scholarly journals Establishment of the MethyLight Assay for Assessing Aging, Cigarette Smoking, and Alcohol Consumption

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Kosuke Endo ◽  
Jiawei Li ◽  
Michio Nakanishi ◽  
Takashi Asada ◽  
Masahiro Ikesue ◽  
...  

The environmental factors such as aging, smoking, and alcohol consumption have been reported to influence DNA methylation (DNAm). However, the versatility of DNAm measurement by DNAm array systems is low in clinical use. Thus, we developed the MethyLight assay as a simple method to measure DNAm. In the present study, we isolated peripheral blood DNA from 33 healthy volunteers and selected cg25809905, cg02228185, and cg17861230 as aging, cg23576855 as smoking, and cg02583484 as alcohol consumption biomarkers. The predicted age by methylation rates of cg25809905 and cg17861230 significantly correlated with chronological age. In immortalized B-cells, DNAm rates of two sites showed a younger status than the chronological age of donor. On the other hand, the predicted age of the patients with myocardial infarction (MI) was not accelerated. The methylation rate of cg23576855 was able to discriminate the groups based on the smoking status. The DNAm rate of cg02583484 was reduced in subjects with habitual alcohol consumption compared to that of subjects without habitual alcohol consumption. In conclusion, our MethyLight assay system reconfirms that aging, smoking, and alcohol consumption influenced DNAm in peripheral blood in the Japanese. This MethyLight system will facilitate DNAm measurement in epidemiological and clinical studies.


2020 ◽  
Vol 4 (5) ◽  
pp. 893-905
Author(s):  
Boris A. Bartholdy ◽  
Xiahoua Wang ◽  
Xiao-Jie Yan ◽  
Marién Pascual ◽  
Manxia Fan ◽  
...  

Abstract Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF), and resting (RF) cellular fractions. Here, we found that these intraclonal circulating fractions share persistent DNA methylation signatures largely associated with the mutation status of the immunoglobulin heavy chain locus (IGHV) and their origins from distinct stages of differentiation of antigen-experienced B cells. Increased leukemic birth rate, however, showed a very limited impact on DNA methylation of circulating CLL fractions independent of IGHV mutation status. Additionally, DNA methylation heterogeneity increased as leukemic cells advanced from PF to RF in the peripheral blood. This frequently co-occurred with heterochromatin hypomethylation and hypermethylation of Polycomb-repressed regions in the PF, suggesting accumulation of longevity-associated epigenetic features in recently born cells. On the other hand, transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Several of these differentially expressed genes showed unique associations with clinical outcome not evident in the bulk clone, supporting the pathological and therapeutic relevance of studying intraclonal CLL fractions. We conclude that independent methylation and transcriptional landscapes reflect both preexisting cell-of-origin fingerprints and more recently acquired hallmarks associated with the life cycle of circulating CLL cells.



2018 ◽  
Vol 10 (2) ◽  
pp. 123-7
Author(s):  
Erika Diana Risanti ◽  
Aditya Kurniawan ◽  
Laila Wahyuningsih ◽  
Ery Kus Dwianingsih ◽  
Hanggoro Tri Rinonce ◽  
...  

