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1.
Artigo em Inglês | MEDLINE | ID: mdl-33805162

RESUMO

Long diagnostic delays (LDDs) may decrease the effectiveness of patient isolation in reducing subsequent transmission of coronavirus disease 2019 (COVID-19). This study aims to investigate the correlation between the proportion of LDD of COVID-19 patients with unknown transmission routes and the subsequent doubling time. LDD was defined as the duration between COVID-19 symptom onset and confirmation ≥6 days. We investigated the geographic correlation between the LDD proportion among 369 confirmed COVID-19 patients with symptom onset between the 9th and 11th week and the subsequent doubling time for 717 patients in the 12th-13th week among the six prefectures. The doubling time on March 29 (the end of the 13th week) ranged from 4.67 days in Chiba to 22.2 days in Aichi. Using a Pearson's product-moment correlation (p-value = 0.00182) and multiple regression analyses that were adjusted for sex and age (correlation coefficient -0.729, 95% confidence interval: -0.923--0.535, p-value = 0.0179), the proportion of LDD for unknown exposure patients was correlated inversely with the base 10 logarithm of the subsequent doubling time. The LDD for unknown exposure patients was correlated significantly and inversely with the subsequent doubling time.


Assuntos
Diagnóstico Tardio , Humanos , Japão/epidemiologia , Isolamento de Pacientes
2.
Biosens Bioelectron ; 179: 113077, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33607416

RESUMO

Hydrogen peroxide (H2O2) is one of the main second messengers involved in signaling pathways controlling cell metabolism. During tumorigenesis H2O2 is generated on the extracellular space by membrane-associated NADPH oxidases and superoxide dismutase to stimulate cell proliferation and preservation of the transformed state. Accordingly, a characteristic feature of malignant cells is overproduction of H2O2 in the extracellular milieu and the subsequent absorption in the cytosol. Since the most significant gradients of endogenous extracellular H2O2 can be observed only in a very shallow region of the fluid in contact with the plasma membrane, we show here the use of a newly designed nanosensor anchored to the outer cell surface and capable of quantifying H2O2 at nanometer distance from the membrane proteins responsible for its production. This biosensor is built upon gold nanoparticles functionalized with a H2O2-sensitive boronate compound that is probed using surface enhanced Raman spectroscopy (SERS). The highly localized information obtained on the cell surface by SERS analysis is combined with analytical methods of redox biology to estimate the associated levels of intracellular H2O2 responsible for cell signaling. The results obtained from A549 lung cancer cell line show localized spots on the cell surface at concentration up to 12 µM, associated to intracellular concentration up to 5.1 nM.

3.
J Gastroenterol ; 56(3): 261-273, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33427937

RESUMO

BACKGROUND: Although type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates. METHODS: The study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls. Clinical data at the time of and 5 years before HCC diagnosis were collected. RESULTS: The mean patient age at HCC diagnosis was approximately 73 years, and 80% of the patients were male. The proportion of patients with insulin use increased, whereas the body mass index (BMI), proportion of patients with fatty liver, fasting glucose levels, and hemoglobin A1c (HbA1c) levels decreased significantly in 5 years. In the cohort study, 18 patients developed HCC during the mean follow-up period of 4.7 years with an annual incidence of 0.11%. Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of HCC development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher BMI and gamma-glutamyl transpeptidase levels. Receiver-operating characteristic analyses showed that a FIB-4 cut-off value of 3.61 could help identify high-risk patients, with a corresponding annual HCC incidence rate of 1.1%. CONCLUSION: A simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology.

