Methylation patterns in sentinel genes in peripheral blood cells of heavy smokers: Influence of cruciferous vegetables in an intervention study.

Science.gov (United States)

Scoccianti, Chiara; Ricceri, Fulvio; Ferrari, Pietro; Cuenin, Cyrille; Sacerdote, Carlotta; Polidoro, Silvia; Jenab, Mazda; Hainaut, Pierre; Vineis, Paolo; Herceg, Zdenko

2011-09-01

Changes in DNA methylation patterns are a hallmark of tobacco-induced carcinogenesis. We have conducted a randomized 4-week intervention trial to investigate the effects of three dietary regimens to modify DNA methylation patterns in peripheral white blood cells of heavy smokers. A group of 88 smokers were randomly assigned to and distributed among three diets, including (1) normal isocaloric diet (balanced in fruits and vegetables), according to international guidelines; (2) a diet enriched in flavonoids and isothiocyanates (particularly cruciferous vegetables); (3) a regimen consisting of diet 1 supplemented with flavonoids (green tea and soy products). Methylation patterns were analyzed by pyrosequencing in LINE1 (Long Interspersed DNA Elements), RASSF1A, ARF and CDKN2a (tumor suppressor genes), MLH1 (mismatch DNA repair) and MTHFR (folate metabolism). Three distinct patterns of methylation were observed. In LINE1, methylation showed a small but reproducible increase with all three regimens. MTHFR was constitutively methylated with no significant modulation by diets. The four other loci showed low basal levels of methylation with no substantial change after intervention. These data suggest that the isocaloric diet may stabilize global epigenetic (LINE1 DNA methylation) patterns in peripheral white blood cells but does not provide evidence for methylation changes in specific genes associated with this short-term dietary intervention.

White Blood Cell Counts and Malaria

National Research Council Canada - National Science Library

McKenzie, F. E; Prudhomme, Wendy A; Magill, Alan J; Forney, J. R; Permpanich, Barnyen; Lucas, Carmen; Gasser, Jr., Robert A; Wongsrichanalai, Chansuda

2005-01-01

White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999...

Rapid white blood cell detection for peritonitis diagnosis

Science.gov (United States)

Wu, Tsung-Feng; Mei, Zhe; Chiu, Yu-Jui; Cho, Sung Hwan; Lo, Yu-Hwa

2013-03-01

A point-of-care and home-care lab-on-a-chip (LoC) system that integrates a microfluidic spiral device as a concentrator with an optical-coding device as a cell enumerator is demonstrated. The LoC system enumerates white blood cells from dialysis effluent of patients receiving peritoneal dialysis. The preliminary results show that the white blood cell counts from our system agree well with the results from commercial flow cytometers. The LoC system can potentially bring significant benefits to end stage renal disease (ESRD) patients that are on peritoneal dialysis (PD).

Extraction of Nucleolus Candidate Zone in White Blood Cells of Peripheral Blood Smear Images Using Curvelet Transform

Directory of Open Access Journals (Sweden)

Ramin Soltanzadeh

2012-01-01

Full Text Available The main part of each white blood cell (WBC is its nucleus which contains chromosomes. Although white blood cells (WBCs with giant nuclei are the main symptom of leukemia, they are not sufficient to prove this disease and other symptoms must be investigated. For example another important symptom of leukemia is the existence of nucleolus in nucleus. The nucleus contains chromatin and a structure called the nucleolus. Chromatin is DNA in its active form while nucleolus is composed of protein and RNA, which are usually inactive. In this paper, to diagnose this symptom and in order to discriminate between nucleoli and chromatins, we employ curvelet transform, which is a multiresolution transform for detecting 2D singularities in images. For this reason, at first nuclei are extracted by means of K-means method, then curvelet transform is applied on extracted nuclei and the coefficients are modified, and finally reconstructed image is used to extract the candidate locations of chromatins and nucleoli. This method is applied on 100 microscopic images and succeeds with specificity of 80.2% and sensitivity of 84.3% to detect the nucleolus candidate zone. After nucleolus candidate zone detection, new features that can be used to classify atypical and blast cells such as gradient of saturation channel are extracted.

Multiple loci are associated with white blood cell phenotypes.

Directory of Open Access Journals (Sweden)

Michael A Nalls

2011-06-01

Full Text Available White blood cell (WBC count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2, including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across

Tissue engineering of bladder using vascular endothelial growth factor gene-modified endothelial progenitor cells.

Science.gov (United States)

Chen, Bai-Song; Xie, Hua; Zhang, Sheng-Li; Geng, Hong-Quan; Zhou, Jun-Mei; Pan, Jun; Chen, Fang

2011-12-01

This study assessed the use of vascular endothelial growth factor (VEGF) gene-modified endothelial progenitor cells (EPCs) seeded onto bladder acellular matrix grafts (BAMGs), to enhance the blood supply in tissue-engineered bladders in a porcine model. Autologous porcine peripheral EPCs were isolated, cultured, expanded, characterized, and modified with the VEGF gene using an adenovirus vector. The expression of VEGF was examined using reverse transcriptase polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA). VEGF gene modified EPCs were seeded onto BAMG and cultured for 3 days before implantation into pigs for bladder tissue engineering. A partial bladder cystectomy was performed in 12 pigs. The experimental group (6 pigs) received VEGF gene-modified EPC-seeded BAMG. The control group (6 pigs) received BAMG without seeded EPCs. The resulting tissue-engineered bladders were subject to a general and histological analysis. Microvessel density (MVD) was assessed using immunohistochemistry. The ex vivo transfection efficiency of EPCs was greater than 60%-70% when concentrated adenovirus was used. The genetically modified cells expressed both VEGF and green fluorescent protein (GFP). Scanning electron microscopy (SEM) and Masson's trichrome staining of cross sections of the cultured cells seeded to BAMG showed cell attachment and proliferation on the surface of the BAMG. Histological examination revealed bladder regeneration in a time-dependent fashion. Significant increases in MVD were observed in the experimental group, in comparison with the control group. VEGF-modified EPCs significantly enhanced neovascularization, compared with BAMG alone. These results indicate that EPCs, combined with VEGF gene therapy, may be a suitable approach for increasing blood supply in the tissue engineering of bladders. Thus, a useful strategy to achieve a tissue-engineered bladder is indicated.

Blood lead levels, iron metabolism gene polymorphisms and homocysteine: a gene-environment interaction study.

Science.gov (United States)

Kim, Kyoung-Nam; Lee, Mee-Ri; Lim, Youn-Hee; Hong, Yun-Chul

2017-12-01

Homocysteine has been causally associated with various adverse health outcomes. Evidence supporting the relationship between lead and homocysteine levels has been accumulating, but most prior studies have not focused on the interaction with genetic polymorphisms. From a community-based prospective cohort, we analysed 386 participants (aged 41-71 years) with information regarding blood lead and plasma homocysteine levels. Blood lead levels were measured between 2001 and 2003, and plasma homocysteine levels were measured in 2007. Interactions of lead levels with 42 genotyped single-nucleotide polymorphisms (SNPs) in five genes ( TF , HFE , CBS , BHMT and MTR ) were assessed via a 2-degree of freedom (df) joint test and a 1-df interaction test. In secondary analyses using imputation, we further assessed 58 imputed SNPs in the TF and MTHFR genes. Blood lead concentrations were positively associated with plasma homocysteine levels (p=0.0276). Six SNPs in the TF and MTR genes were screened using the 2-df joint test, and among them, three SNPs in the TF gene showed interactions with lead with respect to homocysteine levels through the 1-df interaction test (plead levels. Blood lead levels were positively associated with plasma homocysteine levels measured 4-6 years later, and three SNPs in the TF gene modified the association. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Can intrinsic human tissue radiosensitivity be correlated with late responding gene RNA expression in white blood cells using a 96 gene micro-array?

International Nuclear Information System (INIS)

Schmidt, D.; Streeter, O.; Dagliyan, G.; Hill, C.K.; Williams-Hill, D.M.

2003-01-01

Radiation is widely used in the treatment of cancers. It is generally believed there is a sigmoid relationship between radiation dose and probability of cure. There is also a sigmoid relationship between radiation dose and normal tissue response. Generally total radiation dose to a tumor is limited by normal tissue tolerance. It has been postulated that up to 70% of inter-individual differences in radiosensitivity may be due to genetic predisposition (Tureson I. Et al, IJROBP, 1996;36:1065). However, to date, clinicians have no way of estimating or predicting an individual's normal tissue response to radiation exposure. Thus the prescribed dose cannot be tailored to an individuals actual expected response but is an empirically derived compromise based on experience. Although a number of studies using cellular techniques have shown that human cell radiosensitivity can be measured, none of these can be performed quick enough to be used in the clinic. In this study we are looking at gene expression that occurs some 24 hours after an exposure compared to expression before any exposure in peripheral white blood cells from patients undergoing radiotherapy for various tumors. The patients will be followed for overt radiation sensitivity by standard criteria by clinicians in the Department. The main aims are: does RNA expression level in a 96 gene micro-array vary before and after radiation and do these changes in RNA expression correlate with the objective measurements of acute radiation response observed by the clinicians in the patients. The USC IRB recently approved the protocol and human consent for this study to enter 50 patients in the next 12 months using mostly head and neck and endometrial cancer patients where we can get a normal tissue sample to examine as well as the blood sample. We will present the rationale, protocol, methods and early results in detail

The study of the structures of the white blood cells using pattern recognition technique

International Nuclear Information System (INIS)

Arquisa, M.

1976-03-01

It is aimed that through machine recognition, a significant quantitative description of the white blood cells be obtained. This technique will give the characterization of the normal and abnormal white blood cells which may eventually lead to exact and efficient blood examinations and to the possibility of using white blood cells as an effective biological monitor in the assessment of radiation damage and other pathological disorders. Described are the preparation of blood stains and staining procedure with Giemsa and Wright stains, photomicrography of white blood cells with the use of Kodak Dektol Developer and Kodak Acid-Bath Fixer. The film rolls were then scanned. The scanner is used to scan photographic transparencies of white blood cells. This instrument gathers information and converts cell features such as size, shape, ash and granulation into a series of parameters whose values are descriptive of the minute but essential structural characteristics of the cells. From July 1 -December 31, 1975, a total of 51 blood smears were collected and stained. From these blood samples, a total of 103 neutrophils, 30 lymphocytes and 12 monocytes were added to the film library

Red flag on the white reporter: a versatile insulator abuts the white gene in Drosophila and is omnipresent in mini-white constructs

OpenAIRE

Chetverina, Darya; Savitskaya, Ekaterina; Maksimenko, Oksana; Melnikova, Larisa; Zaytseva, Olga; Parshikov, Alexander; Galkin, Alexander V.; Georgiev, Pavel

2007-01-01

Much of the research on insulators in Drosophila has been done with transgenic constructs using the white gene (mini-white) as reporter. Hereby we report that the sequence between the white and CG32795 genes in Drosophila melanogaster contains an insulator of a novel kind. Its functional core is within a 368 bp segment almost contiguous to the white 3′UTR, hence we name it as Wari (white-abutting resident insulator). Though Wari contains no binding sites for known insulator proteins and does ...

[Subchronic toxicity test of genetically modified rice with double antisense starch-branching enzyme gene].

Science.gov (United States)

Li, Min; Piao, Jianhua; Yang, Xiaoguang

2010-07-01

To observe the sub-chronic toxic effects of the genetically modified rice with double antisense SBE gene. Based on gender and weight, weanling Wistar rats were randomly sorted into five groups: non-genetically modified rice group (group A), genetically modified rice group (group B), half genetically modified rice group (group C), quarter genetically modified rice group (group D) and AIN-93G normal diet group (group E). Indicators were the followings: body weight, food consumption, blood routine, blood biochemical test, organ weight, bone density and pathological examination of organs. At the middle of the experiment, the percentage of monocyte of female group B was less than that of group E (P 0.05), and no notable abnormity in the pathological examination of main organs (P > 0.05). There were no enough evidence to confirm the sub-chronic toxicity of genetically modified rice on rats.

White Thrombus Formation in Blood Tubing Lines in a Chronic Hemodialysis Unit

OpenAIRE

Watnick, Suzanne; Stooksbury, Michael; Winter, Rolf; Riscoe, Michael; Cohen, David M.

2008-01-01

Background and objectives: Previous reports have described white particulate matter in banked blood components, but no prior public reports describe such matter in blood tubing during the course of routine in-center hemodialysis. This report describes the events, investigations, and preliminary conclusions associated with the spontaneous formation of adherent white thrombus in the venous and arterial blood lines during routine in-center hemodialysis treatments.

White blood cell subtypes and risk of type 2 diabetes.

Science.gov (United States)

Zhang, Hongmei; Yang, Zhen; Zhang, Weiwei; Niu, Yixin; Li, Xiaoyong; Qin, Li; Su, Qing

2017-01-01

It is reported that total white blood cell is associated with risk of diabetes mellitus. The present study is to investigate the relationship of white blood cell subsets with incidence of type 2 diabetes at baseline and 3year follow-up. We chose individuals without diabetes history as our study population; 8991 individuals were included at baseline. All of the participants underwent a 75-g OGTT at baseline. White blood cell count including all the subsets were measured along with all the other laboratory indices. The participants who were not diagnosed with type 2 diabetes according to the WHO 1999 diagnostic criteria underwent another 75-g OGTT at 3year follow-up. The total WBC count, neutrophil count, and lymphocyte count were significantly increased in subjects newly diagnosed with diabetes mellitus compared to non-DM subjects at baseline (all ptype 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Micro-fluidic module for blood cell separation for gene expression radiobiological assays

International Nuclear Information System (INIS)

Brengues, Muriel; Gu, Jian; Zenhausern, Frederic

2015-01-01

Advances in molecular techniques have improved discovery of biomarkers associated with radiation exposure. Gene expression techniques have been demonstrated as effective tools for biodosimetry, and different assay platforms with different chemistries are now available. One of the main challenges is to integrate the sample preparation processing of these assays into micro-fluidic platforms to be fully automated for point-of-care medical countermeasures in the case of a radiological event. Most of these assays follow the same workflow processing that comprises first the collection of blood samples followed by cellular and molecular sample preparation. The sample preparation is based on the specific reagents of the assay system and depends also on the different subsets of cells population and the type of biomarkers of interest. In this article, the authors present a module for isolation of white blood cells from peripheral blood as a prerequisite for automation of gene expression assays on a micro-fluidic cartridge. For each sample condition, the gene expression platform can be adapted to suit the requirements of the selected assay chemistry (authors)

Detection of growth hormone doping by gene expression profiling of peripheral blood.

Science.gov (United States)

Mitchell, Christopher J; Nelson, Anne E; Cowley, Mark J; Kaplan, Warren; Stone, Glenn; Sutton, Selina K; Lau, Amie; Lee, Carol M Y; Ho, Ken K Y

2009-12-01

GH abuse is a significant problem in many sports, and there is currently no robust test that allows detection of doping beyond a short window after administration. Our objective was to evaluate gene expression profiling in peripheral blood leukocytes in-vivo as a test for GH doping in humans. Seven men and thirteen women were administered GH, 2 mg/d sc for 8 wk. Blood was collected at baseline and at 8 wk. RNA was extracted from the white cell fraction. Microarray analysis was undertaken using Agilent 44K G4112F arrays using a two-color design. Quantitative RT-PCR using TaqMan gene expression assays was performed for validation of selected differentially expressed genes. GH induced an approximately 2-fold increase in circulating IGF-I that was maintained throughout the 8 wk of the study. GH induced significant changes in gene expression with 353 in women and 41 in men detected with a false discovery rate of less than 5%. None of the differentially expressed genes were common between men and women. The maximal changes were a doubling for up-regulated or halving for down-regulated genes, similar in magnitude to the variation between individuals. Quantitative RT-PCR for seven target genes showed good concordance between microarray and quantitative PCR data in women but not in men. Gene expression analysis of peripheral blood leukocytes is unlikely to be a viable approach for the detection of GH doping.