BACKGROUND: Hypermethylation of RASSF1A and CDKN2A is one of epigenetic factor underlies nasopharyngeal carcinoma (NPC) development. Smoking behavior as an NPC’s risk factor causes aberrant DNA methylation. RASSF1A and CDKN2A promoter hypermethylation from peripheral blood cells correlates with smoking behavior. The use of body fluids including peripheral blood as a specimen for DNA methylation analyzes are widely developed, as less invasive method compared to the use of tissue biopsy. This study aims to observe the association between RASSF1A and CDKN2A methylation in peripheral blood and smoking behavioramong NPC patients.METHODS: Newly diagnosed NPC subjects were recruited from ear-nose-throat (ENT) outpatient clinic of Dr. Sardjito Hospital, Yogyakarta. DNA from buffycoat of 19 smokers and 20 non-smokers NPC’s patients were isolated. Bisulphite modification was applied to 500 ng of the isolated DNA. The methylation status was detected by MSP (methylation-specific polymerase chain reaction (PCR)). The association between smoking status and promoter hypermethylation was analysis using Chi-Square test.RESULTS: MSP analysis of RASSF1A showed that 68.42% smoker and 75% non-smoker NPC’s patients were methylated. MSP analysis of CDKN2A showed that 21.05% smoker and 25% non-smoker NPC’s patients were methylated. There was no association between smoking behavior with RASSF1A and CDKN2A methylation (p>0.05).CONCLUSION: Statistical analysis showed that smoking behavior is not associated with methylation of RASSF1A and CDKN2A among NPC’s patients.KEYWORDS: DNA methylation, CDKN2A, RASSF1A, Nasopharyngeal carcinoma, Smoking



Author(s):  
Ritienne Attard ◽  
Philip Dingli ◽  
Carine J. M. Doggen ◽  
Karen Cassar ◽  
Rosienne Farrugia ◽  
...  

Abstract Aim To determine the risk of myocardial infarction (MI) associated with pattern, frequency, and intensity of alcohol consumption, type of alcoholic beverage, and the combined effect of alcohol and smoking on risk of MI, inflammation, and lipid profile. Method A total of 423 cases with a first MI and 465 controls from the Maltese Acute Myocardial Infarction (MAMI) Study were analysed. Data was collected through an extensive interviewer-led questionnaire, along with measurements of various blood parameters. Medians and the Mann–Whitney test were used to assess effect of different drinking patterns, frequency, intensity, and smoking and drinking combinations on hs-CRP and lipid profile. Odds ratios, adjusted for the conventional risk factors of MI (AdjORs), were calculated as an estimate of the relative risk of MI. Results Regular alcohol consumption protected against MI [AdjOR 0.6 (95% CI 0.4–0.9)] while daily binge drinking increased risk [AdjOR 5.0 (95% CI 1.6–15.0)] relative to regular drinkers who did not binge drink. Whereas moderate weekly consumption of wine protected against MI, high weekly consumption of beer conveyed a deleterious effect. Alcohol consumption decreased risk of MI independent of smoking status. Frequent alcohol consumption was associated with higher HDL-, non-HDL-, total cholesterol and triglycerides, and lower hs-CRP. Total and HDL-cholesterol increased and BMI decreased with increasing quantity of weekly alcohol consumption relative to the non-regular drinkers. The effect of smoking on lipid profile and hs-CRP was less pronounced in current drinkers than in those who were non-regular drinkers. Conclusion The protective effect of alcohol consumption was dependent on the pattern, frequency, type, and intensity of alcohol consumed. Alcohol modified the effects of smoking on the lipid profile. Regular drinking attenuated the effect of smoking on hs-CRP and lipid profile.



2019 ◽  
Vol 8 (8) ◽  
pp. 822-832
Author(s):  
Claire Saucourt ◽  
Sandrine Vogt ◽  
Amandine Merlin ◽  
Christophe Valat ◽  
Anthony Criquet ◽  
...  


2011 ◽  
Vol 29 (9) ◽  
pp. 1133-1139 ◽  
Author(s):  
Carmen J. Marsit ◽  
Devin C. Koestler ◽  
Brock C. Christensen ◽  
Margaret R. Karagas ◽  
E. Andres Houseman ◽  
...  