4.
PLoS One ; 15(12): e0243374, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33284809

RESUMO

BACKGROUND: We previously developed the Tobacco Craving Index (TCI) to assess craving of smokers. In the present study, we validated the relationship between the TCI grade over the 5 sessions of Japanese smoking cessation therapy (SCT) and success of quitting smoking among 889 Japanese patients. METHODS: The Japanese SCT consists of 5 sessions of SCT (first session and sessions 2, 4, 8 and 12 weeks later). In the TCI questionnaire, patients are asked to rate their strength of craving and frequency of craving, each on a four-point Likert scale. Patients are classified into one of four grades based on their responses (0, I, II, III, with III indicating severe craving). The TCI questionnaire was administered to each participant at each session of the SCT. This study included participants of Japanese SCT who answered the TCI at the first session of the SCT at five Japanese smoking cessation clinics. Patients who dropped out of the SCT from the second to the fifth sessions were considered to have failed smoking cessation. To elucidate how much the TCI grade predicts smoking status at the last session, we performed multivariate logistic regression analysis with adjustment for confounding factors. RESULTS: Participants who had higher TCI grade(III) in the 2nd through 5th sessions showed significantly lower probability for success of quitting smoking than those who had lower TCI grades(0 or I) (adjusted odds ratio: 2nd session: 0.30, 3rd session: 0.15, 4th session: 0.06, 5th session: 0.02). CONCLUSIONS: We validated the usefulness of the TCI grade for assessing probability of quitting smoking by using a large number of smoking cessation settings.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33233409

RESUMO

Long diagnostic delays (LDDs) in patients with coronavirus disease 2019 (COVID-19) might decrease the effectiveness of patient isolation in reducing subsequent transmission. We assumed that direction of government considerably increased probability of LDD among COVID-19 cases with unknown exposure in Japan. This study aimed to investigate association of route of case detection and proportion of LDD of COVID-19 in Japan. We included confirmed COVID-19 patients with symptom onset between the ninth and eleventh week in 2020, in 6 prefectures of Japan. LDD was defined as the duration between COVID-19 symptom onset and confirmation ≥6 days. We used multivariable logistic regression analyses to elucidate factors associated with LDD. The mean diagnostic delay for 364 cases was 6.3 days. Proportion of LDD was 38% for cases with known exposure, and 65% for cases with unknown exposure. The probability of LDD in cases with unknown exposure was significantly higher than that for known exposure cases (adjusted odds ratio: 2.38, 95% confidence interval: 1.354-4.21). Early PCR test after symptom onset, strengthening of PCR test capacity, and investigations to study impact of high proportion of LDD in cases without known exposure might be necessary.

6.
J Epidemiol ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32963210

RESUMO

BACKGROUND: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants. METHODS: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history, and collected peripheral blood samples. RESULTS: The baseline survey included 92,610 adults (mean age: 55.2 [9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women. CONCLUSIONS: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.

7.
Jpn J Nurs Sci ; : e12369, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32856408

RESUMO

AIM: This study aimed to develop a detection scale for intimate partner violence (DS-IPV), excluding physical and sexual violence, and to validate the scale. METHODS: A cross-sectional survey was undertaken using an anonymous 26-item self-administered questionnaire with volunteer women aged 18-59 residing in one prefecture in Japan. A total of 1,937 responses were obtained, and 1,915 were valid. The responses of the 1,277 women who had a partner at the time were included in the analysis. Statistical analysis examined exploratory/confirmatory factor analysis, internal consistency, and construct validity. RESULTS: A four-factor scale with 22 items was extracted for the DS-IPV. In the confirmatory factor analysis, the indices of fitness supported these results. Prior to the factor analysis, the Kiser-Mayer-Olkin measurement (.936) and Bartlett's sphericity test (p < .001) showed that all samples met the statistical criteria. Cronbach's alpha coefficient was .92 for total score and varied between .70 and .90 for each of the four factors, and internal consistency was confirmed. The following four factors emerged from an oblique factor analysis, with a cumulative variance of 58.1%: "arousing anxiety"; "controlling behavior"; "coercion and threat"; and "daily emotions". These four factors had a moderate correlation (.23-.48, p < .01) with each other, which indicated construct validity. Confirmatory factor analysis showed the indices of fitness supported these results. CONCLUSIONS: The DS-IPV scale, a concise scale to detect and screen for potential intimate partner violence, was developed. The DS-IPV scale showed good internal consistency and construct validity.