Development and testing of a new disposable sterile device for labelling white blood cells

NARCIS (Netherlands)

Signore, A.; Glaudemans, A. W. J. M.; Malviya, G.; Lazzeri, E.; Prandini, N.; Viglietti, A. L.; De Vries, E. F. J.; Dierckx, R. A. J. O.

Aim. White blood cell (WBC) labelling requires isolation of cells from patient's blood under sterile conditions using sterile materials, buffers and disposables under good manufacturing practice (GMP) conditions. Till now, this limited the use of white blood cell scintigraphy (WBC-S) only to well

White cell labeling: 20 ML VS 4 ML of blood volume-case reports

International Nuclear Information System (INIS)

Imam, S.K.

1998-01-01

Full text: Some times, it becomes difficult to draw 20 mL blood from a patient with bad veins. On two occasions, we could collect only about 4 mL of blood, that too with a great deal of struggle, and then we carried out the routine labelling procedure. A labelling efficiency of 98.2% and 95.6% was achieved. The white cell scan was negative in one patient, but positive in the next one. In a third patient, a comparison of labelling efficiency was done between 5 and 20 mLs of blood volumes separately and the results were found to be identical, 98.5% and 98.4%, respectively. As we have achieved the usual pattern of white cell scan with as low as 4-5 mL of blood, it appears that enough number of white cells is present even in the 4-5 mL of blood that is capable of generating a white cell scan and so, it seems rational to reduce the blood volume from 20 mL to 4 or 5 mL. However, further studies are warranted before adopting this modification. The procedure appears to carry the following advantages: ease of blood collection, handling and re-injection and less risk to the patient

Hydrogenated fat intake during pregnancy and lactation modifies serum lipid profile and adipokine mRNA in 21-day-old rats.

Science.gov (United States)

Pisani, Luciana P; Oyama, Lila M; Bueno, Allain A; Biz, Carolina; Albuquerque, Kelse T; Ribeiro, Eliane B; Oller do Nascimento, Claudia M

2008-03-01

We examined whether feeding pregnant and lactating rats hydrogenated fats rich in trans-fatty acids modifies the plasma lipid profiles and the expression of adipokines involved with insulin resistance and cardiovascular disease in their 21-d-old offspring. Pregnant and lactating Wistar rats were fed with a control diet (C group) or one enriched with hydrogenated vegetable fat (T group). After delivery, male offspring were weighed weekly and killed at day 21 of life by decapitation. Blood and retroperitoneal, epididymal, and subcutaneous white adipose tissues were collected. Offspring of T-group rats had increased serum triacylglycerols and cholesterol, white adipose tissue plasminogen activator inhibitor-1, and tumor necrosis factor-alpha gene expression, and carcass lipid content and decreased blood leptin and adiponectin and adiponectin gene expression. Ingestion of hydrogenated vegetable fat by the mother during gestation and lactation alters the blood lipid profiles and the expression of proinflammatory adipokynes by the adipose tissue of offspring aged 21 d.

Colour measurement and white blood cell recognition

CERN Document Server

Gelsema, E S

1972-01-01

As a part of a collaboration with NEMCH aimed at the automation of the differential white blood cell count, studies have been made of the different possibilities for using colour to help in the recognition process. Results are presented comparing data obtained with a microspectrophotometer and with a simulated three-colour scanner.

Image resizing using saliency strength map and seam carving for white blood cell analysis

Directory of Open Access Journals (Sweden)

Nam JaeYeal

2010-09-01

Full Text Available Abstract Background A new image-resizing method using seam carving and a Saliency Strength Map (SSM is proposed to preserve important contents, such as white blood cells included in blood cell images. Methods To apply seam carving to cell images, a SSM is initially generated using a visual attention model and the structural properties of white blood cells are then used to create an energy map for seam carving. As a result, the energy map maximizes the energies of the white blood cells, while minimizing the energies of the red blood cells and background. Thus, the use of a SSM allows the proposed method to reduce the image size efficiently, while preserving the important white blood cells. Results Experimental results using the PSNR (Peak Signal-to-Noise Ratio and ROD (Ratio of Distortion of blood cell images confirm that the proposed method is able to produce better resizing results than conventional methods, as the seam carving is performed based on an SSM and energy map. Conclusions For further improvement, a faster medical image resizing method is currently being investigated to reduce the computation time, while maintaining the same image quality.

Image resizing using saliency strength map and seam carving for white blood cell analysis.

Science.gov (United States)

Ko, ByoungChul; Kim, SeongHoon; Nam, JaeYeal

2010-09-20

A new image-resizing method using seam carving and a Saliency Strength Map (SSM) is proposed to preserve important contents, such as white blood cells included in blood cell images. To apply seam carving to cell images, a SSM is initially generated using a visual attention model and the structural properties of white blood cells are then used to create an energy map for seam carving. As a result, the energy map maximizes the energies of the white blood cells, while minimizing the energies of the red blood cells and background. Thus, the use of a SSM allows the proposed method to reduce the image size efficiently, while preserving the important white blood cells. Experimental results using the PSNR (Peak Signal-to-Noise Ratio) and ROD (Ratio of Distortion) of blood cell images confirm that the proposed method is able to produce better resizing results than conventional methods, as the seam carving is performed based on an SSM and energy map. For further improvement, a faster medical image resizing method is currently being investigated to reduce the computation time, while maintaining the same image quality.

Construction and identification of differential expression genes of peripheral blood cells in radon-exposed mice

International Nuclear Information System (INIS)

Chen Rui; Shi Minhua; Hu Huacheng; Li Jianxiang; Nie Jihua; Tong Jian

2009-01-01

Objective: To screen and identify the differential expression genes on peripheral blood cells of mice based on the experimental animal model of radon exposure. Methods: BALB/c mice were exposed in a type HD-3 multifunctional radon-room, with the accumulative doses of radon-exposure group at 105 WLM and control group at 1 WLM. Total RNA was extracted from peripheral blood cells and the methods of SMART for dscDNA synthesis and SSH for gene screening was applied. With the construction of the cDNA library enriched with differentially expressed genes, the pMD 18-T plasmid containing LacZ operator at the multiple cloning site was used to allow a blue-white screening. The TA clones were amplified by nested PCR and the reverse Northern blot was used to identify up and down regulation of the clones. The differently expressed cDNA was then sequenced and analyzed. Results: The subtracted cDNA libraries were successfully constructed. A total of 390 recombinant white colonies were randomly selected. Among the 312 cDNA monoclones selected from both forward- and reverse-subtracted libraries, 41 clones were chosen to sequence for their differential expressions based on reverse Northern blot. Among the 41 sequenced clones, 10 clones with known function/annotation and 3 new ESTs with the GenBank accession numbers were obtained. Most of the known function/annotation genes were revealed to be related with cell proliferation, metabolism, cellular apoptosis and carcinogenesis. Conclusions: The animal model of radon exposure was established and the cDNA library of peripheral blood cells was successfully constructed. Radon exposure could up- and down-regulate a series of genes. Differentially expressed genes could be identified by using SSH technique and the results may help exploring mechanisms of random exposure. (authors)

Fixation of radioactive cerium-144 on white blood cells. Possibilities for use in physiopathology

International Nuclear Information System (INIS)

Aeberhardt, A.

1958-01-01

From the study of the means of transport of cerium in the blood of various laboratory animals, after intra-venous injection of 144 Ce- 144 Pr without carrier, we have been able to show up the part played by the white cells in the transport of this fission product during its passage in the blood. This observation has led to the study, in vitro, of the methods of cerium fixation on the white cells, with a view to determining the possibilities of using this property for white cell labelling, the methods used up to the present not being entirely satisfactory. Using the method for the separation of the known constituents of the blood proposed by us in 1956, we have studied the cerium fixation under various conditions: - on suspensions of white cells from the rabbit, - on a suspension of human white cells, - on the white cells in whole from the rabbit. (author) [fr

Transcriptome analysis of the white body of the squid Euprymna tasmanica with emphasis on immune and hematopoietic gene discovery.

Directory of Open Access Journals (Sweden)

Karla A Salazar

Full Text Available In the mutualistic relationship between the squid Euprymna tasmanica and the bioluminescent bacterium Vibrio fischeri, several host factors, including immune-related proteins, are known to interact and respond specifically and exclusively to the presence of the symbiont. In squid and octopus, the white body is considered to be an immune organ mainly due to the fact that blood cells, or hemocytes, are known to be present in high numbers and in different developmental stages. Hence, the white body has been described as the site of hematopoiesis in cephalopods. However, to our knowledge, there are no studies showing any molecular evidence of such functions. In this study, we performed a transcriptomic analysis of white body tissue of the Southern dumpling squid, E. tasmanica. Our primary goal was to gain insights into the functions of this tissue and to test for the presence of gene transcripts associated with hematopoietic and immune processes. Several hematopoiesis genes including CPSF1, GATA 2, TFIID, and FGFR2 were found to be expressed in the white body. In addition, transcripts associated with immune-related signal transduction pathways, such as the toll-like receptor/NF-κβ, and MAPK pathways were also found, as well as other immune genes previously identified in E. tasmanica's sister species, E. scolopes. This study is the first to analyze an immune organ within cephalopods, and to provide gene expression data supporting the white body as a hematopoietic tissue.

White thrombus formation in blood tubing lines in a chronic hemodialysis unit.

Science.gov (United States)

Watnick, Suzanne; Stooksbury, Michael; Winter, Rolf; Riscoe, Michael; Cohen, David M

2008-03-01

Previous reports have described white particulate matter in banked blood components, but no prior public reports describe such matter in blood tubing during the course of routine in-center hemodialysis. This report describes the events, investigations, and preliminary conclusions associated with the spontaneous formation of adherent white thrombus in the venous and arterial blood lines during routine in-center hemodialysis treatments. Design setting, participants, & measurements: This investigation occurred at the Portland Veterans Administration Medical Center (PVAMC) Hemodialysis Unit from October 2006 through April 2007. Sixty-eight variables regarding demographics, medical history and dialysis treatments were collected on our 34 chronic hemodialysis outpatients. Over a 5-wk interval, 62% (21 of 34) of the chronic hemodialysis patients unexpectedly developed a white precipitate adhering to the lumenal surface of their dialysis blood tubing, with 73 of 580 chronic dialysis treatments exhibiting the phenomenon. Microscopic and biochemical analyses were consistent with white thrombus, formed by an aggregation of platelets and fibrin. An alert was issued and other in-center hemodialysis units noted similar findings. This was remedied by the removal of specific tubing. Both patient-specific and tubing-specific factors may have been operative. Although patient safety was not adversely affected, assessment of clinical and manufacturing variables potentially affecting platelet activation is warranted.

Effect of emulsifiers on complexation and retrogradation characteristics of native and chemically modified White sorghum (Sorghum bicolor) starch

International Nuclear Information System (INIS)

Ali, Tahira Mohsin; Hasnain, Abid

2013-01-01

Highlights: ► Sorghum starches were chemically modified. ► Starch–lipid complexes were studied in the presence of emulsifiers. ► Type II complexes were also detected in native and oxidized starches on adding GMS. ► Starch–lipid complexes sharply reduced retrogradation in modified starches. - Abstract: The effect of emulsifiers on complexation and retrogradation characteristics of native and chemically modified white sorghum starches was studied. Complex forming tendency of white sorghum starch with commercially available emulsifiers GMS and DATEM improved after acetylation. Presence of emulsifiers reduced λ max (wavelength of maximum absorbance) both for native and modified sorghum starches suggesting lower availability of amylose chains to complex with iodine. In native white sorghum starch (NWSS) and oxidized white sorghum starch (OWSS), both Type I and Type II starch–lipid complexes were observed on addition of 1.0% GMS prior to gelatinization. Acetylated-oxidized white sorghum starch (AOWSS) formed weakest complexes among all the modified starches. The results revealed that antistaling characteristics of modified sorghum starches were enhanced when used in combination with emulsifiers. The most prominent decline in reassociative capability among modified starches was observed for acetylated starches.

In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis.

Directory of Open Access Journals (Sweden)

Pascal Trouvé

Full Text Available Cystic Fibrosis is the most common lethal autosomal recessive disorder in the white population, affecting among other organs, the lung, the pancreas and the liver. Whereas Cystic Fibrosis is a monogenic disease, many studies reveal a very complex relationship between genotype and clinical phenotype. Indeed, the broad phenotypic spectrum observed in Cystic Fibrosis is far from being explained by obvious genotype-phenotype correlations and it is admitted that Cystic Fibrosis disease is the result of multiple factors, including effects of the environment as well as modifier genes. Our objective was to highlight new modifier genes with potential implications in the lung, pancreatic and liver outcomes of the disease. For this purpose we performed a system biology approach which combined, database mining, literature mining, gene expression study and network analysis as well as pathway enrichment analysis and protein-protein interactions. We found that IFI16, CCNE2 and IGFBP2 are potential modifiers in the altered lung function in Cystic Fibrosis. We also found that EPHX1, HLA-DQA1, HLA-DQB1, DSP and SLC33A1, GPNMB, NCF2, RASGRP1, LGALS3 and PTPN13, are potential modifiers in pancreas and liver, respectively. Associated pathways indicate that immune system is likely involved and that Ubiquitin C is probably a central node, linking Cystic Fibrosis to liver and pancreatic disease. We highlight here new modifier genes with potential implications in Cystic Fibrosis. Nevertheless, our in silico analysis requires functional analysis to give our results a physiological relevance.

White blood cell counting analysis of blood smear images using various segmentation strategies

Science.gov (United States)

Safuan, Syadia Nabilah Mohd; Tomari, Razali; Zakaria, Wan Nurshazwani Wan; Othman, Nurmiza

2017-09-01

In white blood cell (WBC) diagnosis, the most crucial measurement parameter is the WBC counting. Such information is widely used to evaluate the effectiveness of cancer therapy and to diagnose several hidden infection within human body. The current practice of manual WBC counting is laborious and a very subjective assessment which leads to the invention of computer aided system (CAS) with rigorous image processing solution. In the CAS counting work, segmentation is the crucial step to ensure the accuracy of the counted cell. The optimal segmentation strategy that can work under various blood smeared image acquisition conditions is remain a great challenge. In this paper, a comparison between different segmentation methods based on color space analysis to get the best counting outcome is elaborated. Initially, color space correction is applied to the original blood smeared image to standardize the image color intensity level. Next, white blood cell segmentation is performed by using combination of several color analysis subtraction which are RGB, CMYK and HSV, and Otsu thresholding. Noises and unwanted regions that present after the segmentation process is eliminated by applying a combination of morphological and Connected Component Labelling (CCL) filter. Eventually, Circle Hough Transform (CHT) method is applied to the segmented image to estimate the number of WBC including the one under the clump region. From the experiment, it is found that G-S yields the best performance.

Sorting of White Blood Cells in a Lattice

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Carlson, Robert; Chan, Shirley; Gabel, Chris; Austin, Robert

1997-03-01

White blood cells represent a heterogenous population of differentially sticky and deformable objects. We examine here experiemnts where the hydrodynamic flow of such a population in a lattice of obstacles results in the fractionation of the objects, and will present modeling of the observed fractionation of the objects.

SNP-by-fitness and SNP-by-BMI interactions from seven candidate genes and incident hypertension after 20 years of follow-up: the CARDIA Fitness Study.

