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1.
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.

2.
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.

3.
Sci Rep ; 9(1): 10745, 2019 Jul 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.

4.
Jpn J Nurs Sci ; 2019 Jun 03.
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.

5.
FEBS Lett ; 593(18): 2535-2544, 2019 Sep.
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.

6.
J Phys Chem B ; 123(12): 2654-2661, 2019 Mar 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.

7.
Sleep ; 42(6)2019 Jun 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.

8.
Nat Commun ; 9(1): 5278, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30538244

RESUMO

Regulation of intracellular pH is critically important for many cellular functions. The quantification of proton extrusion in different types of cells and physiological conditions is pivotal to fully elucidate the mechanisms of pH homeostasis. Here we show the use of gold nanoparticles (AuNP) to create a high spatial resolution sensor for measuring extracellular pH in proximity of the cell membrane. We test the sensor on HepG2 liver cancer cells and MKN28 gastric cancer cells before and after inhibition of Na+/H+ exchanger. The gold surface conjugation strategy is conceived with a twofold purpose: i) to anchor the AuNP to the membrane proteins and ii) to quantify the local pH from AuNP using surface enhanced Raman spectroscopy (SERS). The nanometer size of the cell membrane anchored sensor and the use of SERS enable us to visualize highly localized variation of pH induced by H+ extrusion, which is particularly upregulated in cancer cells.


Assuntos
Espaço Extracelular/química , Espaço Extracelular/virologia , Ouro/química , Nanopartículas Metálicas/química , Membrana Celular/química , Membrana Celular/metabolismo , Espaço Extracelular/metabolismo , Células Hep G2 , Humanos , Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Sódio/metabolismo , Análise Espectral Raman
9.
Sci Rep ; 8(1): 14671, 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30279495

RESUMO

Understanding the viability of the ischemic myocardial tissue is a critical issue in determining the appropriate surgical procedure for patients with chronic heart failure after myocardial infarction (MI). Conventional MI evaluation methods are; however, preoperatively performed and/or give an indirect information of myocardial viability such as shape, color, and blood flow. In this study, we realize the evaluation of MI in patients undergoing cardiac surgery by Raman spectroscopy under label-free conditions, which is based on intrinsic molecular constituents related to myocardial viability. We identify key signatures of Raman spectra for the evaluation of myocardial viability by evaluating the infarct border zone myocardium that were excised from five patients under surgical ventricular restoration. We also obtain a prediction model to differentiate the infarcted myocardium from the non-infarcted myocardium by applying partial least squares regression-discriminant analysis (PLS-DA) to the Raman spectra. Our prediction model enables identification of the infarcted tissues and the non-infarcted tissues with sensitivities of 99.98% and 99.92%, respectively. Furthermore, the prediction model of the Raman images of the infarct border zone enabled us to visualize boundaries between these distinct regions. Our novel application of Raman spectroscopy to the human heart would be a useful means for the detection of myocardial viability during surgery.

10.
Acta Histochem Cytochem ; 51(3): 101-110, 2018 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-30083018

RESUMO

Raman scattering of a cell conveys the intrinsic information inherent to chemical structures of biomolecules. The spectroscopy of Raman scattering, or Raman spectroscopy, allows label-free and quantitative molecular sensing of a biological sample in situ without disruption. For the last five decades Raman spectroscopy has been widely utilized in biological research fields. However, it is just within the latest decade that molecular imaging and discrimination of living cells and tissues have become practically available. Here we overview recent progress in Raman spectroscopy and its application to life sciences. We discuss imaging of functional molecules in living cells and tissues; e.g., cancer cells and ischemic or infarcted hearts, together with a number of studies in the biomedical fields. We further explore comprehensive understandings of a complex spectrum by multivariate analysis for, e.g., accurate peripheral nerve detection, and characterization of the histological differences in the healing process of myocardial infarct. Although limitations still remain, e.g., weakness of the scattering intensity and practical difficulty in comprehensive molecular analysis, continuous progress in related technologies will allow wider use of Raman spectroscopy for biomedical applications.