Purpose Epigenetic alterations in tissues targeted for cancer play a causal role in carcinogenesis. Changes in DNA methylation in nontarget tissues, specifically peripheral blood, can also affect risk of malignant disease. We sought to identify specific profiles of DNA methylation in peripheral blood that are associated with bladder cancer risk and therefore serve as an epigenetic marker of disease susceptibility. Methods We performed genome-wide DNA methylation profiling on participants involved in a population-based incident case-control study of bladder cancer. Results In a training set of 112 cases and 118 controls, we identified a panel of 9 CpG loci whose profile of DNA methylation was significantly associated with bladder cancer in a masked, independent testing series of 111 cases and 119 controls (P < .0001). Membership in three of the most methylated classes was associated with a 5.2-fold increased risk of bladder cancer (95% CI, 2.8 to 9.7), and a model that included the methylation classification, participant age, sex, smoking status, and family history of bladder cancer was a significant predictor of bladder cancer (area under the curve, 0.76; 95% CI, 0.70 to 0.82). CpG loci associated with bladder cancer and aging had neighboring sequences enriched for transcription-factor binding sites related to immune modulation and forkhead family members. Conclusion These results indicate that profiles of epigenetic states in blood are associated with risk of bladder cancer and signal the potential utility of epigenetic profiles in peripheral blood as novel markers of susceptibility to this and other malignancies.



2018 ◽  
Author(s):  
Daniel L McCartney ◽  
Anna J Stevenson ◽  
Stuart J Ritchie ◽  
Rosie M Walker ◽  
Qian Zhang ◽  
...  

AbstractBackgroundGenome-wide DNA methylation (DNAm) profiling has allowed for the development of molecular predictors for a multitude of traits and diseases. Such predictors may be more accurate than the self-reported phenotypes, and could have clinical applications. Here, penalised regression models were used to develop DNAm predictors for body mass index (BMI), smoking status, alcohol consumption, and educational attainment in a cohort of 5,100 individuals. Using an independent test cohort comprising 906 individuals, the proportion of phenotypic variance explained in each trait was examined for DNAm-based and genetic predictors. Receiver operator characteristic curves were generated to investigate the predictive performance of DNAm-based predictors, using dichotomised phenotypes. The relationship between DNAm scores and all-cause mortality (n = 214 events) was assessed via Cox proportional-hazards models.ResultsThe DNAm-based predictors explained different proportions of the phenotypic variance for BMI (12%), smoking (60%), alcohol consumption (12%) and education (3%). The combined genetic and DNAm predictors explained 20% of the variance in BMI, 61% in smoking, 13% in alcohol consumption, and 6% in education. DNAm predictors for smoking, alcohol, and education but not BMI predicted mortality in univariate models. The predictors showed moderate discrimination of obesity (AUC=0.67) and alcohol consumption (AUC=0.75), and excellent discrimination of current smoking status (AUC=0.98). There was poorer discrimination of college-educated individuals (AUC=0.59).ConclusionsDNAm predictors correlate with lifestyle factors that are associated with health and mortality. They may supplement DNAm-based predictors of age to identify the lifestyle profiles of individuals and predict disease risk.List of abbreviationsDNAmDNA methylationBMIBody mass indexAUCArea under the curveCpGCytosine phosphate Guanine dinucleotideEWASEpigenome-wide association studyGS:SFHSGeneration Scotland: The Scottish family health studyLBC1936Lothian birth cohort 1936LASSOLeast absolute shrinkage and selector operatorHRHazard ratioCIConfidence intervalSTRADLStratifying resilience and depression longitudinally



1984 ◽  
Vol 23 (06) ◽  
pp. 317-319
Author(s):  
J. Novák ◽  
Y. Mazurová ◽  
J. Kubíček ◽  
J. Yižd’a ◽  
P. Kafka ◽  
...  

SummaryAcute myocardial infarctions were produced by ligature of the left frontal descending coronary artery in 9 dogs. The possibility of scintigraphic imaging with 99mTc-DMSA 4 hrs after intravenous administration was studied. The infarctions were 4, 24 and 48 hrs old. The in vivo scan was positive in only one dog with a 4-hr old infarction. The in vivo scans were confirmed by the analysis of the radioactivity in tissue samples. The accumulation of the radiopharmaceutical increased slightly in 48-hr old lesions; however, this increase was not sufficient for a positive scintigraphic finding. Thus, we do not recommend 99mTc-DMSA for clinical use in acute lesions.