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Sarzynski, M A; Rankinen, T; Sternfeld, B; Fornage, M; Sidney, S; Bouchard, C

2011-08-01

The association of single nucleotide polymorphisms (SNPs) from seven candidate genes, including genotype-by-baseline fitness and genotype-by-baseline body mass index (BMI) interactions, with incident hypertension over 20 years was investigated in 2663 participants (1301 blacks, 1362 whites) of the Coronary Artery Risk Development in Young Adults Study (CARDIA). Baseline cardiorespiratory fitness was determined from duration of a modified Balke treadmill test. A total of 98 SNPs in blacks and 89 SNPs in whites from seven candidate genes were genotyped. Participants that became hypertensive (295 blacks and 146 whites) had significantly higher blood pressure and BMI (both races), and lower fitness (blacks only) at baseline than those who remained normotensive. Markers at the peroxisome proliferative activated receptor gamma coactivator 1α (PPARGC1A) and bradykinin β2 receptor (BDKRB2) genes were nominally associated with greater risk of hypertension, although one marker each at the BDKRB2 and endothelial nitric oxide synthase-3 (NOS3) genes were nominally associated with lower risk. The association of baseline fitness with risk of hypertension was nominally modified by genotype at markers within the angiotensin converting enzyme, angiotensinogen, BDKRB2 and NOS3 genes in blacks and the BDKRB2, endothelin-1 and PPARGC1A genes in whites. BDKRB2 rs4900318 showed nominal interactions with baseline fitness on the risk of hypertension in both races. The association of baseline BMI with risk of hypertension was nominally modified by GNB3 rs2301339 genotype in whites. None of the above associations were statistically significant after correcting for multiple testing. We found that SNPs in these candidate genes did not modify the association between baseline fitness or BMI and risk of hypertension in CARDIA participants.

Modified Beer-Lambert law for blood flow.

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Baker, Wesley B; Parthasarathy, Ashwin B; Busch, David R; Mesquita, Rickson C; Greenberg, Joel H; Yodh, A G

2014-11-01

We develop and validate a Modified Beer-Lambert law for blood flow based on diffuse correlation spectroscopy (DCS) measurements. The new formulation enables blood flow monitoring from temporal intensity autocorrelation function data taken at single or multiple delay-times. Consequentially, the speed of the optical blood flow measurement can be substantially increased. The scheme facilitates blood flow monitoring of highly scattering tissues in geometries wherein light propagation is diffusive or non-diffusive, and it is particularly well-suited for utilization with pressure measurement paradigms that employ differential flow signals to reduce contributions of superficial tissues.

Exercise induced upregulation of glutamate-cysteine ligase catalytic subunit and glutamate-cysteine ligase modifier subunit gene expression in Thoroughbred horses

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Jeong-Woong Park

2017-05-01

Full Text Available Objective This study was performed to reveal the molecular structure and expression patterns of horse glutamate-cysteine ligase catalytic subunit (GCLC and glutamate-cysteine ligase modifier subunit (GCLM genes whose products form glutamate cysteine ligase, which were identified as differentially expressed genes in the previous study. Methods We performed bioinformatics analyses, and gene expression assay with quantitative polymerase chain reaction (qPCR for horse GCLC and GCLM genes in muscle and blood leukocytes of Thoroughbred horses Results Expression of GCLC showed the same pattern in both blood and muscle tissues after exercise. Expression of GCLC increased in the muscle and blood of Thoroughbreds, suggesting a tissue-specific regulatory mechanism for the expression of GCLC. In addition, expression of the GCLM gene increased after exercise in both the blood and muscle of Thoroughbreds. Conclusion We established the expression patterns of GCLC and GCLM in the skeletal muscle and blood of Thoroughbred horses in response to exercise. Further study is now warranted to uncover the functional importance of these genes in exercise and recovery in racehorses.

Novel Cell Preservation Technique to Extend Bovine In Vitro White Blood Cell Viability.

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Emilie L Laurin

Full Text Available Although cell-mediated immunity based diagnostics can be integral assays for early detection of various diseases of dairy cows, processing of blood samples for these tests is time-sensitive, often within 24 hours of collection, to maintain white blood cell viability. Therefore, to improve utility and practicality of such assays, the objective of this study was to assess the use of a novel white blood cell preservation technology in whole bovine blood. Blood samples from ten healthy cows were each divided into an unpreserved control sample and a test sample preserved with commercially-available cell transport medium. Samples were maintained at room temperature and stimulated with the mitogens pokeweed and concanavalinA, as well as with interleukin-12 p40. Stimulation was completed on days 1, 5, and 8 post-sampling. Viability of white blood cells was assessed through interferon gamma production determined with a commercial enzyme linked immunosorbent assay. In addition, mononuclear cell viability was assessed with propidium iodide flow cytometry. Greater interferon gamma production was observed on days 5 and 8 post-collection in preserved samples, with both pokeweed and concanavalinA stimulating positive interferon gamma production on day 5 post-collection. A greater proportion of the amount of interferon gamma produced on day 1 continued to be produced on days 5 and 8 post-collection with concanavalinA stimulation (with or without interleukin 12 as compared to pokeweed stimulation. Additionally, viable mononuclear cells were still present at eight days post-collection, with a higher mean proportion detected at days 5 and 8 in all stimulated preserved samples. This practical and simple method to extend in vitro white blood cell viability could benefit the efficient utilization of cell-based blood tests in ruminants.

The Utility of Ambulatory Blood Pressure Monitoring for Diagnosing White Coat Hypertension in Older Adults.

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Reynolds, Kristi; Bowling, C Barrett; Sim, John J; Sridharan, Lakshmi; Harrison, Teresa N; Shimbo, Daichi

2015-11-01

The beneficial effect of antihypertensive medication on reducing the risk of cardiovascular disease (CVD) events is supported by data from randomized controlled trials of older adults with hypertension. However, in clinical practice, overtreatment of hypertension in older adults may lead to side effects and an increased risk of falls. The diagnosis and treatment of hypertension is primarily based on blood pressure measurements obtained in the clinic setting. Ambulatory blood pressure monitoring (ABPM) complements clinic blood pressure by measuring blood pressure in the out-of-clinic setting. ABPM can be used to identify white coat hypertension, defined as elevated clinic blood pressure and non-elevated ambulatory blood pressure. White coat hypertension is common in older adults but does not appear to be associated with an increased risk of CVD events among this population. Herein, we review the current literature on ABPM in the diagnoses of white coat hypertension in older adults, including its potential role in preventing overtreatment.

The Utility of Ambulatory Blood Pressure Monitoring for Diagnosing White Coat Hypertension in Older Adults

Science.gov (United States)

Reynolds, Kristi; Bowling, C. Barrett; Sim, John J.; Sridharan, Lakshmi; Harrison, Teresa N.; Shimbo, Daichi

2015-01-01

The beneficial effect of antihypertensive medication on reducing the risk of cardiovascular disease (CVD) events is supported by data from randomized controlled trials of older adults with hypertension. However, in clinical practice, overtreatment of hypertension in older adults may lead to side effects and an increased risk of falls. The diagnosis and treatment of hypertension is primarily based on blood pressure measurements obtained in the clinic setting. Ambulatory blood pressure monitoring (ABPM) complements clinic blood pressure by measuring blood pressure in the out-of-clinic setting. ABPM can be used to identify white coat hypertension, defined as elevated clinic blood pressure and non-elevated ambulatory blood pressure. White coat hypertension is common in older adults but does not appear to be associated with an increased risk of CVD events among this population. Herein, we review the current literature on ABPM in the diagnoses of white coat hypertension in older adults, including its potential role in preventing overtreatment. PMID:26400076

Study on the peripheral white blood cell count in patients with type 2 diabetes complicated with microangiopathy

International Nuclear Information System (INIS)

Cai Wenpin; Zhu Pinghui

2010-01-01

Objective: To study the possible role played by peripheral white blood cells in the development of type 2 diabetes (DM2) and complication of microvascular pathological changes. Methods: White blood cell count and metabolism related parameters (FBG, 2hPBG, 2h Pinsulin, TCH, HDL, LDL, TG, HbA1c, BMI, age) were examined in 33 DM2 patients without complication, 41 DM2 patients with micro-angiopathy and 31 controls. Results: The white blood cell counts in both DM2 patients with no complication and the DM2 with microvascular pathological changes were significantly higher than those in controls (P 0.05). The white blood cell counts were positively correlated with age,body metabolism index (BMI), triglyceride (TG), 2h glucose (PBG) and 2h insulin (the r value 0.248, 0.201, 0.435, 0.225, 0.352 respectively, P<0.05). Conclusion: Peripheral white blood cells possibly played some role in development of DM2 and microvascular pathological changes and might be of some predictive importance. (authors)

Automatic white blood cell classification using pre-trained deep learning models: ResNet and Inception

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Habibzadeh, Mehdi; Jannesari, Mahboobeh; Rezaei, Zahra; Baharvand, Hossein; Totonchi, Mehdi

2018-04-01

This works gives an account of evaluation of white blood cell differential counts via computer aided diagnosis (CAD) system and hematology rules. Leukocytes, also called white blood cells (WBCs) play main role of the immune system. Leukocyte is responsible for phagocytosis and immunity and therefore in defense against infection involving the fatal diseases incidence and mortality related issues. Admittedly, microscopic examination of blood samples is a time consuming, expensive and error-prone task. A manual diagnosis would search for specific Leukocytes and number abnormalities in the blood slides while complete blood count (CBC) examination is performed. Complications may arise from the large number of varying samples including different types of Leukocytes, related sub-types and concentration in blood, which makes the analysis prone to human error. This process can be automated by computerized techniques which are more reliable and economical. In essence, we seek to determine a fast, accurate mechanism for classification and gather information about distribution of white blood evidences which may help to diagnose the degree of any abnormalities during CBC test. In this work, we consider the problem of pre-processing and supervised classification of white blood cells into their four primary types including Neutrophils, Eosinophils, Lymphocytes, and Monocytes using a consecutive proposed deep learning framework. For first step, this research proposes three consecutive pre-processing calculations namely are color distortion; bounding box distortion (crop) and image flipping mirroring. In second phase, white blood cell recognition performed with hierarchy topological feature extraction using Inception and ResNet architectures. Finally, the results obtained from the preliminary analysis of cell classification with (11200) training samples and 1244 white blood cells evaluation data set are presented in confusion matrices and interpreted using accuracy rate, and false

Assessment of hand blood flow: a modified technique

International Nuclear Information System (INIS)

Kirsh, J.C.; Tepperman, P.S.

1985-01-01

A blood flow artifact has been identified with the conventional bolus-injection technique in radionuclide studies of hand disorders. The artifact, consisting of increased blood flow on the injected side, was demonstrated in 22 of 25 subjects. Using a modified injection technique to allow time for local blood flow to return to the basal state, the artifact could be eliminated in 19 of 23 additional subjects. Use of this simple protocol should help avoid misinterpretation of blood flow asymmetry in the assessment of hand disorders

Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations.

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Gorlova, Olga Y; Li, Yafang; Gorlov, Ivan; Ying, Jun; Chen, Wei V; Assassi, Shervin; Reveille, John D; Arnett, Frank C; Zhou, Xiaodong; Bossini-Castillo, Lara; Lopez-Isac, Elena; Acosta-Herrera, Marialbert; Gregersen, Peter K; Lee, Annette T; Steen, Virginia D; Fessler, Barri J; Khanna, Dinesh; Schiopu, Elena; Silver, Richard M; Molitor, Jerry A; Furst, Daniel E; Kafaja, Suzanne; Simms, Robert W; Lafyatis, Robert A; Carreira, Patricia; Simeon, Carmen Pilar; Castellvi, Ivan; Beltran, Emma; Ortego, Norberto; Amos, Christopher I; Martin, Javier; Mayes, Maureen D

2018-01-01

Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations were shared in African-American and White populations, using data from ImmunoChip and GWAS genotyping studies. The White sample included 1833 cases and 3466 controls (956 cases and 2741 controls from the US and 877 cases and 725 controls from Spain) and the African American sample, 291 cases and 260 controls. In both Whites and African Americans, we performed a gene-level analysis that integrates association statistics in a gene possibly harboring multiple SNPs with weak effect on disease risk, using Versatile Gene-based Association Study (VEGAS) software. The SNP-level analysis was performed using PLINK v.1.07. We identified 4 novel candidate genes (STAT1, FCGR2C, NIPSNAP3B, and SCT) significantly associated and 4 genes (SERBP1, PINX1, TMEM175 and EXOC2) suggestively associated with SSc in the gene level analysis in White patients. As an exploratory analysis we compared the results on Whites with those from African Americans. Of previously established susceptibility genes identified in Whites, only TNFAIP3 was significant at the nominal level (p = 6.13x10-3) in African Americans in the gene-level analysis of the ImmunoChip data. Among the top suggestive novel genes identified in Whites based on the ImmunoChip data, FCGR2C and PINX1 were only nominally significant in African Americans (p = 0.016 and p = 0.028, respectively), while among the top novel genes identified in the gene-level analysis in African Americans, UNC5C (p = 5.57x10-4) and CLEC16A (p = 0.0463) were also nominally significant in Whites. We also present the gene-level analysis of SSc clinical and autoantibody phenotypes among Whites. Our findings need to be validated by independent studies, particularly

Red flag on the white reporter: a versatile insulator abuts the white gene in Drosophila and is omnipresent in mini-white constructs.

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Chetverina, Darya; Savitskaya, Ekaterina; Maksimenko, Oksana; Melnikova, Larisa; Zaytseva, Olga; Parshikov, Alexander; Galkin, Alexander V; Georgiev, Pavel

2008-02-01

Much of the research on insulators in Drosophila has been done with transgenic constructs using the white gene (mini-white) as reporter. Hereby we report that the sequence between the white and CG32795 genes in Drosophila melanogaster contains an insulator of a novel kind. Its functional core is within a 368 bp segment almost contiguous to the white 3'UTR, hence we name it as Wari (white-abutting resident insulator). Though Wari contains no binding sites for known insulator proteins and does not require Su(Hw) or Mod(mdg4) for its activity, it can equally well interact with another copy of Wari and with unrelated Su(Hw)-dependent insulators, gypsy or 1A2. In its natural downstream position, Wari reinforces enhancer blocking by any of the three insulators placed between the enhancer and the promoter; again, Wari-Wari, Wari-gypsy or 1A2-Wari pairing results in mutual neutralization (insulator bypass) when they precede the promoter. The distressing issue is that this element hides in all mini-white constructs employed worldwide to study various insulators and other regulatory elements as well as long-range genomic interactions, and its versatile effects could have seriously influenced the results and conclusions of many works.

Effect of Gamma Irradiation on Polymer Modified White Sand Cement Mortar Composites

International Nuclear Information System (INIS)

Khattab, M.M.

2012-01-01

This study focuses on the substitution effect of standard sand of conventional cement mortar made from ordinary Portland cement (OPC) and standard sand (SS) OPC/SS 1:3; by different ratios of white sand (WS) powder to prepare three types of white sand cement mortar designated as 1OPC:2SS:1WS, 1OPC:1SS:2WS and 1OPC:0SS:3WS. The prepared samples were first cured under tap water for different time intervals namely 3, 7, 28 and 90 days. The effect of addition of 10% styrene-acrylic ester (SAE) as well as the effect of different doses of gamma rays (10, 20, 30 and 50 kGy) on the physicomechanical properties of polymer modified white sand cement mortar specimens also discussed. Compression strength test, total porosity and water absorption percentages were measured according to standard specifications. The obtained data indicated that, the cement mortar samples containing different ratios of white sand have lower values of compressive strength as compared to the conventional cement mortar while, the percentages of total porosity and water absorption increased. On the other hand, the polymer modified mortar specimens showed a noticeably enhancement in the physico-mechanical properties under the effect of gamma-radiation than those of untreated samples. These results were confirmed by scanning electron microscopy (SEM), and thermogravimetric analysis (TGA) studies

Lower white blood cell counts in elite athletes training for highly aerobic sports.