11.
Clin Lymphoma Myeloma Leuk ; 18(5): 353-360.e1, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29610029

RESUMO

INTRODUCTION: We previously reported an interim analysis of the DADI (dasatinib discontinuation) trial. The results showed that 48% of patients with chronic myeloid leukemia in the chronic phase who maintained a deep molecular response (DMR) for ≥ 1 year could discontinue second- or subsequent-line dasatinib treatment safely at a median follow-up of 20 months. However, the results from longer follow-up periods would be much more useful from a clinical perspective. PATIENTS AND METHODS: The DADI trial was a prospective, multicenter trial conducted in Japan. After confirming a stable DMR for ≥ 1 year, dasatinib treatment subsequent to imatinib or nilotinib was discontinued. After discontinuation, the loss of DMR (even of 1 point) was defined as stringent molecular relapse, thereby triggering therapy resumption. The predictive factors of treatment-free remission (TFR) were analyzed. RESULTS: The median follow-up period was 44.0 months (interquartile range, 40.5-48.0 months). The estimated overall TFR rate at 36 months was 44.4% (95% confidence interval, 32.0%-56.2%). Only 2 patients developed a molecular relapse after the 1-year cutoff point. The presence of imatinib resistance was a significant risk factor for molecular relapse. Moreover, high natural killer cell and low γδ+ T-cell and CD4+ regulatory T-cell (CD25+CD127low) counts before discontinuation correlated significantly with successful therapy discontinuation. CONCLUSION: These findings suggest that discontinuation of second- or subsequent-line dasatinib after a sustained DMR of ≥ 1 year is feasible, especially for patients with no history of imatinib resistance. In addition, the natural killer cell count was associated with the TFR.

12.
Int J Nurs Pract ; 24(4): e12647, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29573128

RESUMO

AIMS: To identify the strength of self-efficacy during 12-week smoking cessation therapy (SCT) that consisted of 5 sessions and its association with the success of smoking cessation at the end of SCT. BACKGROUND: Few studies showed to what level self-efficacy should be reinforced to facilitate success in smoking cessation. DESIGN: Prospective cohort study. METHODS: We enrolled 488 smokers who received SCT from 6 Japanese smoking cessation clinics between October 2008 and October 2014. In each smoker, the self-efficacy of quitting smoking was assessed at each session of SCT. The association of the strength of self-efficacy with the success of smoking cessation was investigated by logistic regression analysis adjusting for age, gender, having a present illness, prescription, and nicotine dependence score. RESULTS: The self-efficacy of the 398 abstainers was significantly higher than that of the 90 nonabstainers at the first to fifth sessions of the SCT (P < .001 each). Participants with self-efficacy scores of greater than 60% were significantly more likely to attain abstinence than those with scores of 40% and less. CONCLUSION: During SCT, nurses' counselling to maintain patients' self-efficacy scores of smoking cessation in the range from 61% to 100% may be important for assisting patients in achieving smoking cessation.


Assuntos
Autoeficácia , Abandono do Hábito de Fumar , Estudos de Coortes , Aconselhamento , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade
13.
J Epidemiol ; 28(10): 420-427, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-29479003

