermore, complex-type s-BEAs tended to have T1b invasions and poorly differentiated components. S-BEAs in LSBE should be more carefully evaluated on endoscopic appearance including flat-type and complex-type lesions than in SSBE.


Assuntos
Adenocarcinoma/patologia , Esôfago de Barrett/patologia , Endoscopia , Neoplasias Esofágicas/patologia , Esôfago/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Int J Clin Pharmacol Ther ; 57(7): 353-361, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31094316

RESUMO

OBJECTIVE: In elderly patients, age-related, disease-related, and drug-related factors are associated with chronic kidney disease (CKD). Little is known about which factors are the best predictors for CKD in elderly patients. MATERIALS AND METHODS: The study was based on 784 patients aged 75 years or older for whom the clinical and serum creatinine on admission to our hospital were available. Impaired renal function, including CKD and transient renal insufficiency, was defined as a non-indexed glomerular filtration rate (GFR) below 60 mL/min. A logistic regression model was developed for predictors of CKD and was internally validated using bootstrapping. RESULTS: Approximately 61% of the patients, who had CKD (46%) and transient renal insufficiency (15%), had a non-indexed GFR < 60 mL/min. Synergistic use of 3 drugs potentially impairing renal function, diuretics, ACE-I/ARB, and NSAIDs (odds ratio (OR), 4.66; 95% confidence interval (CI), 1.48 - 17.7, p = 0.012) was a significantly associated factor for CKD in a multivariate logistic regression analysis. Age (OR 1.56, 95% CI 1.04 - 2.33, p = 0.03), female gender (OR 1.58, 95% CI 1.04 - 2.39, p = 0.03), any prescription ACE-I/ARB either alone or in combinations with diuretics or NSAIDs (OR 2.74, 95% CI 1.83 - 4.13, p = 0.0001), and proteinuria (OR 1.98, 95% CI 1.27 - 3.10, p = 0.003), were included as the best model for CKD. The area under the curve (AUC) of the best model and the bootstrapping validation were 0.68 and 0.71, respectively. CONCLUSION: Given the widespread use of ACE-I/ARB for elderly patients, our findings suggest that caution is needed when they are prescribed because of the possibility of the patient developing CKD.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Diuréticos/efeitos adversos , Prescrição Inadequada/estatística & dados numéricos , Insuficiência Renal Crônica/induzido quimicamente , Idoso , Creatinina/sangue , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Pacientes Internados , Masculino
9.
Allergol Int ; 68(4): 456-461, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31153755

RESUMO

BACKGROUND: We explored whether the use of deep learning to model combinations of symptom-physical signs and objective tests, such as lung function tests and the bronchial challenge test, would improve model performance in predicting the initial diagnosis of adult asthma when compared to the conventional machine learning diagnostic method. METHODS: The data were obtained from the clinical records on prospective study of 566 adult out-patients who visited Kindai University Hospital for the first time with complaints of non-specific respiratory symptoms. Asthma was comprehensively diagnosed by specialists based on symptom-physical signs and objective tests. Model performance metrics were compared to logistic analysis, support vector machine (SVM) learning, and the deep neural network (DNN) model. RESULTS: For the diagnosis of adult asthma based on symptom-physical signs alone, the accuracy of the DNN model was 0.68, whereas that for the SVM was 0.60 and for the logistic analysis was 0.65. When adult asthma was diagnosed based on symptom-physical signs, biochemical findings, lung function tests, and the bronchial challenge test, the accuracy of the DNN model increased to 0.98 and was significantly higher than the 0.82 accuracy of the SVM and the 0.94 accuracy of the logistic analysis. CONCLUSIONS: DNN is able to better facilitate diagnosing adult asthma, compared with classical machine learnings, such as logistic analysis and SVM. The deep learning models based on symptom-physical signs and objective tests appear to improve the performance for diagnosing adult asthma.


Assuntos
Asma/diagnóstico , Aprendizado Profundo , Modelos Teóricos , Algoritmos , Inteligência Artificial , Feminino , Humanos , Modelos Logísticos , Masculino , Redes Neurais de Computação , Curva ROC , Máquina de Vetores de Suporte
10.
Digestion ; 97(4): 316-323, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29539629