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Horn, P L; Pyne, D B; Hopkins, W G; Barnes, C J

2010-11-01

White cell counts at rest might be lower in athletes participating in selected endurance-type sports. Here, we analysed blood tests of elite athletes collected over a 10-year period. Reference ranges were established for 14 female and 14 male sports involving 3,679 samples from 937 females and 4,654 samples from 1,310 males. Total white blood cell counts and counts of neutrophils, lymphocytes and monocytes were quantified. Each sport was scaled (1-5) for its perceived metabolic stress (aerobic-anaerobic) and mechanical stress (concentric-eccentric) by 13 sports physiologists. Substantially lower total white cell and neutrophil counts were observed in aerobic sports of cycling and triathlon (~16% of test results below the normal reference range) compared with team or skill-based sports such as water polo, cricket and volleyball. Mechanical stress of sports had less effect on the distribution of cell counts. The lower white cell counts in athletes in aerobic sports probably represent an adaptive response, not underlying pathology.

White Blood Cell Segmentation by Circle Detection Using Electromagnetism-Like Optimization

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Erik Cuevas

2013-01-01

Full Text Available Medical imaging is a relevant field of application of image processing algorithms. In particular, the analysis of white blood cell (WBC images has engaged researchers from fields of medicine and computer vision alike. Since WBCs can be approximated by a quasicircular form, a circular detector algorithm may be successfully applied. This paper presents an algorithm for the automatic detection of white blood cells embedded into complicated and cluttered smear images that considers the complete process as a circle detection problem. The approach is based on a nature-inspired technique called the electromagnetism-like optimization (EMO algorithm which is a heuristic method that follows electromagnetism principles for solving complex optimization problems. The proposed approach uses an objective function which measures the resemblance of a candidate circle to an actual WBC. Guided by the values of such objective function, the set of encoded candidate circles are evolved by using EMO, so that they can fit into the actual blood cells contained in the edge map of the image. Experimental results from blood cell images with a varying range of complexity are included to validate the efficiency of the proposed technique regarding detection, robustness, and stability.

White Blood Cell Segmentation by Circle Detection Using Electromagnetism-Like Optimization

Science.gov (United States)

Oliva, Diego; Díaz, Margarita; Zaldivar, Daniel; Pérez-Cisneros, Marco; Pajares, Gonzalo

2013-01-01

Medical imaging is a relevant field of application of image processing algorithms. In particular, the analysis of white blood cell (WBC) images has engaged researchers from fields of medicine and computer vision alike. Since WBCs can be approximated by a quasicircular form, a circular detector algorithm may be successfully applied. This paper presents an algorithm for the automatic detection of white blood cells embedded into complicated and cluttered smear images that considers the complete process as a circle detection problem. The approach is based on a nature-inspired technique called the electromagnetism-like optimization (EMO) algorithm which is a heuristic method that follows electromagnetism principles for solving complex optimization problems. The proposed approach uses an objective function which measures the resemblance of a candidate circle to an actual WBC. Guided by the values of such objective function, the set of encoded candidate circles are evolved by using EMO, so that they can fit into the actual blood cells contained in the edge map of the image. Experimental results from blood cell images with a varying range of complexity are included to validate the efficiency of the proposed technique regarding detection, robustness, and stability. PMID:23476713

Transcriptomic profiles of peripheral white blood cells in type II diabetes and racial differences in expression profiles

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Mao Jinghe

2011-12-01

Full Text Available Abstract Background Along with obesity, physical inactivity, and family history of metabolic disorders, African American ethnicity is a risk factor for type 2 diabetes (T2D in the United States. However, little is known about the differences in gene expression and transcriptomic profiles of blood in T2D between African Americans (AA and Caucasians (CAU, and microarray analysis of peripheral white blood cells (WBCs from these two ethnic groups will facilitate our understanding of the underlying molecular mechanism in T2D and identify genetic biomarkers responsible for the disparities. Results A whole human genome oligomicroarray of peripheral WBCs was performed on 144 samples obtained from 84 patients with T2D (44 AA and 40 CAU and 60 healthy controls (28 AA and 32 CAU. The results showed that 30 genes had significant difference in expression between patients and controls (a fold change of 1.4 with a P value Conclusions These newly identified genetic markers in WBCs provide valuable information about the pathophysiology of T2D and can be used for diagnosis and pharmaceutical drug design. Our results also found that AA and CAU patients with T2D express genes and pathways differently.

Analysis of Prolactin Gene Exon 4 Diversity in Peking, White Mojosari, and Peking White Mojosari Crossbreed

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M. Indriati

2016-04-01

Full Text Available Genetic marker linked to loci reproductive traits could be used to increase an effectiveness of improvement in animal breeding. Association between DNA polymorphism and a trait could be considered as candidate genetic marker for marker assisted selection (MAS programs. Prolactin (PRL is one of polypeptide hormones secreted by anterior pituitary gland in vertebrates. PRL plays an important role in onset of poultry incubation and brooding behavior. The aim of this study was to investigate the diversity of prolactin gene and to characterize the type of mutation in partial intron 3, intron 4 and exon 4 of duck prolactin gene. Blood extraction was collected from 168 ducks consisted of 19 Peking, 36 Mojosari, and 113 Peking White Mojosari (Peking Mojosari putih ducks. Polymerase chain reaction of fragment prolactin gene exon 4 and partial intron 3 and 4 have been successfully amplified with length of base pair were 496 bp. A total of 30 µL PCR product from each sample were sequenced for forward sequence using BIOTRACE 3730 by First Base Company, Malaysia. Alignment analysis found six SNP consisted of g.3941T>G, g.3975C>A, g.4110T>C, INDEL 3724A, INDEL 34031, and INDEL 3939A. Analysis of SNP frequency result indicated mutation of INDEL 3724A, g.3941T>G, g.3975C>A, INDEL 4031A and g.4110T>A in duck sample were polymorphic and INDEL 3939A were monomorphic.

Diurnal gene expression of lipolytic natriuretic peptide receptors in white adipose tissue

DEFF Research Database (Denmark)

Smith, Julie; Fahrenkrug, Jan; Jørgensen, Henrik L

2015-01-01

Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart, but the tem......Disruption of the circadian rhythm can lead to obesity and cardiovascular disease. In white adipose tissue, activation of the natriuretic peptide receptors (NPRs) stimulates lipolysis. We have previously shown that natriuretic peptides are expressed in a circadian manner in the heart......, but the temporal expression profile of their cognate receptors has not been examined in white adipose tissue. We therefore collected peri-renal white adipose tissue and serum from WT mice. Tissue mRNA contents of NPRs - NPR-A and NPR-C, the clock genes Per1 and Bmal1, and transcripts involved in lipid metabolism...... in serum peaked in the active dark period (P=0.003). In conclusion, NPR-A and NPR-C gene expression is associated with the expression of clock genes in white adipose tissue. The reciprocal expression may thus contribute to regulate lipolysis and energy homeostasis in a diurnal manner....

GRIN2B Gene and Associated Brain Cortical White Matter Changes in Bipolar Disorder: A Preliminary Combined Platform Investigation

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Carissa Nadia Kuswanto

2013-01-01

Full Text Available Abnormalities in glutamate signaling and glutamate toxicity are thought to be important in the pathophysiology of bipolar disorder (BD. Whilst previous studies have found brain white matter changes in BD, there is paucity of data about how glutamatergic genes affect brain white matter integrity in BD. Based on extant neuroimaging data, we hypothesized that GRIN2B risk allele is associated with reductions of brain white matter integrity in the frontal, parietal, temporal, and occipital regions and cingulate gyrus in BD. Fourteen patients with BD and 22 healthy controls matched in terms of age, gender and handedness were genotyped using blood samples and underwent diffusion tensor imaging. Compared to G allele, brain FA values were significantly lower in BD patients with risk T allele in left frontal region (P=0.001, right frontal region (P=0.002, left parietal region (P=0.001, left occipital region (P=0.001, right occipital region (P<0.001, and left cingulate gyrus (P=0.001. Further elucidation of the interactions between different glutamate genes and their relationships with such structural, functional brain substrates will enhance our understanding of the link between dysregulated glutamatergic neurotransmission and neuroimaging endophenotypes in BD.

White blood cell scintigraphy for differentiation of infection and aseptic loosening

DEFF Research Database (Denmark)

Simonsen, Lene; Buhl, Anna; Oersnes, Thue

2007-01-01

Diagnosis of an infected arthroplasty is often difficult. Fever, abnormal physical findings, radiographic changes, findings at bone scintigraphy, an elevated erythrocyte sedimentation rate, CRP, and leucocytosis are not specific enough. We evaluated the diagnostic value of white blood cell...

Enhancement of light absorption by blood to Nd:YAG laser using PEG-modified gold nanorods.

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Xing, Linzhuang; Li, Dong; Chen, Bin; Dai, Yuze; Wu, Wenjuan; Wang, Guoxiang

2016-10-01

On the basis of the principle of selective photothermolysis, laser therapy has been the most effective treatment strategy for Port-wine stains (PWSs) caused by the expansion of dermal capillaries. Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser at 1064 nm wavelength has great potential for deeply buried PWS, although its application is limited because of its weak absorption by blood. The purpose of this study is to investigate the effect of PEG-modified gold nanorods (NRs) on the blood absorption enhancement for Nd:YAG laser. PEG-modified gold nanorods (NRs) were synthesized via the seeded growth method. Then, the effect of PEG-modified gold NRs on blood light absorbance was investigated through adding different concentration of PEG-modified gold NRs to 1 ml of blood at room temperature. Finally, the optical properties of whole mice blood with or without PEG-modified gold NRs under slow heating were investigated. The average length and width of PEG-modified gold NRs are 79.5 ± 10.5 and 13.5 ± 0.9 nm, respectively, with the aspect ratio of 5.89, and a strong absorption peak exists at ∼1050 nm in the near-infrared range. A linear correlation between the blood absorbance at 1064 nm and the amount of PEG-modified gold NRs was obtained. The absorbance at 1064 nm increased 17.6, 33.0, 48.3, and 65.4 times when 0.4, 0.8, 1.2, and 1.6 mg of PEG-modified gold NRs was added to 1 ml of blood at room temperature, respectively. After adding 0.8 mg of PEG-modified gold NRs to 1 ml of blood, blood absorbance at 1064 nm at different temperatures increased by an average of 24.0 times. After intravenously injecting PEG-modified gold NRs (0.87 mg/ml) into Sprague-Dawley mice, the blood absorbance at 1064 nm increased from 0.014 to 0.5. Our findings suggest that PEG-modified gold NRs injection is an efficient way to enhance light absorption by blood to Nd:YAG laser. Lasers Surg. Med. 48:790-803, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley

Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI

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Cramer, Stig Præstekær; Simonsen, Helle Juhl; Frederiksen, Jette Lautrup Battistini

2013-01-01

To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics.......To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics....

Ocular Blood Flow Measurements in Healthy White Subjects Using Laser Speckle Flowgraphy.

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Nikolaus Luft

Full Text Available To assess the feasibility and reliability of Laser Speckle Flowgraphy (LSFG to measure ocular perfusion in a sample of healthy white subjects and to elucidate the age-dependence of the parameters obtained.This cross-sectional study included 80 eyes of 80 healthy, non-smoking white subjects of Western European descent between 19 and 79 years of age. A commercial LSFG instrument was applied to measure ocular blood flow at the optic nerve head (ONH three successive times before and after pharmacological pupil dilation. The mean blur rate (MBR, a measure of relative blood flow velocity, was obtained for different regions of the ONH. Eight parameters of ocular perfusion derived from the pulse-waveform analysis of MBR including blowout time (BOT and falling rate (FR were also recorded.Artifact-free LSFG images meeting the quality criteria for automated image analysis were obtainable in 93.8% without pupil dilation and in 98.8% with pharmacological pupil dilation. Measurements of MBR showed excellent repeatability with intraclass correlation coefficients ≥ 0.937 and were barely affected by pupil dilation. The majority of pulse-waveform derived variables exhibited equally high repeatability. MBR-related blood flow indices exhibited significant age dependence (p<0.001. FR (r = 0.747, p<0.001 and BOT (r = -0.714, p<0.001 most strongly correlated with age.LSFG represents a reliable method for the quantitative assessment of ocular blood flow in white subjects. Our data affirms that the LSFG-derived variables FR and BOT may be useful biomarkers for age-related changes in ocular perfusion.

DNA Damages and White Blood Cell Death Processes in Victims with Severe Injury

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V. V. Moroz

2014-01-01

Full Text Available Objective. To study the mechanisms of posttraumatic changes in the blood cells, by investigating DNA damages associat ed with hypoxia caused by massive blood loss (BL in severe injury.Subjects and methods. Ninetyfive patients aged 40.6±16.5 years (from 20 to 79 years who had sustained severe mechanical injury with different BL volumes (BLV (from 100 to 4000 ml and hemodynamic disorders were examined to study DNA damages and white blood cell necrotic and apop totic processes. In terms of the victims' weight, the mean BL was 21.5±16.5 ml/kg (from 1.4 to 61.5 ml/kg. The victimswere divided into 4 groups according to BLV: 1 26 victims whose BLV was less than 750 ml (5.93±2.41 ml/kg (grade I BL; 2 23 victims whose BLV was 750—1500 ml (11.5±1.5 ml/kg (grade 2 BL; 3 23 victims whose BLV was 1500—2000 ml (23.8±4.0 ml/kg (grade 3 BL; 4 23 victims whose BLV was over 2000 ml (45.6±10.1 ml/kg (grade 4 BL, according to the type of injury: 1 severe skeletal injury (SSI (n=17; 2 brain injury (BI (n=43; 3 a concurrence of SSI and BI (SSI+BI (n=35; according to the development of infectious complications: 1 69 victims who developed infectious com plications on days 5—7 postinjury; 2 26 victims who did not. To evaluate the impact of hypoxia on DNA damages, white blood cell apoptotic and necrotic processes, the victims were divided into 2 groups: 1 hypoxia (18 of the 95 victims who had 4 altered indicators, such as capillary blood pO2, plasma lactate levels, pH, and BE; 2 no hypoxia (10 of the 95 victims whose indicators were within the normal range. DNA damages and necrotic and apoptotic changes in the white blood cells were assessed by the DNA comet assay. The plasma concentration of extracellular DNA was fluorometrically determined using a QuantiTTM HS DNA Assay Kit (Invitrogen, USA. That of 8hydroxy2deoxyguanosine was estimated by enzyme immunoassay employing an 8hydroxy2deoxyGuanosine EIA Kit (Cayman Chemical, USA. The levels of cas

A polymorphism in AGT and AGTR1 gene is associated with lead-related high blood pressure.

Science.gov (United States)

Kim, Hyung-Ki; Lee, Hwayoung; Kwon, Jun-Tack; Kim, Hak-Jae

2015-12-01

We investigated the association of polymorphisms in two renin-angiotensin system-related genes, expressed as angiotensinogen (AGT) and angiotensin II type 1 receptor (AGTR1), with blood lead levels and lead-related blood pressure in lead-exposed male workers in Korea. A cross-sectional study involving 808 lead-exposed male workers in Korea was conducted using a restriction fragment length polymorphism-based strategy to differentiate the various genotypes of polymorphisms in the AGT and AGTR1 genes. The association of clinical characteristics with genotypes as modifiers was estimated after adjustment for age, smoking status, drinking status, body mass index and job duration of each subject. Genotype and allele frequencies of the M235T polymorphism in AGT were associated with lead-related high blood pressure status. Moreover, blood lead levels were associated with allele frequencies of the AGT M235T polymorphism. These results suggested that the M/M genotype and M allele of AGT are risk factors for lead-related high blood pressure. © The Author(s) 2014.