8.
Circ Genom Precis Med ; 13(3): e002670, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32469254

RESUMO

BACKGROUND: Genome-wide association studies provided many biological insights into coronary artery disease (CAD), but these studies were mainly performed in Europeans. Genome-wide association studies in diverse populations have the potential to advance our understanding of CAD. METHODS: We conducted 2 genome-wide association studies for CAD in the Japanese population, which included 12 494 cases and 28 879 controls and 2808 cases and 7261 controls, respectively. Then, we performed transethnic meta-analysis using the results of the coronary artery disease genome-wide replication and meta-analysis plus the coronary artery disease 1000 Genomes meta-analysis with UK Biobank. We then explored the pathophysiological significance of these novel loci and examined the differences in CAD-susceptibility loci between Japanese and Europeans. RESULTS: We identified 3 new loci on chromosome 1q21 (CTSS), 10q26 (WDR11-FGFR2), and 11q22 (RDX-FDX1). Quantitative trait locus analyses suggested the association of CTSS and RDX-FDX1 with atherosclerotic immune cells. Tissue/cell type enrichment analysis showed the involvement of arteries, adrenal glands, and fat tissues in the development of CAD. We next compared the odds ratios of lead variants for myocardial infarction at 76 genome-wide significant loci in the transethnic meta-analysis and a moderate correlation between Japanese and Europeans, where 8 loci showed a difference. Finally, we performed tissue/cell type enrichment analysis using East Asian-frequent and European-frequent variants according to the risk allele frequencies and identified significant enrichment of adrenal glands in the East Asian-frequent group while the enrichment of arteries and fat tissues was found in the European-frequent group. These findings indicate biological differences in CAD susceptibility between Japanese and Europeans. CONCLUSIONS: We identified 3 new loci for CAD and highlighted the genetic differences between the Japanese and European populations. Moreover, our transethnic analyses showed both shared and unique genetic architectures between the Japanese and Europeans. While most of the underlying genetic bases for CAD are shared, further analyses in diverse populations will be needed to elucidate variations fully.

9.
Exp Ther Med ; 19(4): 2973-2982, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32256783

RESUMO

Identification and screening of patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) is important to prevent liver cancer. Comprehensive antiviral treatments should follow three sequential steps: Hepatitis screening (step 1; examination of HB surface antigen and HCV antibody), medical examination (step 2; examination of HBV-DNA and/or HCV-RNA and performance of abdominal ultrasonography) and antiviral treatment (step 3). Patients who underwent these three steps were studied to determine effective information sources (factors) for raising awareness of comprehensive treatments. A total of 182 patients from 11 medical institutions were who were undergoing antiviral treatment were investigated. The number of patients who accessed each of the 18 information sources in each of the three steps and the percentage of these information sources that directly influenced the participants to make treatment-related decisions were calculated. 'Recommendation from a primary care physician' was the most common information source (64.3, 77.5, and 75.8% at steps 1, 2, and 3, respectively). 'Recommendation from a public health nurse (PHN),' 'recommendation from friends or family,' and 'recommendation from work colleagues' were the next most common human factors (3.3-19.8%). 'Recommendation from a primary care physician' had the greatest influence (76.9, 73.0, and 77.5% at steps 1, 2, and 3, respectively). 'Recommendation from a PHN' (50.0, 26.3 and 64.3%), 'recommendations from friends and family' (58.3, 38.9 and 58.3%), and 'recommendations from work colleagues' (33.3, 33.3 and 42.9%) were highly influential factors. Media such as TV commercial messages and programs also had high recognition, but were not directly influential. The findings of the present study indicated that recommendations from primary care physicians, friends, family and work colleagues influenced patients' decision-making regarding hepatitis screening, examination and treatment.