RESUMO

BACKGROUND: In recent years, effective outcomes of endoscopic submucosal dissection (ESD) for esophagogastric junction cancer including short-segment Barrett's esophagus (SSBE) cancer have been reported. However, the efficacy of ESD for long-segment Barrett's esophagus (LSBE) cancer is unknown. AIM: To clarify the treatment outcomes of ESD for LSBE cancer versus SSBE cancer. METHODS: A total of 86 patients with 91 superficial Barrett's esophageal adenocarcinomas who underwent ESD were enrolled; of these, 68 had underlying SSBE and 18 had LSBE. Procedure outcomes and prognosis were compared. RESULTS: There was no significant difference in age and tumor diameter among patients. The only complication observed was stricture, but it was not significant (2 vs. 9%). No significant difference was observed in the negative horizontal margin rates (94.1 vs. 95.7%), R0 resection rates (83.8 vs. 82.6%), curative resection rates (72.1 vs. 73.9%), and noncurative factors. Both LSBE and SSBE cancer showed favorable 3-year overall survival rates (95.0 vs. 94.4%) in the median observation period of 28.5 months. CONCLUSIONS: ESD for LSBE cancer achieved procedure outcomes and short-term prognosis comparable to SSBE. ESD has the potential to be an effective therapeutic option for esophageal neoplasms in patients with LSBE.


Assuntos
Adenocarcinoma/cirurgia , Esôfago de Barrett/patologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Neoplasias Esofágicas/cirurgia , Esofagoscopia/efeitos adversos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Esôfago de Barrett/mortalidade , Esôfago de Barrett/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Estenose Esofágica/epidemiologia , Estenose Esofágica/etiologia , Esofagoscopia/métodos , Esôfago/fisiologia , Esôfago/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
Digestion ; 97(2): 170-176, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29310111

RESUMO

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a well-established minimally invasive treatment for early gastric cancer. To heal ESD-induced ulcers, we commonly prescribe proton pump inhibitors (PPIs). Vonoprazan is our new choice, which is reported to have a stronger and longer acid inhibitory effect than existing PPIs. Here, we aimed to evaluate the efficacy of vonoprazan for healing ESD-induced ulcers compared with rabeprazole. METHODS: We reviewed 190 patients who underwent ESD before and after we switched the acid secretion inhibitor from rabeprazole to vonoprazan. We evaluated scarring and reduction rates at 4 weeks after ESD. RESULTS: Scarring rates were not different between vonoprazan and rabeprazole (31.7 vs. 18.9%; p = 0.07). However, for ulcers ≤35 mm, vonoprazan was superior to rabeprazole (42.2 vs. 19.2%; p < 0.05). Reduction rates were superior for vonoprazan compared with rabeprazole (93.0 vs. 90.4%; p < 0.05). In multivariate analysis, vonoprazan was superior to rabeprazole for ulcer scarring (OR 2.21; p < 0.05), and ulcer location in the lower-third of the stomach had higher risk of incomplete scarring (OR 0.37; p < 0.05). CONCLUSION: Vonoprazan was superior to rabeprazole for healing ESD-induced ulcers.


Assuntos
Ressecção Endoscópica de Mucosa/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Pirróis/uso terapêutico , Rabeprazol/uso terapêutico , Neoplasias Gástricas/cirurgia , Úlcera Gástrica/tratamento farmacológico , Sulfonamidas/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Medicamentos/métodos , Feminino , Gastroscopia/efeitos adversos , Gastroscopia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Estômago/diagnóstico por imagem , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/patologia , Úlcera Gástrica/diagnóstico por imagem , Úlcera Gástrica/etiologia
13.
Allergol Int ; 65(1): 56-61, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26666494

RESUMO

BACKGROUND: An important aspect of sand dust emissions in association with respiratory disorders is the quantity of particulate matter. This is usually expressed as particulate matter less than 10 µm (PM10) and 2.5 µm (PM2.5). However, the composition of PM10 and PM2.5 varies. Light detection and ranging is used to monitor sand dust particles originating in East Asian deserts and distinguish them from air pollution aerosols. The objective of this study was to investigate the association between the daily levels of sand dust particles and pulmonary function in schoolchildren in western Japan. METHODS: In this panel study, the peak expiratory flow (PEF) of 399 schoolchildren was measured daily from April to May 2012. A linear mixed model was used to estimate the association of PEF with the daily levels of sand dust particles, suspended particulate matter (SPM), and PM2.5. RESULTS: There was no association between the daily level of sand dust particles and air pollution aerosols, while both sand dust particles and air pollution aerosols had a significant association with SPM and PM2.5. An increment of 0.018 km(-1) in sand dust particles was significantly associated with a decrease in PEF (-3.62 L/min; 95% confidence interval, -4.66 to -2.59). An increase of 14.0 µg/m(3) in SPM and 10.7 µg/m(3) in PM2.5 led to a significant decrease of -2.16 L/min (-2.88 to -1.43) and -2.58 L/min (-3.59 to -1.57), respectively, in PEF. CONCLUSIONS: These results suggest that exposure to sand dust emission may relate to pulmonary dysfunction in children in East Asia.