Sorting white blood cells in microfabricated arrays

Science.gov (United States)

Castelino, Judith Andrea Rose

Fractionating white cells in microfabricated arrays presents the potential for detecting cells with abnormal adhesive or deformation properties. A possible application is separating nucleated fetal red blood cells from maternal blood. Since fetal cells are nucleated, it is possible to extract genetic information about the fetus from them. Separating fetal cells from maternal blood would provide a low cost noninvasive prenatal diagnosis for genetic defects, which is not currently available. We present results showing that fetal cells penetrate further into our microfabricated arrays than adult cells, and that it is possible to enrich the fetal cell fraction using the arrays. We discuss modifications to the array which would result in further enrichment. Fetal cells are less adhesive and more deformable than adult white cells. To determine which properties limit penetration, we compared the penetration of granulocytes and lymphocytes in arrays with different etch depths, constriction size, constriction frequency, and with different amounts of metabolic activity. The penetration of lymphocytes and granulocytes into constrained and unconstrained arrays differed qualitatively. In constrained arrays, the cells were activated by repeated shearing, and the number of cells stuck as a function of distance fell superexponentially. In unconstrained arrays the number of cells stuck fell slower than an exponential. We attribute this result to different subpopulations of cells with different sticking parameters. We determined that penetration in unconstrained arrays was limited by metabolic processes, and that when metabolic activity was reduced penetration was limited by deformability. Fetal cells also contain a different form of hemoglobin with a higher oxygen affinity than adult hemoglobin. Deoxygenated cells are paramagnetic and are attracted to high magnetic field gradients. We describe a device which can separate cells using 10 μm magnetic wires to deflect the paramagnetic

Separation of cancer cells from white blood cells by pinched flow fractionation

DEFF Research Database (Denmark)

Jensen, Marie Pødenphant; Ashley, Neil; Koprowska, Kamila

2015-01-01

In this paper, the microfluidic size-separation technique pinched flow fractionation (PFF) is used to separate cancer cells from white blood cells (WBCs). The cells are separated at efficiencies above 90% for both cell types. Circulating tumor cells (CTCs) are found in the blood of cancer patients...... and can form new tumors. CTCs are rare cells in blood, but they are important for the understanding of metastasis. There is therefore a high interest in developing a method for the enrichment of CTCs from blood samples, which also enables further analysis of the separated cells. The separation...

Ligand-Modified Human Serum Albumin Nanoparticles for Enhanced Gene Delivery.

Science.gov (United States)

Look, Jennifer; Wilhelm, Nadine; von Briesen, Hagen; Noske, Nadja; Günther, Christine; Langer, Klaus; Gorjup, Erwin

2015-09-08

The development of nonviral gene delivery systems is a great challenge to enable safe gene therapy. In this study, ligand-modified nanoparticles based on human serum albumin (HSA) were developed and optimized for an efficient gene therapy. Different glutaraldehyde cross-linking degrees were investigated to optimize the HSA nanoparticles for gene delivery. The peptide sequence arginine-glycine-aspartate (RGD) and the HIV-1 transactivator of transduction sequence (Tat) are well-known as promising targeting ligands. Plasmid DNA loaded HSA nanoparticles were covalently modified on their surface with these different ligands. The transfection potential of the obtained plasmid DNA loaded RGD- and Tat-modified nanoparticles was investigated in vitro, and optimal incubation conditions for these preparations were studied. It turned out that Tat-modified HSA nanoparticles with the lowest cross-linking degree of 20% showed the highest transfection potential. Taken together, ligand-functionalized HSA nanoparticles represent promising tools for efficient and safe gene therapy.

Gene expression signatures in peripheral blood cells from Japanese women exposed to environmental cadmium

International Nuclear Information System (INIS)

Dakeshita, Satoru; Kawai, Tomoko; Uemura, Hirokazu; Hiyoshi, Mineyoshi; Oguma, Etsuko; Horiguchi, Hyogo; Kayama, Fujio; Aoshima, Keiko; Shirahama, Satoshi; Rokutan, Kazuhito; Arisawa, Kokichi

2009-01-01

The objective of this study was to examine the effects of environmental cadmium (Cd) exposure on the gene expression profile of peripheral blood cells, using an original oligoDNA microarray. The study population consisted of 20 female residents in a Cd-polluted area (Cd-exposed group) and 20 female residents in a non-Cd-polluted area individually matched for age (control group). The mRNA levels in Cd-exposed subjects were compared with those in respective controls, using a microarray containing oligoDNA probes for 1867 genes. Median Cd concentrations in blood (3.55 μg/l) and urine (8.25 μg/g creatinine) from the Cd-exposed group were 2.4- and 1.9-times higher than those of the control group, respectively. Microarray analysis revealed that the Cd-exposed group significantly up-regulated 137 genes and down-regulated 80 genes, compared with the control group. The Ingenuity Pathway Analysis Application (IPA) revealed that differentially expressed genes were likely to modify oxidative stress and mitochondria-dependent apoptosis pathways. Among differentially expressed genes, the expression of five genes was positively correlated with Cd concentrations in blood or urine. Quantitative real-time PCR (RT-PCR) analysis validated the significant up-regulation of CASP9, TNFRSF1B, GPX3, HYOU1, SLC3A2, SLC19A1, SLC35A4 and ITGAL, and down-regulation of BCL2A1 and COX7B. After adjustment for differences in the background characteristics of the two groups, we finally identified seven Cd-responsive genes (CASP9, TNFRSF1B, GPX3, SLC3A2, ITGAL, BCL2A1, and COX7B), all of which constituted a network that controls oxidative stress response by IPA. These seven genes may be marker genes useful for the health risk assessment of chronic low level exposure to Cd

Diffusion tensor imaging of brain white matter in Huntington gene mutation individuals

Directory of Open Access Journals (Sweden)

Roberta Arb Saba

Full Text Available ABSTRACT Objective To evaluate the role of the involvement of white matter tracts in huntingtin gene mutation patients as a potential biomarker of the progression of the disease. Methods We evaluated 34 participants (11 symptomatic huntingtin gene mutation, 12 presymptomatic huntingtin gene mutation, and 11 controls. We performed brain magnetic resonance imaging to assess white matter integrity using diffusion tensor imaging, with measurement of fractional anisotropy. Results We observed a significant decrease of fractional anisotropy in the cortical spinal tracts, corona radiate, corpus callosum, external capsule, thalamic radiations, superior and inferior longitudinal fasciculus, and inferior frontal-occipital fasciculus in the Huntington disease group compared to the control and presymptomatic groups. Reduction of fractional anisotropy is indicative of a degenerative process and axonal loss. There was no statistically significant difference between the presymptomatic and control groups. Conclusion White matter integrity is affected in huntingtin gene mutation symptomatic individuals, but other studies with larger samples are required to assess its usefulness in the progression of the neurodegenerative process.

A microfluidic chip for direct and rapid trapping of white blood cells from whole blood

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Chen, Jingdong; Chen, Di; Yuan, Tao; Xie, Yao; Chen, Xiang

2013-01-01

Blood analysis plays a major role in medical and science applications and white blood cells (WBCs) are an important target of analysis. We proposed an integrated microfluidic chip for direct and rapid trapping WBCs from whole blood. The microfluidic chip consists of two basic functional units: a winding channel to mix and arrays of two-layer trapping structures to trap WBCs. Red blood cells (RBCs) were eliminated through moving the winding channel and then WBCs were trapped by the arrays of trapping structures. We fabricated the PDMS (polydimethylsiloxane) chip using soft lithography and determined the critical flow velocities of tartrazine and brilliant blue water mixing and whole blood and red blood cell lysis buffer mixing in the winding channel. They are 0.25 μl/min and 0.05 μl/min, respectively. The critical flow velocity of the whole blood and red blood cell lysis buffer is lower due to larger volume of the RBCs and higher kinematic viscosity of the whole blood. The time taken for complete lysis of whole blood was about 85 s under the flow velocity 0.05 μl/min. The RBCs were lysed completely by mixing and the WBCs were trapped by the trapping structures. The chip trapped about 2.0 × 103 from 3.3 × 103 WBCs. PMID:24404026

Impact of blood collection and processing on peripheral blood gene expression profiling in type 1 diabetes.

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Yip, Linda; Fuhlbrigge, Rebecca; Atkinson, Mark A; Fathman, C Garrison

2017-08-18

The natural history of type 1 diabetes (T1D) is challenging to investigate, especially as pre-diabetic individuals are difficult to identify. Numerous T1D consortia have been established to collect whole blood for gene expression analysis from individuals with or at risk to develop T1D. However, with no universally accepted protocol for their collection, differences in sample processing may lead to variances in the results. Here, we examined whether the choice of blood collection tube and RNA extraction kit leads to differences in the expression of genes that are changed during the progression of T1D, and if these differences could be minimized by measuring gene expression directly from the lysate of whole blood. Microarray analysis showed that the expression of 901 genes is highly influenced by sample processing using the PAXgene versus the Tempus system. These included a significant number of lymphocyte-specific genes and genes whose expression has been reported to differ in the peripheral blood of at-risk and T1D patients compared to controls. We showed that artificial changes in gene expression occur when control and T1D samples were processed differently. The sample processing-dependent differences in gene expression were largely due to loss of transcripts during the RNA extraction step using the PAXgene system. The majority of differences were not observed when gene expression was measured in whole blood lysates prepared from blood collected in PAXgene and Tempus tubes. We showed that the gene expression profile of samples processed using the Tempus system is more accurate than that of samples processed using the PAXgene system. Variation in sample processing can result in misleading changes in gene expression. However, these differences can be minimized by measuring gene expression directly in whole blood lysates.

Indium-111 oxine labelling of white blood cells

International Nuclear Information System (INIS)

Lavender, J.P.; Silvester, D.J.; Goldman, J.; Hammersmith Hospital, London

1978-01-01

Following work done by Professor John McAfee and Mathew Thakur at the MRS Cyclotron Unit a method is available for labelling cells with indium-111 which results in a stable intracellular marker. The method uses indium-111-8 hydroxyquinoline (111In oxine) which is a lipoid soluble complex which goes across the cell membrane and results in the deposition of indium into various subcellular structures. It has been applied to various preparations of white cells, platelets and also malignant cells. Autologous granulocytes have been used to identify inflammatory lesions in 35 patients. By similar means autologous lymphocytes can also be labelled and reinfused. Lymphocytes have been shown in animals to circulate from the blood via the lymphatic system and then returning to the blood once more. The same phenomenon can be seen in man using indium labelled lymphocytes. Lymph nodes become visible at between 12 and 18 hours and recirculation of labelled cells can be shown on the blood activity curves. Certain problems arise concerning cell behaviour after labelling which appear due to irradiation of cells rather than chemical toxicity. (author)

Blood Pressure Control in Aging Predicts Cerebral Atrophy Related to Small-Vessel White Matter Lesions

Directory of Open Access Journals (Sweden)

Kyle C. Kern

2017-05-01

Full Text Available Cerebral small-vessel damage manifests as white matter hyperintensities and cerebral atrophy on brain MRI and is associated with aging, cognitive decline and dementia. We sought to examine the interrelationship of these imaging biomarkers and the influence of hypertension in older individuals. We used a multivariate spatial covariance neuroimaging technique to localize the effects of white matter lesion load on regional gray matter volume and assessed the role of blood pressure control, age and education on this relationship. Using a case-control design matching for age, gender, and educational attainment we selected 64 participants with normal blood pressure, controlled hypertension or uncontrolled hypertension from the Northern Manhattan Study cohort. We applied gray matter voxel-based morphometry with the scaled subprofile model to (1 identify regional covariance patterns of gray matter volume differences associated with white matter lesion load, (2 compare this relationship across blood pressure groups, and (3 relate it to cognitive performance. In this group of participants aged 60–86 years, we identified a pattern of reduced gray matter volume associated with white matter lesion load in bilateral temporal-parietal regions with relative preservation of volume in the basal forebrain, thalami and cingulate cortex. This pattern was expressed most in the uncontrolled hypertension group and least in the normotensives, but was also more evident in older and more educated individuals. Expression of this pattern was associated with worse performance in executive function and memory. In summary, white matter lesions from small-vessel disease are associated with a regional pattern of gray matter atrophy that is mitigated by blood pressure control, exacerbated by aging, and associated with cognitive performance.

Construction of full-length cDNA library of white flower Salvia ...

African Journals Online (AJOL)

In order to screen and isolate secondary metabolite biosynthesis related gene, we construct a cDNA library of white flower Salvia miltiorrhiza bge. f.alba. High quality of total RNA was successfully isolated from roots of white flower S. miltiorrhiza using modified CTAB method. Double strand cDNA was cloned into pDNR-LIB ...

Gene expression differences between PAXgene and Tempus blood RNA tubes are highly reproducible between independent samples and biobanks.

Science.gov (United States)

Skogholt, Anne Heidi; Ryeng, Einar; Erlandsen, Sten Even; Skorpen, Frank; Schønberg, Svanhild A; Sætrom, Pål

2017-03-23

Gene expression profiling from blood is sensitive to technology choices. For example, the main blood RNA collection systems-the PAXgene and Tempus tubes-differently influence RNA expression signatures. The aim of this study was to establish a common RNA isolation protocol for these two systems and investigate if it could reduce the differences in gene expression between them. We collected identical blood samples on the PAXgene and Tempus systems and retrieved blood samples from two independent biobanks-NOWAC and HUNT3-which are based on PAXgene and Tempus, respectively. High-quality RNA was extracted from both sampling systems by using their original protocols and our common modified protocol, and were profiled on Illumina microarrays. Regardless of the protocol used, we found most of the measured transcripts to be differently affected by the two sampling systems. However, our modified protocol reduced the number of transcripts that were significantly differentially expressed between PAXgene and Tempus by approximately 50%. Expression differences between PAXgene and Tempus were highly reproducible both between protocols and between different independent sample sets (Pearson correlation 0.563-0.854 across 47323 probes). Moreover, the modified protocol increased the microRNA output of the system with lowest microRNA yield, the PAXgene system. Most transcripts are affected by the choice of sampling system, but these effects are highly reproducible between independent samples. We propose that by running a control experiment with samples on both systems in parallel with biologically relevant samples, researchers may adjust for technical differences between the sampling systems.

Segmentation of white blood cells and comparison of cell morphology by linear and naïve Bayes classifiers.

Science.gov (United States)

Prinyakupt, Jaroonrut; Pluempitiwiriyawej, Charnchai

2015-06-30

Blood smear microscopic images are routinely investigated by haematologists to diagnose most blood diseases. However, the task is quite tedious and time consuming. An automatic detection and classification of white blood cells within such images can accelerate the process tremendously. In this paper we propose a system to locate white blood cells within microscopic blood smear images, segment them into nucleus and cytoplasm regions, extract suitable features and finally, classify them into five types: basophil, eosinophil, neutrophil, lymphocyte and monocyte. Two sets of blood smear images were used in this study's experiments. Dataset 1, collected from Rangsit University, were normal peripheral blood slides under light microscope with 100× magnification; 555 images with 601 white blood cells were captured by a Nikon DS-Fi2 high-definition color camera and saved in JPG format of size 960 × 1,280 pixels at 15 pixels per 1 μm resolution. In dataset 2, 477 cropped white blood cell images were downloaded from CellaVision.com. They are in JPG format of size 360 × 363 pixels. The resolution is estimated to be 10 pixels per 1 μm. The proposed system comprises a pre-processing step, nucleus segmentation, cell segmentation, feature extraction, feature selection and classification. The main concept of the segmentation algorithm employed uses white blood cell's morphological properties and the calibrated size of a real cell relative to image resolution. The segmentation process combined thresholding, morphological operation and ellipse curve fitting. Consequently, several features were extracted from the segmented nucleus and cytoplasm regions. Prominent features were then chosen by a greedy search algorithm called sequential forward selection. Finally, with a set of selected prominent features, both linear and naïve Bayes classifiers were applied for performance comparison. This system was tested on normal peripheral blood smear slide images from two datasets. Two sets

Prognosis of white-coat and masked hypertension: International Database of HOme blood pressure in relation to Cardiovascular Outcome.