10.
Gastric Cancer ; 23(4): 725-733, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32048096

RESUMO

BACKGROUND: 5-aminolevulinic acid (5-ALA) has been utilized for cancer diagnosis as a fluorescence probe. We have reported the feasibility of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence for detecting lymph node (LN) metastasis in gastrointestinal malignancies. However, a major barrier to the fluorescence diagnosis has been that the evaluation has been highly dependent on the observers. In this study, we examined the validity of a developed device for automated detection without subjectivity. METHODS: Gastric cancer patients who received oral administration of 5-ALA (20 mg/kg) prior to surgery were enrolled. For a total of 323 LNs obtained from 64 patients, the diagnostic results of the device were compared to those of conventional histopathological examination based on hematoxylin-and-eosin-stained slides. The accuracy with the device was compared to that of stereoscopic detection with conventional fluorescence microscopy for 211 LNs from 42 patients. We used two types of image processing that we previously developed to eliminate autofluorescence of background tissues: differential and ratio methods. RESULTS: For detection of metastasis in 323 LNs, the areas under the receiver operating characteristic curves with the differential method and ratio method were 0.921 and 0.909, respectively. The sensitivity, specificity, and accuracy with the differential method were 78.0%, 96.8%, and 94.4%; while those with the ratio method were 78.0%, 96.1%, and 93.8%, respectively. In 211 LN analysis, the diagnostic accuracy with the device was comparable to that of stereoscopic examination. CONCLUSION: Our device for automated detection of LN metastasis using 5-ALA can be a useful tool for intraoperative diagnosis.

11.
Lancet Haematol ; 7(3): e218-e225, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978329

RESUMO

BACKGROUND: A previous dasatinib discontinuation (DADI) trial showed that 31 (49%) of 63 patients with chronic-phase chronic myeloid leukaemia who were treated with second-line or subsequent dasatinib could discontinue the drug safely. However, the safety and efficacy of discontinuing first-line dasatinib remains unclear. In this trial (the first-line DADI trial) we aimed to assess molecular relapse-free survival at 6 months after discontinuation of dasatinib in patients with chronic myeloid leukaemia who had been treated with first-line dasatinib and had maintained deep molecular response for at least 1 year. METHODS: The first-line DADI trial was a single-arm, multicentre, phase 2 trial done at 23 hospitals in Japan. Patients with newly diagnosed chronic-phase chronic myeloid leukaemia without hepatosplenomegaly and extramedullary mass, who received at least 24-month dasatinib treatment and had a sustained deep molecular response (defined as BCR-ABL1/ABL1 international scale ≤0·0069% in at least four successive samples spanning a 12 month period) were enrolled. Other eligibility criteria were an age of 15 years or older, an Eastern Cooperative Oncology Group performance status score of 0-2, and no primary organ dysfunction. The primary outcome was molecular relapse-free survival (also known as treatment-free remission) after discontinuation of dasatinib at 6 months and was analysed in all patients who completed the 12-month consolidation phase. Safety was assessed in all patients who received treatment. This study closed early due to accrual and is registered with the UMIN Clinical Trials Registry (UMIN000011099). FINDINGS: Between Sept 20, 2013 and July 12, 2016, 68 patients who had a deep molecular response after receiving first-line dasatinib for at least 24 months were enrolled and assigned to the consolidation phase. Nine patients were excluded during the consolidation phase and one patient was excluded after study completion because of meeting exclusion criteria. 58 patients discontinued dasatinib and were assessed. 32 (55%) of 58 patients had treatment-free remission at 6 months after dasatinib discontinuation, and median follow-up was 23·3 months (IQR 11·7-31·0). Treatment-free remission at 6 months was 55·2% (95% CI 43·7-69·6). No non-haematological adverse events worse than grade 2 occurred before dasatinib discontinuation. The most common haematological adverse event was anaemia (14 [21%] of 68 treated patients); three (4%) of 68 treated patients had grade 3 neutropenia and one (1%) had grade 4 lymphopenia. INTERPRETATION: Our findings suggest that dasatinib could be safely discontinued after first-line treatment in patients with chronic myeloid leukaemia who had received at least 36 months of therapy and sustained deep molecular response; however, further confirmation in larger trials is needed. FUNDING: Epidemiological and Clinical Research Information Network.


Assuntos
Dasatinibe/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Feminino , Seguimentos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Taxa de Sobrevida , Suspensão de Tratamento
12.
Jpn J Nurs Sci ; 17(1): e12264, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31161725