Assuntos
Poluentes Atmosféricos , Poeira , Hipersensibilidade/etiologia , Hipersensibilidade/fisiopatologia , Material Particulado , Pico do Fluxo Expiratório , Criança , Pré-Escolar , Feminino , Humanos , Hipersensibilidade/epidemiologia , Japão/epidemiologia , Masculino , Vigilância em Saúde Pública , Testes de Função Respiratória , Fatores de Risco
14.
Allergol Int ; 65(2): 147-152, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26666479

RESUMO

BACKGROUND: Asian dust (AD) has become a major health concern. The concentration of AD is typically expressed in particulate matter less than 10 µm (PM10) and 2.5 µm (PM2.5). However, PM10 and PM2.5 consist of various substances besides AD. Light detection and ranging (LIDAR) systems can selectively measure the quantity of AD particles to distinguish non-spherical airborne particles from spherical airborne particles. The objective of this study was to investigate the relationship between pulmonary function in adult asthma patients and AD using LIDAR data. METHODS: Subjects were 231 adult asthma patients who had their morning peak expiratory flow (PEF) measured from March to May 2012. A linear mixed model was used to estimate the association of PEF with sand dust particles detected by LIDAR. RESULTS: Increases in the interquartile range of AD particles (0.018 km(-1)) led to changes in PEF of -0.42 L/min (95% confidence interval [CI], -0.85 to 0.01). An increase of 11.8 µg/m(3) in suspended particulate matter and 6.9 µg/m(3) in PM2.5 led to decreases of -0.17 L/min (-0.53 to 0.21) and 0.03 L/min (-0.35 to 0.42), respectively. A heavy AD day was defined as a day with a level of AD particles >0.032 km(-1), which was the average plus one standard deviation during the study period, and six heavy AD days were identified. Change in PEF after a heavy AD day was -0.97 L/min (-1.90 to -0.04). CONCLUSIONS: Heavy exposure to AD particles was significantly associated with decreased pulmonary function in adult asthma patients.


Assuntos
Asma/etiologia , Asma/fisiopatologia , Poeira , Testes de Função Respiratória , Idoso , Asma/epidemiologia , Comorbidade , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Material Particulado/efeitos adversos , Pico do Fluxo Expiratório , Fatores de Risco
15.
Pulm Pharmacol Ther ; 32: 45-52, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25956071

RESUMO

AIMS: Vitamin E is an antioxidant that occurs in 8 different forms (α, ß, γ, and δ tocopherol and tocotrienol). Clinical trials of tocopherol supplementation to assess the impact of antioxidant activity in asthma have yielded equivocal results. Tocotrienol exhibits greater antioxidant activity than tocopherol in several biological phenomena in vivo and in vitro. We tested the effect of tocotrienol on human airway smooth muscle (ASM) cell growth and migration, both of which mediate airway remodeling in asthma. MAIN METHODS: We measured platelet-derived growth factor-BB (PDGF-BB)-induced ASM cell proliferation and migration by colorimetric and Transwell migration assays in the presence and absence of γ-tocotrienol (an isoform of tocotrienol). KEY FINDINGS: PDGF-BB-induced ASM cell proliferation and migration were inhibited by γ-tocotrienol. This effect was associated with inhibition of RhoA activation, but it had no effect on p42/p44 mitogen-activated protein kinase (MAPK) or Akt1 activation. We confirmed that pharmacological inhibition of Rho kinase activity was sufficient to inhibit PDGF-BB-induced ASM cell proliferation and migration. SIGNIFICANCE: γ-Tocotrienol could impart therapeutic benefits for airway remodeling in asthma by inhibiting human ASM cell proliferation and migration.


Assuntos
Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Cromanos/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Vitamina E/análogos & derivados , Remodelação das Vias Aéreas/efeitos dos fármacos , Becaplermina , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Colorimetria , Humanos , Miócitos de Músculo Liso/metabolismo , Proteínas Proto-Oncogênicas c-sis/administração & dosagem , Vitamina E/farmacologia
17.
Nihon Shokakibyo Gakkai Zasshi ; 112(1): 86-93, 2015 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-25744924

RESUMO

A 52-year-old male visited a local clinic with a subjective complaint of pain in the left side of his abdomen. Abdominal CT revealed the presence of a pancreatic body tumor. On EUS, the tumor presented hypoechoic signals with an obscure boundary, which continued from the pancreatic parenchyma to the inside of the main pancreatic duct. Abdominal contrast CT revealed a hypervascular tumor with densely stained pancreatic parenchyma. ERP findings revealed that main pancreatic duct invasion was suspected based on partial radiolucency in the duct. Distal pancreatectomy was performed, and a definitive diagnosis of pancreatic neuroendocrine tumor (WHO class G1) was made histopathologically.