1962 ◽  
Vol 41 (2) ◽  
pp. 211-218 ◽  
Author(s):  
K. Retiene ◽  
H. Ditschuneit ◽  
M. Fischer ◽  
K. Kopp ◽  
E. F. Pfeiffer

ABSTRACT Corticotrophin has been measured by using the corticotrophin-induced increase of corticosterone in adrenal venous blood of rats, the corticotrophin secretion of which has been blocked by preliminary injection of dexamethasone. Sensitivity and precision of this technique have not been higher than in the simpler procedure using corticosterone increase in peripheral blood. Single injection of dexamethasone on the other hand did not prevent release of endogenous corticotrophin following major surgery, required for canulation of the adrenal vein. In hypophysectomized rats corticotrophin can be measured by using adrenal venous blood. 0.05 mU corticotrophin (US-P-Standard) has been determined with an index of precision of λ = 0.13. The consistent relation between initial and elevated corticosterone level following corticotrophin in both peripheral and adrenal venous blood makes it highly unlikely that other modifications of this kind of assay will increase sensitivity.



2020 ◽  
Vol 17 (2) ◽  
pp. 291-320
Author(s):  
Asep Saefullah

Tulisan ini membahas fenomena penyebaran kitab-kitab cetak keaga­maan di Jawa Barat, khususnya di Sukabumi dan Cianjur. Jenis kitab ini biasanya menggunakan tulisan Arab dengan bahasa Sunda dan menggu­nakan aksara Pegon. Kitab-kitab cetak dari jenis-jenis itu diproduksi dan direproduksi, dan masih digunakan sampai hari ini. Oleh karena itu, fenomena ini dapat disebut sebagai “living tradition”. Pengumpulan data dilakukan dengan melacak dan merekam kitab-kitab yang diproduksi (disalin atau dikarang) dan direproduksi (dicetak atau digandakan) dengan metode seder­hana, yakni fotocopi dan pencetakan tradisional seperti stensil, sablon, dan "cetak toko". Tulisan ini bertujuan untuk memetakan dan merevisi kategorisasi kitab-kitab tersebut dari kajian terdahulu berdasarkan jenis karya, seperti karangan asli, tuqilan, terjemahan, syarḥ (penjelasan), khulasah (ringkasan) yang lain, dan juga berdasarkan bahasa dan aksara yang digunakan. Selain itu, tulisan ini juga mengamati lembaga-lembaga atau individu-individu yang masih mereproduksi buku-buku (kitab-kitab) keagamaan sederhana seperti perusahaan percetakan atau pesantren yang menerbitkan kitab-kitab tersebut. Pada akhir artikel ini, ada beberapa saran dalam upaya untuk melestarikan kitab-kitab cetak dan karya-karya tersebut.Kata kunci: kitab, jenis karya, pencetakan tradisional, Sunda, Pegon, Jawa Barat This paper discusses the phenomenon of the spreading of religious printed books (kitabs) in West Java, especially in Sukabumi and Cianjur, which are characterized by the use of Arabic writing in Sundanese (or known as Pegon script). The printed books (Kitabs) of those types are produced and reproduced, and are still used to this day. Therefore, this phenomenon can be called as a “living tradition”. Data collection was conducted by tracing and recording religious books (kitabs) that are pro-duced (rewritten or compossed) and reproduced (printed or duplicated) with a simple method, known as photocopying and traditional printing such as stencils, screen printing, and “shop printing”. This paper aims to map and revise the categorization of these Kitabs from previous studies based on the types of works including original essays, tuqilan (quotations), translation, sharh (explanation), khulaṣah (summary), or the other, and also based on the language and the script used. In addition, this paper also observes the institutions or individuals that are still reproducing these printed religious books such as the printing company or pesantren that publish such kitabs. At the end of this article, there are some suggestions in attempts to preserve those printed kitabs and the works.Keywords: Kitabs, type of work, traditional printing, Sunda, Pegon, West Java



Sign in / Sign up

Export Citation Format

Share Document