RESUMO

AIM: Smokers with HIV/AIDS have lower success of quitting smoking than smokers with other chronic diseases. However, there have been no studies investigating characteristics and outcomes of success of quitting smoking among people living with HIV compared to HIV-negative people who received smoking cessation therapy. In addition, there have been no studies that investigated factors associated with success of quitting smoking among people living with HIV in Japan. The aim of this study was to elucidate characteristics, outcomes and factors associated with the success of quitting smoking in people living with HIV. METHODS: We previously conducted a prospective cohort study on patients who received Japanese smoking cessation therapy (SCT), which consists of smoking cessation intervention five times with nurses' counseling over a 12-week period. Among them, we compared 77 HIV-positive male individuals and 323 HIV-negative male individuals with complications. RESULTS: Smokers with HIV had a larger number of cigarettes smoked per day, and higher scores of nicotine dependence and depression compared with the HIV-negative group. The HIV-positive group had a significantly lower success rate of quitting smoking than the HIV-negative group (35.1 vs. 47.7%, p = .046). The subjects living with HIV who had higher self-efficacy showed a significantly higher quit rate compared with those who had lower self-efficacy (odds ratio 9.99, p < .01). CONCLUSION: Smokers with HIV had characteristics that made it difficult for them to quit smoking. Increasing their self-efficacy of quitting smoking through nurses' counseling will lead to success of quitting smoking in HIV-positive smokers receiving the SCT.


Assuntos
Infecções por HIV/complicações , Autoeficácia , Abandono do Hábito de Fumar , Fumar/psicologia , Adulto , Aconselhamento , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Sci Rep ; 9(1): 16912, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729459

RESUMO

Deep-UV (DUV) excitation fluorescence microscopy has potential to provide rapid diagnosis with simple technique comparing to conventional histopathology based on hematoxylin and eosin (H&E) staining. We established a fluorescent staining protocol for DUV excitation fluorescence imaging that has enabled clear discrimination of nucleoplasm, nucleolus, and cytoplasm. Fluorescence images of metastasis-positive/-negative lymph nodes of gastric cancer patients were used for patch-based training with a deep neural network (DNN) based on Inception-v3 architecture. The performance on small patches of the fluorescence images was comparable with that of H&E images. Gradient-weighted class activation mapping analysis revealed the areas where the trained model identified metastatic lesions in the images containing cancer cells. We extended the method to large-size image analysis enabling accurate detection of metastatic lesions. We discuss usefulness of DUV excitation fluorescence imaging with the aid of DNN analysis, which is promising for assisting pathologists in assessment of lymph node metastasis.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Microscopia de Fluorescência , Redes Neurais de Computação , Algoritmos , Biópsia , Imunofluorescência , Humanos , Interpretação de Imagem Assistida por Computador , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Aprendizado de Máquina , Software
14.
Nihon Yakurigaku Zasshi ; 154(4): 171-177, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31597895

RESUMO

Recent outstanding progress in microscopic imaging technology and the advent of fluorescent probes have enabled us to visualize high spatiotemporal dynamics of intracellular molecules in living tissues. Here I introduce our research outcomes on functional fluorescence imaging of the heart especially for understanding the pathogenesis of cardiac arrhythmias. On the in situ Ca2+ imaging of perfused rat heart by rapid-scanning confocal microscopy, we found that burst emergence of intracellular Ca2+ waves evokes arrhythmogenic triggered activity and subsequent oscillatory depolarizations via the Na+-Ca2+ exchanger. Besides, impairment of Ca2+ release from the sarcoplasmic reticulum leads to emergence of Ca2+ waves and spatiotemporally inhomogeneous Ca2+ dynamics on systole, resulting in beat-to-beat Ca2+ alternans. Such alternating behaviors of Ca2+ dynamics are partly due to poor development of the transverse tubules, which are identified in murine atria and failing ventricular myocytes. In addition, impairment of the gap junctional communication via connexin 43 induced by dominant negative inhibition of neonatal rat ventricular myocyte monolayers results in generation of spiral wave reentry, suggesting the pivotal role of intercellular communications in genesis of arrhythmias. Furthermore, alterations in atrial histoanatomy, e.g., density and arrangements of myocytes and distribution of Cx43, could provide intrinsic arrhythmogenic bases of atrial fibrillation, which was revealed by combined optical imaging of the atria and precise histoanatomical examinations. In combination, fluorescence imaging of the living organisms provides indispensable information for unveiling functions and disease states.