Assuntos
Ductos Pancreáticos/patologia , Neoplasias Pancreáticas/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Invasividade Neoplásica , Pancreatectomia , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X
18.
J Asthma ; 51(6): 595-602, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24628524

RESUMO

OBJECTIVE: Asian dust storms (ADS) contain various airborne particles that may augment airway inflammation by increasing the level of interleukin-8. The objective of the study was to investigate the association of exposure to an ADS with worsening of symptoms of adult asthma and the effect of ADS particles on interleukin-8 transcriptional activity. METHODS: The subjects were 112 patients with mild to moderate asthma who recorded scores for their daily upper and lower respiratory tract symptoms and measured morning peak expiratory flow (PEF) from March to May 2011. Interleukin-8 transcriptional activity was assessed in THP-G8 cells that were exposed to airborne particles collected during days of ADS exposure. RESULTS: Of the 112 patients, 31 had comorbid allergic rhinitis (AR) and/or chronic sinusitis (CS), and had worsened scores for upper respiratory tract symptoms on ADS days compared to non-ADS days. Scores for lower respiratory tract symptoms during ADS days were higher than non-ADS days in all patients. Three patients also had unscheduled hospital visits for exacerbation of asthma on ADS days. However, there was no significant difference in daily morning PEF between ADS and non-ADS days. Airborne particles collected on ADS days induced interleukin-8 transcriptional activity in THP-G8 cells compared to the original soil of the ADS. CONCLUSION: Exposure to an ADS aggravates upper and lower tract respiratory symptoms in patients with adult asthma. ADS airborne particles may increase airway inflammation through enhancement of interleukin-8 transcriptional activity.


Assuntos
Asma/imunologia , Poeira/imunologia , Interleucina-8/biossíntese , Vento , Idoso , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/imunologia , Asma/epidemiologia , Poeira/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Japão/epidemiologia , Luciferases/genética , Masculino , Pessoa de Meia-Idade , Material Particulado/análise , Material Particulado/imunologia , Pico do Fluxo Expiratório , Rinite Alérgica , Rinite Alérgica Perene/epidemiologia , Rinite Alérgica Perene/imunologia , Sinusite/epidemiologia , Sinusite/imunologia
19.
J Manipulative Physiol Ther ; 37(9): 719-25, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25455836

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effect of different recumbent positions on pulmonary function, chest wall motion, and feelings of discomfort in young nonobese healthy volunteers. METHODS: Twenty healthy volunteers (age, 28.0±1.4 years; height, 167.5±10.1 cm; weight, 62.3±10.2 kg) were studied in the sitting position and in the following 6 recumbent positions: supine, left retroversion at a 45° tilt, left anteversion at a 45° tilt, right retroversion at a 45° tilt, right anteversion at a 45° tilt, and prone. After 5 minutes of a selected position, pulmonary functions, including vital capacity (VC), forced expiratory volume in 1 second, maximal inspiratory and expiratory mouth pressures (MIP and MEP, respectively), and breathing pattern components at the chest wall were assessed. Discomfort was assessed using a modified Borg scale. RESULTS: When participants changed position from sitting to each of the 6 recumbent positions, forced expiratory volume in 1 second values decreased significantly (P < .05). None of the participants showed changes in the MIP or MEP in any of the 6 recumbent positions. Rib cage motion was restricted in all recumbent positions except supine, left anteversion at a 45° tilt, and prone. In all 6 recumbent positions, discomfort was experienced during the pulmonary tests. However, in the left retroversion at a 45° tilt position, no discomfort was experienced during the MIP and MEP assessments. CONCLUSION: In young, nonobese, healthy volunteers, recumbent positions caused diminished pulmonary functions and induced feelings of discomfort.


Assuntos
Voluntários Saudáveis , Movimento (Física) , Postura/fisiologia , Parede Torácica/fisiologia , Capacidade Vital/fisiologia , Adulto , Antropometria , Feminino , Humanos , Masculino , Decúbito Ventral/fisiologia , Valores de Referência , Testes de Função Respiratória , Estudos de Amostragem , Estatísticas não Paramétricas , Decúbito Dorsal/fisiologia , Adulto Jovem
20.
Respirol Case Rep ; 12(6): e01399, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38868561

RESUMO

We report a rare case of pulmonary Mycobacterium shinjukuense infection with cavitary lesion. Chemotherapy with rifampicin, ethambutol, and clarithromycin was effective for the lesion.

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