Science.gov (United States)

Stergiou, George S; Asayama, Kei; Thijs, Lutgarde; Kollias, Anastasios; Niiranen, Teemu J; Hozawa, Atsushi; Boggia, José; Johansson, Jouni K; Ohkubo, Takayoshi; Tsuji, Ichiro; Jula, Antti M; Imai, Yutaka; Staessen, Jan A

2014-04-01

Home blood pressure monitoring is useful in detecting white-coat and masked hypertension and is recommended for patients with suspected or treated hypertension. The prognostic significance of white-coat and masked hypertension detected by home measurement was investigated in 6458 participants from 5 populations enrolled in the International Database of HOme blood pressure in relation to Cardiovascular Outcomes. During a median follow-up of 8.3 years, 714 fatal plus nonfatal cardiovascular events occurred. Among untreated subjects (n=5007), cardiovascular risk was higher in those with white-coat hypertension (adjusted hazard ratio 1.42; 95% CI [1.06-1.91]; P=0.02), masked hypertension (1.55; 95% CI [1.12-2.14]; P<0.01) and sustained hypertension (2.13; 95% CI [1.66-2.73]; P<0.0001) compared with normotensive subjects. Among treated patients (n=1451), the cardiovascular risk did not differ between those with high office and low home blood pressure (white-coat) and treated controlled subjects (low office and home blood pressure; 1.16; 95% CI [0.79-1.72]; P=0.45). However, treated subjects with masked hypertension (low office and high home blood pressure; 1.76; 95% CI [1.23-2.53]; P=0.002) and uncontrolled hypertension (high office and home blood pressure; 1.40; 95% CI [1.02-1.94]; P=0.04) had higher cardiovascular risk than treated controlled patients. In conclusion, white-coat hypertension assessed by home measurements is a cardiovascular risk factor in untreated but not in treated subjects probably because the latter receive effective treatment on the basis of their elevated office blood pressure. In contrast, masked uncontrolled hypertension is associated with increased cardiovascular risk in both untreated and treated patients, who are probably undertreated because of their low office blood pressure.

Diagnosis of infection by preoperative scintigraphy with indium-labeled white blood cells

International Nuclear Information System (INIS)

Wukich, D.K.; Abreu, S.H.; Callaghan, J.J.; Van Nostrand, D.; Savory, C.G.; Eggli, D.F.; Garcia, J.E.; Berrey, B.H.

1987-01-01

Scintigraphy with indium-labeled white blood cells has been reported to be sensitive and specific in the diagnosis of low-grade sepsis of the musculoskeletal system. We reviewed the records of fifty patients who had suspected osteomyelitis or suspected infection about a total joint prosthesis and who underwent scintigraphy with technetium-99m methylene diphosphonate and scintigraphy with indium-111 oxine-labeled white blood cells before an open surgical procedure. Any patient who received preoperative antibiotics was not included in the study. For all of the patients, gram-stain examination of smears, evaluation of a culture of material from the operative site, and histological examination were done. The patients were divided into two groups. Group I was composed of twenty-four patients, each of whom had a prosthesis in place and complained of pain. Group II was composed of twenty-six patients for whom a diagnosis of chronic osteomyelitis had to be considered. With the indium scans alone, there was only one false-negative result (in Group II), but there were eighteen false-positive results (eight patients in Group II and ten patients in Group I). Although scintigraphy with indium-labeled white blood cells is quite sensitive, it is not specific in detecting chronic osteomyelitis; a negative scan should be considered highly suggestive that osteomyelitis is not present. Specificity can be increased by interpreting the indium scan in conjunction with the technetium scan

Diagnosis of arterial prosthetic graft infection by 111In oxine white blood cell scans

International Nuclear Information System (INIS)

McKeown, P.P.; Miller, D.C.; Jamieson, S.W.; Mitchell, R.S.; Reitz, B.A.; Olcott, C.; Mehigan, J.T.; Silberstein, R.J.; McDougall, I.R.

1982-01-01

Early and accurate diagnosis of infected prosthetic arterial grafts is difficult, despite the application of diverse diagnostic modalities. Delay in making the diagnosis is largely responsible for the high amputation and mortality rates associated with this complication. In nine patients with suspected graft infections, 111 In white blood cell scanning was useful and accurate. Graft infection was proved in five cases and ruled out in three. One false-positive scan was due to a sigmoid diverticular abscess overlying the graft. 111 In white blood cell scans may improve the accuracy of diagnosing infected prosthetic grafts, which may result in better limb and patient salvage rates

Dried blood spots of pooled samples for RHD gene screening in blood donors of mixed ancestry.

Science.gov (United States)

Silva-Malta, M C F; Araujo, N C Fidélis; Vieira, O V Neves; Schmidt, L Cayres; Gonçalves, P de Cassia; Martins, M Lobato

2015-10-01

In this study, we present a strategy for RHD gene screening based on real-time polymerase chain reaction (PCR) using dried blood spots of pooled samples. Molecular analysis of blood donors may be used to detect RHD variants among the presumed D-negative individuals. RHD genotyping using pooled samples is a strategy to test a large number of samples at a more reasonable cost. RHD gene detection based on real-time PCR using dried blood spots of pooled samples was standardised and used to evaluate 1550 Brazilian blood donors phenotyped as RhD-negative. Positive results were re-evaluated by retesting single samples using real-time PCR and conventional multiplex PCR to amplify five RHD-specific exons. PCR-sequence-specific primers was used to amplify RHDψ allele. We devised a strategy for RHD gene screening using dried blood spots of five pooled samples. Among 1550 serologically D-negative blood donors, 58 (3.74%) had the RHD gene. The non-functional RHDψ allele was detected in 47 samples (3.02%). The present method is a promising strategy to detect the RHD gene among presumed RhD-negative blood donors, particularly for populations with African ancestry. © 2015 British Blood Transfusion Society.

Four-Parameter white blood cell differential counting based on light scattering measurements

NARCIS (Netherlands)

Terstappen, Leonardus Wendelinus Mathias Marie; de Grooth, B.G.; Visscher, K.; Kouterik, F.A.; Greve, Jan

1988-01-01

Measurement of the depolarized orthogonal light scattering in flow cytometry enables one to discriminate human eosinephilic granulocytes from neutrophilic granulocytes. We use this method to perform a four-parameter differential white blood cell analysis. A simple flow cytometer was built equipped

White blood cell segmentation by color-space-based k-means clustering.

Science.gov (United States)

Zhang, Congcong; Xiao, Xiaoyan; Li, Xiaomei; Chen, Ying-Jie; Zhen, Wu; Chang, Jun; Zheng, Chengyun; Liu, Zhi

2014-09-01

White blood cell (WBC) segmentation, which is important for cytometry, is a challenging issue because of the morphological diversity of WBCs and the complex and uncertain background of blood smear images. This paper proposes a novel method for the nucleus and cytoplasm segmentation of WBCs for cytometry. A color adjustment step was also introduced before segmentation. Color space decomposition and k-means clustering were combined for segmentation. A database including 300 microscopic blood smear images were used to evaluate the performance of our method. The proposed segmentation method achieves 95.7% and 91.3% overall accuracy for nucleus segmentation and cytoplasm segmentation, respectively. Experimental results demonstrate that the proposed method can segment WBCs effectively with high accuracy.

Development of an SPR imaging biosensor for determination of cathepsin G in saliva and white blood cells

International Nuclear Information System (INIS)

Gorodkiewicz, E.; Wojtulewski, K.; Regulska, E.

2011-01-01

Cathepsin G (CatG) is an endopeptidase that is associated with the early immune response. The synthetic compound cathepsin G inhibitor I (CGI-I) was tested for its ability to inhibit the activity of CatG via a new surface plasmon resonance imaging assay. CGI-I was immobilized on the gold surface of an SPR sensor that was first modified with 1-octadecanethiol. A concentration of CGI-I equal to 4.0 μg.mL -1 and a pH of 8.0 were found to give the best results. The dynamic response of the sensor ranges from 0. 25 to 1. 5 ng.mL -1 , and the detection limit is 0. 12 ng.mL -1 . The sensor was applied to detect CatG in human saliva and white blood cells. (author)

Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients are associated with improved clinical response to methotrexate therapy.

Science.gov (United States)

Tchetina, Elena V; Demidova, Natalia V; Markova, Galina A; Taskina, Elena A; Glukhova, Svetlana I; Karateev, Dmitry E

2017-10-01

To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction. The protein concentrations in peripheral blood mononuclear cells were quantified using enzyme-linked immunosorbent assay. Receiver operating characteristic curve analyses were used to suggest thresholds that were associated with the prediction of the response. Decreases in the disease activity at the end of the study were accompanied by significant increases in joint space narrowing score (JSN). Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1) and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen joint count were noted at baseline. The baseline tumor necrosis factor (TNF)α gene expression was positively correlated with JSN at the end of the follow-up, whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were correlated with the ΔDAS28 values. Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity. Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to MTX therapy. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency.

Science.gov (United States)

Shaw, Kit L; Garabedian, Elizabeth; Mishra, Suparna; Barman, Provaboti; Davila, Alejandra; Carbonaro, Denise; Shupien, Sally; Silvin, Christopher; Geiger, Sabine; Nowicki, Barbara; Smogorzewska, E Monika; Brown, Berkley; Wang, Xiaoyan; de Oliveira, Satiro; Choi, Yeong; Ikeda, Alan; Terrazas, Dayna; Fu, Pei-Yu; Yu, Allen; Fernandez, Beatriz Campo; Cooper, Aaron R; Engel, Barbara; Podsakoff, Greg; Balamurugan, Arumugam; Anderson, Stacie; Muul, Linda; Jagadeesh, G Jayashree; Kapoor, Neena; Tse, John; Moore, Theodore B; Purdy, Ken; Rishi, Radha; Mohan, Kathey; Skoda-Smith, Suzanne; Buchbinder, David; Abraham, Roshini S; Scharenberg, Andrew; Yang, Otto O; Cornetta, Kenneth; Gjertson, David; Hershfield, Michael; Sokolic, Rob; Candotti, Fabio; Kohn, Donald B

2017-05-01

Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1-2.6) and granulocytes (VCN = 0.01-0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. ClinicalTrials.gov NCT00794508. Food and Drug Administration Office of Orphan Product Development award, RO1 FD003005; NHLBI awards, PO1 HL73104 and Z01 HG000122; UCLA

Clinical efficacy of gene-modified stem cells in adenosine deaminase–deficient immunodeficiency

Science.gov (United States)

Shaw, Kit L.; Garabedian, Elizabeth; Mishra, Suparna; Barman, Provaboti; Davila, Alejandra; Carbonaro, Denise; Shupien, Sally; Silvin, Christopher; Geiger, Sabine; Nowicki, Barbara; Smogorzewska, E. Monika; Brown, Berkley; Wang, Xiaoyan; de Oliveira, Satiro; Choi, Yeong; Ikeda, Alan; Terrazas, Dayna; Fu, Pei-Yu; Yu, Allen; Fernandez, Beatriz Campo; Cooper, Aaron R.; Engel, Barbara; Podsakoff, Greg; Balamurugan, Arumugam; Anderson, Stacie; Muul, Linda; Jagadeesh, G. Jayashree; Kapoor, Neena; Tse, John; Moore, Theodore B.; Purdy, Ken; Rishi, Radha; Mohan, Kathey; Skoda-Smith, Suzanne; Buchbinder, David; Abraham, Roshini S.; Scharenberg, Andrew; Yang, Otto O.; Cornetta, Kenneth; Gjertson, David; Hershfield, Michael; Sokolic, Rob; Candotti, Fabio

2017-01-01

BACKGROUND. Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase–deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS. Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation. Subjects were followed from 33 to 84 months at the time of data analysis. Safety of the procedure was assessed by recording the number of adverse events. Efficacy was assessed by measuring engraftment of gene-modified hematopoietic stem/progenitor cells, ADA gene expression, and immune reconstitution. RESULTS. With the exception of the oldest subject (15 years old at enrollment), all subjects remained off ERT with normalized peripheral blood mononuclear cell (PBMC) ADA activity, improved lymphocyte numbers, and normal proliferative responses to mitogens. Three of nine subjects were able to discontinue intravenous immunoglobulin replacement therapy. The MND-ADA vector was persistently detected in PBMCs (vector copy number [VCN] = 0.1–2.6) and granulocytes (VCN = 0.01–0.3) through the most recent visits at the time of this writing. No patient has developed a leukoproliferative disorder or other vector-related clinical complication since transplant. CONCLUSION. These results demonstrate clinical therapeutic efficacy from gene therapy for ADA-deficient SCID, with an excellent clinical safety profile. TRIAL REGISTRATION. ClinicalTrials.gov NCT00794508. FUNDING. Food and Drug Administration Office of Orphan Product

Modifier genes: Moving from pathogenesis to therapy.

Science.gov (United States)

McCabe, Edward R B

2017-09-01

This commentary will focus on how we can use our knowledge about the complexity of human disease and its pathogenesis to identify novel approaches to therapy. We know that even for single gene Mendelian disorders, patients with identical mutations often have different presentations and outcomes. This lack of genotype-phenotype correlation led us and others to examine the roles of modifier genes in the context of biological networks. These investigations have utilized vertebrate and invertebrate model organisms. Since one of the goals of research on modifier genes and networks is to identify novel therapeutic targets, the challenges to patient access and compliance because of the high costs of medications for rare genetic diseases must be recognized. A recent article explored protective modifiers, including plastin 3 (PLS3) and coronin 1C (CORO1C), in spinal muscular atrophy (SMA). SMA is an autosomal recessive deficit of survival motor neuron protein (SMN) caused by mutations in SMN1. However, the severity of SMA is determined primarily by the number of SMN2 copies, and this results in significant phenotypic variability. PLS3 was upregulated in siblings who were asymptomatic compared with those who had SMA2 or SMA3, but identical homozygous SMN1 deletions and equal numbers of SMN2 copies. CORO1C was identified by interrogation of the PLS3 interactome. Overexpression of these proteins rescued endocytosis in SMA models. In addition, antisense RNA for upregulation of SMN2 protein expression is being developed as another way of modifying the SMA phenotype. These investigations suggest the practical application of protective modifiers to rescue SMA phenotypes. Other examples of the potential therapeutic value of novel protective modifiers will be discussed, including in Duchenne muscular dystrophy and glycerol kinase deficiency. This work shows that while we live in an exciting era of genomic sequencing, a functional understanding of biology, the impact of its

Effect of interval training program on white blood cell count in the ...

African Journals Online (AJOL)

Objective: Elevated white blood cell (WBC) count is considered to be prospectively and positively associated with cardiovascular diseases, particularly hypertension. Also, the positive role of exercise in the management of hypertension has been well and long established. However the relationship between WBC count and ...

Detection of EPO gene doping in blood.

Science.gov (United States)

Neuberger, Elmo W I; Jurkiewicz, Magdalena; Moser, Dirk A; Simon, Perikles

2012-11-01

Gene doping--or the abuse of gene therapy--will continue to threaten the sports world. History has shown that progress in medical research is likely to be abused in order to enhance human performance. In this review, we critically discuss the progress and the risks associated with the field of erythropoietin (EPO) gene therapy and its applicability to EPO gene doping. We present typical vector systems that are employed in ex vivo and in vivo gene therapy trials. Due to associated risks, gene doping is not a feasible alternative to conventional EPO or blood doping at this time. Nevertheless, it is well described that about half of the elite athlete population is in principle willing to risk its health to gain a competitive advantage. This includes the use of technologies that lack safety approval. Sophisticated detection approaches are a prerequisite for prevention of unapproved and uncontrolled use of gene therapy technology. In this review, we present current detection approaches for EPO gene doping, with a focus on blood-based direct and indirect approaches. Gene doping is detectable in principle, and recent DNA-based detection strategies enable long-term detection of transgenic DNA (tDNA) following in vivo gene transfer. Copyright © 2012 John Wiley & Sons, Ltd.

Differential gene expresison in umbilical cord blood and maternal peripheral blood

Czech Academy of Sciences Publication Activity Database

Merkerová, M.; Vasiková, A.; Bruchová, H.; Líbalová, Helena; Topinka, Jan; Balaščak, I.; Šrám, Radim; Brdička, R.