RESUMO

BACKGROUND: Recent improvements in 5-year survival of breast cancer have been reported in Japan and other countries. Though the number of long-term breast cancer survivors has been increasing, recent improvements in 10-year survival have not been reported. Moreover, the degree of improvement according to age and disease stage remains unclear. METHODS: We calculated long-term survival using data on breast cancer diagnosed from 1993 through 2006 from six prefectural population-based cancer registries in Japan. The recent increase in 10-year relative survival was assessed by comparing the results of period analysis in 2002-2006 with the results of cohort analysis in 1993-1997. We also conducted stratified analyses by age group (15-34, 35-49, 50-69, and 70-99 years) and disease stage (localized, regional, and distant). RESULTS: A total of 63,348 patients were analysed. Ten-year relative survival improved by 2.4% (76.9% vs 79.3%) from 1993 through 2006. By age and stage, 10-year relative survival clearly improved in the age 35-49 years (+2.9%; 78.1% vs 81.0%), 50-69 years (+2.8%; 75.2% vs 78.0%) and regional disease (+3.4%; 64.9% vs 68.3%). In contrast, the degree of improvement was small in the age 15-34 years (+0.1%; 68.2% vs 68.3%), 70-99 years (+1.0%; 87.6% vs 88.6%), localized disease (+1.1%; 92.6% vs 93.7%) and distant metastasis (+0.9%; 13.8% vs 14.7%). CONCLUSIONS: These population-based cancer registry data show that 10-year relative survival improved 2.4% over this period in Japan. By age and stage, improvement in the age 15-34 years and distant metastasis was very small, which suggests the need for new therapeutic strategies in these patients.

14.
Sci Rep ; 8(1): 1493, 2018 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-29367735

RESUMO

Coffee is one of the most widely consumed beverages worldwide, and its role in human health has received much attention. Although genome-wide association studies (GWASs) have investigated genetic variants associated with coffee consumption in European populations, no such study has yet been conducted in an Asian population. Here, we conducted a GWAS to identify common genetic variations that affected coffee consumption in a Japanese population of 11,261 participants recruited as a part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. Coffee consumption was collected using a self-administered questionnaire, and converted from categories to cups/day. In the discovery stage (n = 6,312), we found 2 independent loci (12q24.12-13 and 5q33.3) that met suggestive significance (P < 1 × 10-6). In the replication stage (n = 4,949), the lead variant for the 12q24.12-13 locus (rs2074356) was significantly associated with habitual coffee consumption (P = 2.2 × 10-6), whereas the lead variant for the 5q33.3 locus (rs1957553) was not (P = 0.53). A meta-analysis of the discovery and replication populations, and the combined analysis using all subjects, revealed that rs2074356 achieved genome-wide significance (P = 2.2 × 10-16 for a meta-analysis). These findings indicate that the 12q24.12-13 locus is associated with coffee consumption among a Japanese population.

15.
Sci Rep ; 8(1): 785, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29335418

RESUMO

The Tsuruoka Metabolomics Cohort Study included subjects aged 35-74 years from participants in annual health check-up programs in Tsuruoka, Japan. The gender-specific associations of early age-related macular degeneration (AMD) with systemic and genetic factors was assessed cross-sectionally. Of these, 3,988 subjects had fundus photographs of sufficient quality, and early AMD was present in 12.3% and 10.3% of men and women, respectively. In men, higher levels of high-density lipoprotein cholesterol and lower levels of triglycerides were associated with increased odds of having early AMD after adjusting for potential risk factors (for each 1 mmol/L increase, odds ratio [OR]: 1.61 and 0.78, 95% confidence interval [CI]: 1.17-2.23 and 0.64-0.96, respectively). In women, higher levels of total cholesterol and low-density lipoprotein cholesterol were associated with increased risk of having early AMD (OR: 1.21 and 1.26, 95% CI: 1.01-1.44 and 1.03-1.53, respectively). Sub-analysis demonstrated that women with ARMS2 A69S polymorphisms had a stronger risk for early AMD (OR: 3.25, 95% CI: 2.10-5.04) than men (OR: 1.65, 95% CI: 1.02-2.69). Differential associations of early AMD with both systemic and genetic factors by sex were demonstrated in a Japanese cohort, which suggests that disease process of early AMD could be different by sex.