Assuntos
Arritmias Cardíacas/fisiopatologia , Sinalização do Cálcio , Coração/diagnóstico por imagem , Imagem Óptica , Animais , Células Cultivadas , Átrios do Coração/diagnóstico por imagem , Miócitos Cardíacos/citologia , Ratos , Trocador de Sódio e Cálcio/metabolismo
15.
Cancer Med ; 8(12): 5524-5533, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31385432

RESUMO

Protoporphyrin IX-fluorescence measurement is a powerful in situ approach for cancer detection after oral/topical administration of 5-aminolevulinic acid. However, this approach has not been clinically established for breast cancer, probably due to insufficient delivery of 5-aminolevulinic acid to the mammary glands. In the present study, we directly exposed breast cancer cells to 5-aminolevulinic acid to assess their discrimination via protoporphyrin IX-fluorescence. Fluorescence intensity (FI) was measured in the human breast cancer cell lines MCF7 and MDA-MB-231 and breast epithelial cell line MCF10A by confocal microscopy and flow cytometry. After 5-aminolevulinic acid exposure for 2 hours, protoporphyrin IX-FI in MCF7 and MDA-MB-231 cells significantly increased with marked cell-to-cell variability, whereas that in MCF10A cells increased moderately. Combined exposure of the cancer cells to 5-aminolevulinic acid and Ko143, a specific inhibitor of ATP-binding cassette transporter G2, further increased protoporphyrin IX-FI and alleviated the cell-to-cell variability in MCF7 and MDA-MB-231 cells, indicating improvement in the reproducibility and accuracy for fluorescence-based cancer detection. The increased FI by combined administration of these two drugs was also demonstrated in cells obtained via fine needle aspiration from mouse xenograft models inoculated with MDA-MB-231 cells. Furthermore, a cutoff value for increased protoporphyrin IX-FI ratio, before and after exposure to these drugs, clearly discriminated between cancer and noncancer cells. Taken together, direct exposure to 5-aminolevulinic acid and Ko143 may be a promising strategy for efficient fluorescence-based detection of breast cancer cells ex vivo using fine needle aspiration.


Assuntos
Ácido Aminolevulínico/administração & dosagem , Biópsia por Agulha Fina/métodos , Neoplasias da Mama/diagnóstico , Dicetopiperazinas/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Protoporfirinas/metabolismo , Ácido Aminolevulínico/farmacocinética , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Dicetopiperazinas/farmacocinética , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Humanos , Células MCF-7 , Camundongos , Microscopia Confocal , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Sci Rep ; 9(1): 10745, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31341229

RESUMO

Deep-ultraviolet excitation fluorescence microscopy has enabled molecular imaging having an optical sectioning capability with a wide-field configuration and its usefulness for slide-free pathology has been shown in recent years. Here, we report usefulness of terbium ions as RNA-specific labeling probes for slide-free pathology with deep-ultraviolet excitation fluorescence. On excitation in the wavelength range of 250-300 nm, terbium ions emitted fluorescence after entering cells. Bright fluorescence was observed at nucleoli and cytoplasm while fluorescence became weak after RNA decomposition by ribonuclease prior to staining. It was also found that the fluorescence intensity at nucleoplasm increased with temperature during staining and that this temperature-dependent behavior resembled temperature-dependent hypochromicity of DNA due to melting. These findings indicated that terbium ions stained single-stranded nucleic acid more efficiently than double-stranded nucleic acid. We further combined terbium ions and DNA-specific dyes for dual-color imaging. In the obtained image, nucleolus, nucleoplasm, and cytoplasm were distinguished. We demonstrated the usefulness of dual-color imaging for rapid diagnosis of surgical specimen by showing optical sectioning of unsliced tissues. The present findings can enhance deep-ultraviolet excitation fluorescence microscopy and consequently expand the potential of fluorescence microscopy in life sciences.