2009-01-01

Roč. 83, č. 3 (2009), s. 183-190 ISSN 0902-4441 R&D Projects: GA MŠk 2B06088 Institutional research plan: CEZ:AV0Z50390512 Keywords : gene expression * umbilical cord blood * peripheral blood Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.345, year: 2009

Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: Correlation with various leukemias and abnormal megakaryocytopoiesis

International Nuclear Information System (INIS)

Lapidot-Lifson, Y.; Prody, C.A.; Ginzberg, D.; Meytes, D.; Zakut, H.; Soreq, H.

1989-01-01

To study the yet unknown role of the ubiquitous family of cholinesterases (ChoEases) in developing blood cells, the recently isolated cDNAs encoding human acetylcholinesterase and butyrylcholinesterase were used in blot hybridization with peripheral blood DNA from various leukemic patients. Hybridization signals and modified restriction patterns were observed with both cDNA probes in 4 of the 16 leukemia DNA preparations examined. These reflected the amplification of the corresponding AcCho-Ease and BtChoEase genes (ACHE and CHE) and alteration in their structure. Parallel analysis of 30 control samples revealed nonpolymorphic, much weaker hybridization signals for each of the probes. In view of previous reports on the effect of acetylcholine analogs and ChoEase inhibitors in the induction of megakaryocytopoiesis and production of platelets in the mouse. The authors further searched for such phenomena in nonleukemic patients with platelet production disorders. Amplifications of both ACHE and CHE genes were found in 2 of the 4 patients so far examined. Pronounced coamplification of these two related but distinct genes in correlation with pathological production of blood cells suggests a functional role for members of the ChoEase family in megakaryocytopoiesis and raises the question whether the coamplification of these genes could be casually involved in the etiology of hemocytopoietic disorders

False positive paediatric labelled white blood cell study

International Nuclear Information System (INIS)

Beveridge, N.; Bennett, E.; Thomas, P.

2002-01-01

Full text: An eight-month-old female presented for a technetium labelled white blood cell study (LWBC) to exclude an intra-abdominal abscess. Born premature, the child had surgery to repair a perforated bowel and had repeated presentations with diarrhoea, fevers, a tender right upper quadrant and a raised leucocyte count. Multiple imaging modalities failed to demonstrate recurrent bowel perforation, ischaemia or an intra-abdominal mass. A LWBC study was performed with whole body imaging at 1 and 5 hours post re-injection of the radiolabelled blood. No abnormal uptake was visualised in the abdomen but abnormal white cell accumulation was noted in the right hind foot and the length of the right lower leg. This activity appeared to lie along the course of the right tibia. Plain X-ray demonstrated no evidence of tibial osteomyelitis. Concern that the LWBC may be falsely negative in a patient on antibiotics, a gallium scan was immediately performed to re-examine the abdomen. The whole body gallium images demonstrated normal physiological uptake in the abdomen and no evidence of infection in the right leg. The patient had no clinical features to support right leg pathology. The abnormal LWBC localisation in the right lower leg/foot was therefore falsely positive. The most likely explanation is increased activation of the autologous LWBC by 'rough' handling during difficult venesection and re-injection through small veins and needles/cannulas. The slow flow through the veins draining the foot injection site would contribute to margination in these vessel walls. This is a potential cause for false positive LWBC studies- with significant implications for patient care. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

EFFECT OF SAPPAN WOOD (Caesalpinnia sappan L EXTRACT ON BLOOD GLUCOSE LEVEL IN WHITE RATS

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Saefudin Saefudin

2016-05-01

Full Text Available Sappan wood or kayu secang (Caesalpinia sappan L. was reported of having medicinal properties, such as natural antioxidant, relieve vomiting of blood, and mix of ingredients for malaria drugs. The research was conducted to study the influence of ethanol extract from sappan wood on blood glucose level of white rats. The study of the blood glucose level in rats was carried out by using glucose tolerance method. It was measured by Refloluxs (Accutrend GC with Chloropropamide 50 mg/200 g BW (Body weight as positive control. The ethanol extracts were used in various concentrations 10, 20, 30, 40 and 50 mg/200 g BW per-oral and was observed every hour, beginning one hour before to 7 hours after the extract being administered. The results showed that treatment of ethanol extract of sappan wood by administer doses gave remarkable effect on the blood glucose level in white rat. It reduced the glucose level in the blood compared to the negative and positive control. Treatment of dose 30 mg/200 g BW gave similar effect to positive controls, while a dose of 50 mg/200 g BW gave lower blood glucose level (93 mg/dl than the positive controls.

De Novo Assembly of the Donkey White Blood Cell Transcriptome and a Comparative Analysis of Phenotype-Associated Genes between Donkeys and Horses.

Science.gov (United States)

Xie, Feng-Yun; Feng, Yu-Long; Wang, Hong-Hui; Ma, Yun-Feng; Yang, Yang; Wang, Yin-Chao; Shen, Wei; Pan, Qing-Jie; Yin, Shen; Sun, Yu-Jiang; Ma, Jun-Yu

2015-01-01

Prior to the mechanization of agriculture and labor-intensive tasks, humans used donkeys (Equus africanus asinus) for farm work and packing. However, as mechanization increased, donkeys have been increasingly raised for meat, milk, and fur in China. To maintain the development of the donkey industry, breeding programs should focus on traits related to these new uses. Compared to conventional marker-assisted breeding plans, genome- and transcriptome-based selection methods are more efficient and effective. To analyze the coding genes of the donkey genome, we assembled the transcriptome of donkey white blood cells de novo. Using transcriptomic deep-sequencing data, we identified 264,714 distinct donkey unigenes and predicted 38,949 protein fragments. We annotated the donkey unigenes by BLAST searches against the non-redundant (NR) protein database. We also compared the donkey protein sequences with those of the horse (E. caballus) and wild horse (E. przewalskii), and linked the donkey protein fragments with mammalian phenotypes. As the outer ear size of donkeys and horses are obviously different, we compared the outer ear size-associated proteins in donkeys and horses. We identified three ear size-associated proteins, HIC1, PRKRA, and KMT2A, with sequence differences among the donkey, horse, and wild horse loci. Since the donkey genome sequence has not been released, the de novo assembled donkey transcriptome is helpful for preliminary investigations of donkey cultivars and for genetic improvement.

Blood-informative transcripts define nine common axes of peripheral blood gene expression.

Directory of Open Access Journals (Sweden)

Marcela Preininger

Full Text Available We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses. Conservation of the Axes is demonstrated in each of five additional population-based gene expression profiling studies, one of which is robustly associated with Body Mass Index in the CHDWB as well as Finnish and Australian cohorts. Furthermore, ten tightly co-regulated genes can be used to define each Axis as "Blood Informative Transcripts" (BITs, generating scores that define an individual with respect to the represented immune activity and blood physiology. We show that environmental factors, including lifestyle differences in Morocco and infection leading to active or latent tuberculosis, significantly impact specific axes, but that there is also significant heritability for the Axis scores. In the context of personalized medicine, reanalysis of the longitudinal profile of one individual during and after infection with two respiratory viruses demonstrates that specific axes also characterize clinical incidents. This mode of analysis suggests the view that, rather than unique subsets of genes marking each class of disease, differential expression reflects movement along the major normal Axes in response to environmental and genetic stimuli.

Blood-informative transcripts define nine common axes of peripheral blood gene expression.

Science.gov (United States)

Preininger, Marcela; Arafat, Dalia; Kim, Jinhee; Nath, Artika P; Idaghdour, Youssef; Brigham, Kenneth L; Gibson, Greg

2013-01-01

We describe a novel approach to capturing the covariance structure of peripheral blood gene expression that relies on the identification of highly conserved Axes of variation. Starting with a comparison of microarray transcriptome profiles for a new dataset of 189 healthy adult participants in the Emory-Georgia Tech Center for Health Discovery and Well-Being (CHDWB) cohort, with a previously published study of 208 adult Moroccans, we identify nine Axes each with between 99 and 1,028 strongly co-regulated transcripts in common. Each axis is enriched for gene ontology categories related to sub-classes of blood and immune function, including T-cell and B-cell physiology and innate, adaptive, and anti-viral responses. Conservation of the Axes is demonstrated in each of five additional population-based gene expression profiling studies, one of which is robustly associated with Body Mass Index in the CHDWB as well as Finnish and Australian cohorts. Furthermore, ten tightly co-regulated genes can be used to define each Axis as "Blood Informative Transcripts" (BITs), generating scores that define an individual with respect to the represented immune activity and blood physiology. We show that environmental factors, including lifestyle differences in Morocco and infection leading to active or latent tuberculosis, significantly impact specific axes, but that there is also significant heritability for the Axis scores. In the context of personalized medicine, reanalysis of the longitudinal profile of one individual during and after infection with two respiratory viruses demonstrates that specific axes also characterize clinical incidents. This mode of analysis suggests the view that, rather than unique subsets of genes marking each class of disease, differential expression reflects movement along the major normal Axes in response to environmental and genetic stimuli.

Nocturnal blood pressure in normotensive subjects and those with white coat, primary, and secondary hypertension.

OpenAIRE

Middeke, M.; Schrader, J.

1994-01-01

OBJECTIVE--To compare the mean nocturnal blood pressure of patients with various forms of renal and endocrine hypertension with that in patients with primary and white coat hypertension, and normal blood pressure. DESIGN--Ambulatory monitoring of blood pressure over 24 hours in a prospective study. SETTING--Two German centres for outpatients with hypertension and kidney diseases. SUBJECTS--176 normotensive subjects, 490 patients with primary hypertension including mild and severe forms, 42 wi...

Transcriptome data of peripheral white blood cells from beef heifers collected at the time of artificial insemination

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Sarah E. Dickinson

2018-06-01

Full Text Available The reproductive performance of heifers within their first breeding season influences the success of beef cattle operations. Therefore, a means to identify infertile and late breeding heifers before the start of the breeding season holds great promise for the future of the beef industry. Pubertal beef heifers were subjected to estrous synchronization and fixed time artificial insemination (FTAI. We collected peripheral blood from the heifers at the time of artificial insemination (AI and generated RNA sequencing data to characterize the transcriptome of peripheral white blood cells (PWBC. Following insemination, heifers were exposed to natural service for a defined breeding season, and pregnancy was evaluated to classify heifers into one of three groups: AI-pregnant, natural-bred (NB pregnant, and non-pregnant. The raw transcriptome data of PWBC is available on the NCBI GEO repository (GSE103628 where the reader can also find raw read counts and normalized gene expression data. The normalized data on transcript coverage can be visualized as a genome browser at HeiferFertilityRNAseq.org. Keywords: Biomarkers, Infertility, Pregnancy

Peripheral white blood cells profile of biodegradable metal implant in mice animal model

Science.gov (United States)

Paramitha, Devi; Noviana, Deni; Estuningsih, Sri; Ulum, Mokhamad Fakhrul; Nasution, Ahmad Kafrawi; Hermawan, Hendra

2015-09-01

Biocompatibility or safety of the medical device is considered important. It can be determined by blood profile examination. The aim of this study was to assess the biocompatibility of biodegradable metal implant through peripheral white blood cells (WBCs) profile approach. Forty eight male ddy mice were divided into four groups according to the materials implanted: iron wire (Fe), magnesium rod (Mg), stainless steel surgical wire (SS316L) and control with sham (K). Implants were inserted and attached onto the right femoral bone on latero-medial region. In this study, peripheral white blood cells and leukocyte differentiation were the parameters examined. The result showed that the WBCs value of all groups were decreased at the first day after implantation, increased at the 10th day and continued increasing at the 30th day of observation, except Mg group which has decreased. Neutrophil, as an inflammatory cells, was increased at the early weeks and decreased at the day-30 after surgery in all groups. Despite, these values during the observation were still within the normal range. As a conclus ion, biodegradable metal implants lead to an inflammatory reaction, with no adverse effect on WBC value found.

Peripheral white blood cells profile of biodegradable metal implant in mice animal model

Energy Technology Data Exchange (ETDEWEB)

Paramitha, Devi; Noviana, Deni, E-mail: deni@ipb.ac.id; Estuningsih, Sri [Faculty of Veterinary Medicine, Bogor Agricultural University (IPB), Bogor (Indonesia); Ulum, Mokhamad Fakhrul [Faculty of Veterinary Medicine, Bogor Agricultural University (IPB), Bogor (Indonesia); Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia (UTM), Johor Bahru (Malaysia); Nasution, Ahmad Kafrawi [Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia (UTM), Johor Bahru (Malaysia); Faculty of Engineering, Muhammadiyah University of Riau (UMRI), Pekanbaru (Indonesia); Hermawan, Hendra [Department of Mining, Metallurgical and Materials Engineering & CHU de Québec Research Center, Laval University (ULaval) (Canada)

2015-09-30

Biocompatibility or safety of the medical device is considered important. It can be determined by blood profile examination. The aim of this study was to assess the biocompatibility of biodegradable metal implant through peripheral white blood cells (WBCs) profile approach. Forty eight male ddy mice were divided into four groups according to the materials implanted: iron wire (Fe), magnesium rod (Mg), stainless steel surgical wire (SS316L) and control with sham (K). Implants were inserted and attached onto the right femoral bone on latero-medial region. In this study, peripheral white blood cells and leukocyte differentiation were the parameters examined. The result showed that the WBCs value of all groups were decreased at the first day after implantation, increased at the 10th day and continued increasing at the 30th day of observation, except Mg group which has decreased. Neutrophil, as an inflammatory cells, was increased at the early weeks and decreased at the day-30 after surgery in all groups. Despite, these values during the observation were still within the normal range. As a conclus ion, biodegradable metal implants lead to an inflammatory reaction, with no adverse effect on WBC value found.

Distribution of dearomatised white spirit in brain, blood, and fat tissue after repeated exposure of rats

DEFF Research Database (Denmark)

Lof, A.; Lam, Henrik Rye; Gullstrand, E.

1999-01-01

Petroleum products with low content of aromatics have been increasingly used during the past years. This study investigates tissue disposition of dearomatised white spirit. In addition, brain neurotransmitter concentrations were measured. Male rats were exposed by inhalation to 0, 400 (2.29 mg....../l), or 800 p.p.m. (4.58 mg/l) of dearomatised white spirit, 6 hr/day, 5 days/week up to 3 weeks. Five rats from each group were sacrificed immediately after the exposure for 1, 2, or 3 weeks and 2, 4, 6, or 24 hr after the end of 3 weeks' exposure. After 3 weeks of exposure the concentration of total white...... spirit was 1.5 and 5.6 mg/kg in blood; 7.1 and 17.1 mg/kg in brain; 432 and 1452 mg/kg in fat tissue at the exposure levels of 400 and 800 p.p.m., respectively. The concentrations of n-nonane, n-decane, n-undecane, and total white spirit in blood and brain were not affected by the duration of exposure...