Assuntos
Degeneração Macular/patologia , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Fator H do Complemento/genética , Feminino , Humanos , Japão , Modelos Logísticos , Degeneração Macular/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Fatores de Risco , Fatores Sexuais
16.
Gastric Cancer ; 21(3): 573-577, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28875341

RESUMO

BACKGROUND: Endoscopic findings have now become nearly as detailed as histopathological findings. Thus, one-to-one correspondence and precise feedback of histopathological findings is very desirable but may be very difficult to accomplish. We describe a systematic process called the Kyoto One-to-One Correspondence Method (the KOTO Method) that allows detailed adjustments of endoscopic findings to match histopathological findings. METHODS AND RESULTS: By comparing endoscopic and stereoscopic images of the gastric mucosa, we could obtain one-to-one correspondence between endoscopic images and equivalent histology in 44 of 47 fields. CONCLUSIONS: The histological structure of gastric cancers of the same histological subtype may not be similar. One-to-one correspondence between endoscopic images and gastric mucosal histology (histopathology-oriented correspondence) will improve endoscopic diagnosis and provide more useful information for pathological diagnosis.


Assuntos
Citodiagnóstico/métodos , Endoscopia , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Humanos , Estudos Retrospectivos
17.
J Epidemiol ; 28(4): 185-193, 2018 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-29176272

RESUMO

BACKGROUND: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. METHODS: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. RESULTS: The ALDH2 Glu/Lys or Lys/Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g/day was -2.49 mg/dL (95% confidence interval [CI], -3.85 to -1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His/His + ALDH2 Glu/Lys or Lys/Lys groups (-3.24 mg/dL, 95% CI, -5.03 to -1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His/His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu/Lys or Lys/Lys groups was replicated. CONCLUSIONS: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.


Assuntos
Álcool Desidrogenase/genética , Consumo de Bebidas Alcoólicas/sangue , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Lipoproteínas LDL/sangue , Polimorfismo Genético/genética , Triglicerídeos/sangue , Adulto , Idoso , Alelos , Estudos de Coortes , Genótipo , Humanos , Japão , Masculino , Pessoa de Meia-Idade
18.
J Epidemiol ; 28(2): 75-80, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29109365

RESUMO

BACKGROUND: Medical circumstances in Japanese patients with cancer of the corpus uteri have greatly changed since the late 1990s, including the introduction of concomitant therapy with taxane and platinum. We evaluated changes in survival rates for this cancer following these advances by analyzing data from population-based cancer registries in Japan. METHODS: Data were available for 8562 cases of cancer of the corpus uteri from six prefectural cancer registries. We defined the two periods of 1993-2000 (1st period) and 2001-2006 (2nd period). Relative survival (RS) in each period was calculated to assess changes using an excess mortality model, with adjustment for age group (15-54, 55-69, and 70-99 years), extent of disease (localized, regional, and distant), and histological subtype. RESULTS: Overall 5-year RS improved from 77.7% in the 1st period to 80.2% in the 2nd period, with an excess hazard ratio (EHR) of 0.785 (95% confidence interval [CI], 0.705-0.873). Five-year RS significantly improved in the group aged 55-69 years, in all groups by extent of disease, and in the endometrioid adenocarcinoma group. In particular, 5-year RS significantly improved in patients with endometrioid adenocarcinoma, from 84.5% to 89.7%, with an EHR of 0.698 (95% CI, 0.560-0.870). CONCLUSION: Overall 5-year RS for cancer of the corpus uteri in Japan improved from the 1990s to early 2000s. These improvements might have been aided by the comprehensive medical development of management for this cancer, including the spread of concomitant therapy with taxane and platinum as a standard adjuvant chemotherapy in the early 2000s.