Assuntos
Corantes Fluorescentes , Microscopia de Fluorescência/métodos , RNA/ultraestrutura , Térbio , Fluorescência , Humanos , Células MCF-7/ultraestrutura , RNA/metabolismo , Raios Ultravioleta
17.
FEBS Lett ; 593(18): 2535-2544, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31254349

RESUMO

Histopathology requires the expertise of specialists to diagnose morphological features of cells and tissues. Raman imaging can provide additional biochemical information to benefit histological disease diagnosis. Using a dietary model of nonalcoholic fatty liver disease in rats, we combine Raman imaging with machine learning and information theory to evaluate cellular-level information in liver tissue samples. After increasing signal-to-noise ratio in the Raman images through superpixel segmentation, we extract biochemically distinct regions within liver tissues, allowing for quantification of characteristic biochemical components such as vitamin A and lipids. Armed with microscopic information about the biochemical composition of the liver tissues, we group tissues having similar composition, providing a descriptor enabling inference of tissue states, contributing valuable information to histological inspection.


Assuntos
Aprendizado de Máquina , Hepatopatia Gordurosa não Alcoólica/patologia , Análise Espectral Raman , Animais , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Razão Sinal-Ruído
18.
J Phys Chem B ; 123(12): 2654-2661, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30830787

RESUMO

We investigated the use of narrowband Raman spectra for rapid label-free molecular imaging aimed at cell classification using principal component regression and linear discriminant analysis. In the classification of breast nontumorigenic epithelial and cancer cell lines, the classification accuracies using a spectral range of 100 cm-1 were equivalent to or better than that with using the fingerprint and high-wavenumber regions. Narrowing the Raman spectral range for analysis allows reduction of the charge-coupled device (CCD) pixels required for spectrum detection, resulting in the improvement of image acquisition speed with adequate classification accuracy. Our measurements revealed that the wavenumber region at 1397-1501 cm-1 can provide molecular information sufficient for cell classification without causing notable errors in the baseline-correction. A spectral resolution of ∼9 cm-1 was found to be sufficient to provide high accuracy in cell classification, which allowed us to apply pixel binning at the CCD readout for further acceleration of the imaging speed. As a result, the acquisition time for a 1200 × 1500 pixels Raman hyperspectral image at 1397-1501 cm-1 was reduced to 21 min. Under this condition, different cell lines were classified at accuracies higher than 90%. The presented approach will improve throughput of cell and tissue analysis and classification using Raman spectroscopy and extend practical uses of Raman imaging in biology and medicine.


Assuntos
Microscopia/métodos , Análise Espectral Raman/métodos , Linhagem Celular Tumoral , Humanos , Análise de Componente Principal , Análise de Regressão
19.
Sleep ; 42(6)2019 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-30810208

RESUMO

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Sono/genética , Grupo com Ancestrais do Continente Asiático/genética , Café/efeitos adversos , Feminino , Genótipo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fator de Transcrição PAX8/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Serina-Treonina Quinases/genética , Autorrelato
20.
Tob Induc Dis ; 17: 89, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31892919

RESUMO

INTRODUCTION: The 10-item version of the Questionnaire of Smoking Urges (QSU-brief) has demonstrated excellent reliability. However, the QSU-brief may be too long to use in clinical settings. We developed a new craving index called the Tobacco Craving Index (TCI) and investigated how closely the TCI grade is associated with success of quitting smoking in Japanese smoking cessation therapy (SCT) patients. METHODS: The TCI questionnaire consists of two items: the first question asks about the strength of tobacco craving on a 4-point scale, and the second question asks about the frequency of tobacco craving per day on a 4-point scale. We conducted a prospective cohort study of 85 participants who underwent the Japanese SCT at a Japanese smoking cessation clinic. We administered the QSU-brief and TCI at each of the 5 sessions during the 12-week SCT. RESULTS: Significant correlations were observed between the TCI grade and QSU-brief score (r=0.27, 0.55, 0.72, 0.58 and 0.68, at the five sessions). The change in mean TCI grade showed a similar trend as the change in mean QSU-brief score among the 43 patients who succeeded in quitting smoking and also among the 7 patients who failed to quit smoking by the last session. Both TCI and QSU-brief assessed after the second session were significantly associated with the smoking status at the last session. The area under the receiver operating characteristic curve for the success of quitting smoking in TCI grade was 0.615-0.881 at the 5 sessions, whereas it was 0.536-0.849 in QSU-brief score. CONCLUSIONS: The TCI can be used as a predictive tool for success of quitting smoking in the Japanese SCT. As the TCI consists of two questionnaire items, it can be easily administered in smoking cessation interventions.

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