Assuntos
Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Sistema de Registros , Taxa de Sobrevida/tendências , Adulto Jovem
19.
Br J Nutr ; 118(6): 463-472, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28980890

RESUMO

Although higher circulating levels of oestrogen are related to postmenopausal breast cancer risk, limited information is available regarding effects of diet on endogenous oestrogen. Thus, we examined associations between macronutrient intakes and serum oestrogen with consideration of polymorphisms in oestrogen-metabolising genes. In this cross-sectional study, 784 naturally menopaused Japanese women aged 47-69 years were selected from participants of the Japan Multi-Institutional Collaborative Cohort Study. We documented dietary intakes, measured serum concentrations of oestrone (E1) and oestradiol (E2) and genotyped polymorphisms in oestrogen-metabolising CYP19A1 (rs4441215 and rs936306) and HSD17B1 (rs605059) genes. Trends and interactions were examined using linear regression models. In addition, we calculated the ratios of the oestrogen concentrations of the second to the highest quartiles (Q2-Q4) of dietary intake to those of the lowest quartiles (Q1). After adjustment for potential confounders, E2 was significantly associated with intake of carbohydrate and noodles; ratios of Q4 v. Q1 were 1·15 (95 % CI 1·04, 1·28) and 1·15 (95 % CI 1·04, 1·26), respectively. In contrast, E2 levels were inversely associated with intake of total energy, SFA and n-3 highly unsaturated fatty acids (n-3 HUFA); ratios of Q4 v. Q1 were 0·90 (95 % CI 0·82, 0·99), 0·89 (95 % CI 0·81, 0·98) and 0·91 (95 % CI 0·83, 1·00), respectively. In stratified analysis by polymorphisms, the rs605059 genotype of HSD17B1 significantly modified associations of E2 with intake of n-3 HUFA and fish; the associations were limited to those with the CC genotype. Macronutrient intakes were associated with serum E2 level, and these associations may be modified by HSD17B1 polymorphism in postmenopausal women.


Assuntos
Aromatase/genética , Grupo com Ancestrais do Continente Asiático/genética , Dieta , Estradiol Desidrogenases/genética , Estrogênios/sangue , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/sangue , Idoso , Animais , Estudos Transversais , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Proteínas na Dieta/administração & dosagem , Estradiol/sangue , Ácidos Graxos/administração & dosagem , Ácidos Graxos/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/sangue , Feminino , Peixes , Técnicas de Genotipagem , Humanos , Japão , Estilo de Vida , Modelos Lineares , Pessoa de Meia-Idade , Alimentos Marinhos , Inquéritos e Questionários
20.
J Histochem Cytochem ; 65(11): 655-667, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28903013

RESUMO

Surviving Purkinje fibers in myocardial infarct are regarded as an important substrate in arrhythmogenesis. However, poorly understood are functional properties of Purkinje fibers in the infarcted heart. We sought to visualize intracellular Ca2+ ([Ca2+]i) dynamics of Purkinje fiber networks in the mouse myocardial infarct. Using 3- to 4-day-old or 7- to 9-day-old infarcted hearts after the left coronary-artery ligation corresponding, respectively, to acute or healing phase, we conducted rapid fluo4-fluorescence imaging on the endocardial surface of the left ventricular septum by macro-zoom fluorescence microscopy and rapid-scanning confocal microscopy. In contrast with the intact heart, where uniform Ca2+ transients propagated rapidly, the infarcted heart exhibited slow, non-uniform impulse propagations. On confocal microscopy, Purkinje fibers in the peri-infarct zone exhibited non-uniform [Ca2+]i dynamics: beat-to-beat alternans of the Ca2+ transient amplitude in and among the individual fibers, whereas the intact fibers exhibited uniform Ca2+ transients. Such non-uniform [Ca2+]i dynamics were more conspicuous in the acute infarcted hearts than in the healing ones. In accordance with [Ca2+]i dynamics, fixed fluo4-loaded heart preparations exhibited definitive connexin-40 plaques in the peri-infarct Purkinje fibers, whereas the subjacent myocardium presented coagulative necrosis and granulation tissues, respectively. The surviving Purkinje fibers in the peri-infarct zone exhibited non-uniform [Ca2+]i dynamics, which may lead to arrhythmogenesis.


Assuntos
Cálcio/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Ramos Subendocárdicos/metabolismo , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Confocal , Microscopia de Fluorescência
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