Identification of Phosphoglycerate Kinase 1 (PGK1 as a reference gene for quantitative gene expression measurements in human blood RNA

Directory of Open Access Journals (Sweden)

Unger Elizabeth R

2011-09-01

Full Text Available Abstract Background Blood is a convenient sample and increasingly used for quantitative gene expression measurements with a variety of diseases including chronic fatigue syndrome (CFS. Quantitative gene expression measurements require normalization of target genes to reference genes that are stable and independent from variables being tested in the experiment. Because there are no genes that are useful for all situations, reference gene selection is an essential step to any quantitative reverse transcription-PCR protocol. Many publications have described appropriate genes for a wide variety of tissues and experimental conditions, however, reference genes that may be suitable for the analysis of CFS, or human blood RNA derived from whole blood as well as isolated peripheral blood mononuclear cells (PBMCs, have not been described. Findings Literature review and analyses of our unpublished microarray data were used to narrow down the pool of candidate reference genes to six. We assayed whole blood RNA from Tempus tubes and cell preparation tube (CPT-collected PBMC RNA from 46 subjects, and used the geNorm and NormFinder algorithms to select the most stable reference genes. Phosphoglycerate kinase 1 (PGK1 was one of the optimal normalization genes for both whole blood and PBMC RNA, however, additional genes differed for the two sample types; Ribosomal protein large, P0 (RPLP0 for PBMC RNA and Peptidylprolyl isomerase B (PPIB for whole blood RNA. We also show that the use of a single reference gene is sufficient for normalization when the most stable candidates are used. Conclusions We have identified PGK1 as a stable reference gene for use with whole blood RNA and RNA derived from PBMC. When stable genes are selected it is possible to use a single gene for normalization rather than two or three. Optimal normalization will improve the ability of results from PBMC RNA to be compared with those from whole blood RNA and potentially allows comparison of

Arsenic exposure from drinking water is associated with decreased gene expression and increased DNA methylation in peripheral blood

Energy Technology Data Exchange (ETDEWEB)

Ameer, Syeda Shegufta [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Engström, Karin [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden); Hossain, Mohammad Bakhtiar [Department of Laboratory Medicine, Division of Occupational and Environmental Medicine, Lund University, Lund (Sweden); Concha, Gabriela [Science Department, Risk Benefit Assessment Unit, National Food Agency, Uppsala (Sweden); Vahter, Marie [Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden); Broberg, Karin, E-mail: Karin.broberg@ki.se [Institute of Environmental Medicine, Unit of Metals & Health, Karolinska Institutet, Stockholm (Sweden)

2017-04-15

Background: Exposure to inorganic arsenic increases the risk of cancer and non-malignant diseases. Inefficient arsenic metabolism is a marker for susceptibility to arsenic toxicity. Arsenic may alter gene expression, possibly by altering DNA methylation. Objectives: To elucidate the associations between arsenic exposure, gene expression, and DNA methylation in peripheral blood, and the modifying effects of arsenic metabolism. Methods: The study participants, women from the Andes, Argentina, were exposed to arsenic via drinking water. Arsenic exposure was assessed as the sum of arsenic metabolites in urine (U-As), using high performance liquid-chromatography hydride-generation inductively-coupled-plasma-mass-spectrometry, and arsenic metabolism efficiency was assessed by the urinary fractions (%) of the individual metabolites. Genome-wide gene expression (N = 80 women) and DNA methylation (N = 93; 80 overlapping with gene expression) in peripheral blood were measured using Illumina DirectHyb HumanHT-12 v4.0 and Infinium Human-Methylation 450K BeadChip, respectively. Results: U-As concentrations, ranging 10–1251 μg/L, was associated with decreased gene expression: 64% of the top 1000 differentially expressed genes were down-regulated with increasing U-As. U-As was also associated with hypermethylation: 87% of the top 1000 CpGs were hypermethylated with increasing U-As. The expression of six genes and six individual CpG sites were significantly associated with increased U-As concentration. Pathway analyses revealed enrichment of genes related to cell death and cancer. The pathways differed somewhat depending on arsenic metabolism efficiency. We found no overlap between arsenic-related gene expression and DNA methylation for individual genes. Conclusions: Increased arsenic exposure was associated with lower gene expression and hypermethylation in peripheral blood, but with no evident overlap. - Highlights: • Women exposed to inorganic arsenic were studied for

Mannan-Modified PLGA Nanoparticles for Targeted Gene Delivery

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Fansheng Kong

2012-01-01

Full Text Available The studies of targeted gene delivery nanocarriers have gained increasing attention during the past decades. In this study, mannan modified DNA loaded bioadhesive PLGA nanoparticles (MAN-DNA-NPs were investigated for targeted gene delivery to the Kupffer cells (KCs. Bioadhesive PLGA nanoparticles were prepared and subsequently bound with pEGFP. Following the coupling of the mannan-based PE-grafted ligands (MAN-PE with the DNA-NPs, the MAN-DNA-NPs were delivered intravenously to rats. The transfection efficiency was determined from the isolated KCs and flow cytometry was applied for the quantitation of gene expression after 48 h post transfection. The size of the MAN-DNA-NPs was found to be around 190 nm and the Zeta potential was determined to be −15.46mV. The pEGFP binding capacity of MAN-DNA-NPs was (88.9±5.8% and the in vitro release profiles of the MAN-DNA-NPs follow the Higuchi model. When compared with non-modified DNA-NPs and Lipofectamine 2000-DNA, MAN-DNA-NPs produced the highest gene expressions, especially in vivo. The in vivo data from flow cytometry analysis showed that MAN-DNA-NPs displayed a remarkably higher transfection efficiency (39% than non-modified DNA-NPs (25% and Lipofectamine 2000-DNA (23% in KCs. The results illustrate that MAN-DNA-NPs have the ability to target liver KCs and could function as promising active targeting drug delivery vectors.

Large-Scale Candidate Gene Analysis in Whites and African Americans Identifies IL6R Polymorphism in Relation to Atrial Fibrillation The National Heart, Lung, and Blood Institute's Candidate Gene Association Resource (CARe) Project

NARCIS (Netherlands)

Schnabel, Renate B.; Kerr, Kathleen F.; Lubitz, Steven A.; Alkylbekova, Ermeg L.; Marcus, Gregory M.; Sinner, Moritz F.; Magnani, Jared W.; Wolf, Philip A.; Deo, Rajat; Lloyd-Jones, Donald M.; Lunetta, Kathryn L.; Mehra, Reena; Levy, Daniel; Fox, Ervin R.; Arking, Dan E.; Mosley, Thomas H.; Mueller-Nurasyid, Martina; Young, Taylor R.; Wichmann, H. -Erich; Seshadri, Sudha; Farlow, Deborah N.; Rotter, Jerome I.; Soliman, Elsayed Z.; Glazer, Nicole L.; Wilson, James G.; Breteler, Monique M. B.; Sotoodehnia, Nona; Newton-Cheh, Christopher; Kaeaeb, Stefan; Ellinor, Patrick T.; Alonso, Alvaro; Benjamin, Emelia J.; Heckbert, Susan R.

2011-01-01

Background-The genetic background of atrial fibrillation (AF) in whites and African Americans is largely unknown. Genes in cardiovascular pathways have not been systematically investigated. Methods and Results-We examined a panel of approximately 50 000 common single-nucleotide polymorphisms (SNPs)

Identification and validation of suitable endogenous reference genes for gene expression studies in human peripheral blood

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Turner Renee J

2009-08-01

Full Text Available Abstract Background Gene expression studies require appropriate normalization methods. One such method uses stably expressed reference genes. Since suitable reference genes appear to be unique for each tissue, we have identified an optimal set of the most stably expressed genes in human blood that can be used for normalization. Methods Whole-genome Affymetrix Human 2.0 Plus arrays were examined from 526 samples of males and females ages 2 to 78, including control subjects and patients with Tourette syndrome, stroke, migraine, muscular dystrophy, and autism. The top 100 most stably expressed genes with a broad range of expression levels were identified. To validate the best candidate genes, we performed quantitative RT-PCR on a subset of 10 genes (TRAP1, DECR1, FPGS, FARP1, MAPRE2, PEX16, GINS2, CRY2, CSNK1G2 and A4GALT, 4 commonly employed reference genes (GAPDH, ACTB, B2M and HMBS and PPIB, previously reported to be stably expressed in blood. Expression stability and ranking analysis were performed using GeNorm and NormFinder algorithms. Results Reference genes were ranked based on their expression stability and the minimum number of genes needed for nomalization as calculated using GeNorm showed that the fewest, most stably expressed genes needed for acurate normalization in RNA expression studies of human whole blood is a combination of TRAP1, FPGS, DECR1 and PPIB. We confirmed the ranking of the best candidate control genes by using an alternative algorithm (NormFinder. Conclusion The reference genes identified in this study are stably expressed in whole blood of humans of both genders with multiple disease conditions and ages 2 to 78. Importantly, they also have different functions within cells and thus should be expressed independently of each other. These genes should be useful as normalization genes for microarray and RT-PCR whole blood studies of human physiology, metabolism and disease.

White blood cell counts and neutrophil to lymphocyte ratio in the diagnosis of testicular cancer: a simple secondary serum tumor marker.

Science.gov (United States)

Yuksel, Ozgur Haki; Verit, Ayhan; Sahin, Aytac; Urkmez, Ahmet; Uruc, Fatih

2016-01-01

The aim of the study was to investigate white blood cell counts and neutrophil to lymphocyte ratio (NLR) as markers of systemic inflammation in the diagnosis of localized testicular cancer as a malignancy with initially low volume. Thirty-six patients with localized testicular cancer with a mean age of 34.22±14.89 years and 36 healthy controls with a mean age of 26.67±2.89 years were enrolled in the study. White blood cell counts and NLR were calculated from complete blood cell counts. White blood cell counts and NLR were statistically significantly higher in patients with testicular cancer compared with the control group (ptesticular cancer besides the well-known accurate serum tumor markers as AFP (alpha fetoprotein), hCG (human chorionic gonadotropin) and LDH (lactate dehydrogenase).

Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.

Science.gov (United States)

Ojima, Toshiyasu; Iwahashi, Makoto; Nakamura, Masaki; Matsuda, Kenji; Nakamori, Mikihito; Ueda, Kentaro; Naka, Teiji; Katsuda, Masahiro; Miyazawa, Motoki; Yamaue, Hiroki

2007-10-01

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.

The effect of various antibiotics on the labelling efficiency of human white blood cells with 111In-oxine

International Nuclear Information System (INIS)

Sinzinger, Helmut; Granegger, Susanne

1988-01-01

Earlier clinical studies revealed that in patients suffering from chronic osteomyelitis undergoing antibiotic therapy the white blood cell scanning missed the right diagnosis in 40% of cases, whereas all the acute untreated cases were imaged correctly. Thus, it was suspected that an impaired labelling efficiency and white blood cell function might have been causative. Retrospective analysis of labelling efficiency exhibited no difference between patients on antibiotics and those not on antibiotics. Prospective cellular viability testing in 81 patients, 71 of whom were on various antibiotics, using latex particles (phagocytosis) and the Trypan blue exclusion test, did not reveal any different function behaviour either. Examining the labelling efficiency (after 111 In-oxine and 111 In-oxine-sulphate labelling), recovery, half-life and viability of white blood cells of 107 patients undergoing therapy with various antibiotics as compared to controls, it becomes evident that the antibiotic therapy is not causative of the clinical difference observed. (author)

Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies.

Science.gov (United States)

Yarnell, J W; Baker, I A; Sweetnam, P M; Bainton, D; O'Brien, J R; Whitehead, P J; Elwood, P C

1991-03-01

Recent studies have suggested that hemostatic factors and white blood cell count are predictive of ischemic heart disease (IHD). The relations of fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. The two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count. Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count. Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both. Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors. Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index. Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD.

Actin genes and their expression in pacific white shrimp, Litopenaeus vannamei.

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Zhang, Xiaoxi; Zhang, Xiaojun; Yuan, Jianbo; Du, Jiangli; Li, Fuhua; Xiang, Jianhai

2018-04-01

Actin is a multi-functional gene family that can be divided into muscle-type actins and non-muscle-type actins. In this study, 37 unigenes encoding actins were identified from RNA-Seq data of Pacific white shrimp, Litopenaeus vannamei. According to phylogenetic analysis, four and three cDNAs belong to cytoplasmic- and heart-type actins and were named LvActinCT and LvActinHT, respectively. 10 cDNAs belong to the slow-type skeletal muscle actins, and 18 belong to the fast-type skeletal muscle actins; they were designated LvActinSSK and LvActinFSK, respectively. Some muscle actin genes formed gene clusters in the genome. Multiple alternative transcription starts sites (ATSSs) were found for LvActinCT1. Based on the early developmental expression profile, almost all LvActins were highly expressed between the early limb bud and post-larval stages. Using LvActinSSK5 as probes, slow-type muscle was localized in pleopod muscle and superficial ventral muscle. We also found three actin genes that were down-regulated in the hemocytes of white spot syndrome virus (WSSV)- and Vibrio parahaemolyticus-infected L. vannamei. This study provides valuable information on the actin gene structure of shrimp, furthers our understanding of the shrimp muscle system and helps us develop strategies for disease control and sustainable shrimp farming.

Blood Gene Expression Predicts Bronchiolitis Obliterans Syndrome

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Richard Danger

2018-01-01

Full Text Available Bronchiolitis obliterans syndrome (BOS, the main manifestation of chronic lung allograft dysfunction, leads to poor long-term survival after lung transplantation. Identifying predictors of BOS is essential to prevent the progression of dysfunction before irreversible damage occurs. By using a large set of 107 samples from lung recipients, we performed microarray gene expression profiling of whole blood to identify early biomarkers of BOS, including samples from 49 patients with stable function for at least 3 years, 32 samples collected at least 6 months before BOS diagnosis (prediction group, and 26 samples at or after BOS diagnosis (diagnosis group. An independent set from 25 lung recipients was used for validation by quantitative PCR (13 stables, 11 in the prediction group, and 8 in the diagnosis group. We identified 50 transcripts differentially expressed between stable and BOS recipients. Three genes, namely POU class 2 associating factor 1 (POU2AF1, T-cell leukemia/lymphoma protein 1A (TCL1A, and B cell lymphocyte kinase, were validated as predictive biomarkers of BOS more than 6 months before diagnosis, with areas under the curve of 0.83, 0.77, and 0.78 respectively. These genes allow stratification based on BOS risk (log-rank test p < 0.01 and are not associated with time posttransplantation. This is the first published large-scale gene expression analysis of blood after lung transplantation. The three-gene blood signature could provide clinicians with new tools to improve follow-up and adapt treatment of patients likely to develop BOS.

Investigation of nanodiamonds interactions in canine blood

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WÄ sowicz, Michał; Marek, Kulka; Cićkiewicz, Maciej; Cymerman, Magdalena

2017-02-01

The whole blood contains red cells, white cells, and platelets suspended in plasma. In the following study we investigated an impact of nanodiamond particles on blood elements over various periods of time.The material used in the study consisted of samples taken from ten healthy canines (Canis lupus f. domestica) of various age, different blood types and both sexes. The markings were conducted by adding to the blood unmodified diamonds (SND), modified O2 (SO2) suspended in 0,9% NaCl. The blood was put under an impact of two diamond concentrations: 20μl and 100μl. The amount of abnormal cells increased with time. The percentage of echinocytes as a result of interaction with nanodiamonds in various time periods for individual specimens was scarce. In the examined microscopic image a summary was made for 100 white blood cells. Following cells were included in said group: band neutrophils, segmented neutrophils, eosinophils, basophils, lymphocytes, monocytes, lymphocytes with granulates, stimulated lymphocytes, lymphocytes with vacuoles, metamielocytes and smudge cells. The impact of the three diamond types had no clinical importance on red blood cells. After the diamonds mixed with white blood cells, atypical cells came into being, in the range of agranulocytes in stimulated form or with granulates and/or vacuoles. It is supposed that as a result of longlasting exposure a stimulation and vacuolisation takes place, because of the function of the cells.

Ambulatory monitoring of blood pressure and pregnancy outcome in pregnant women with white coat hypertension in the third trimester of pregnancy.

Science.gov (United States)

Shahbazian, Nahid; Shahbazian, Heshmatollah; Mohammadjafari, Razieh; Mousavi, Mahsan

2013-01-01

Introduction: If the blood pressure of a pregnant woman is ≥140/90 mmHg at the clinic, but her ambulatory blood pressure is less coat hypertension. Objectives: To evaluate the value of ambulatory blood pressure monitoring in pregnant women. Patients and Methods: This prospective cohort study was conducted in Imam-Khomeini hospital of Ahwaz, Iran between 2011 to 2012. A total of 105 pregnant women who had blood pressure of higher than 140/90 mmHg during the third trimester of pregnancy were monitored. Thirty five women with white coat hypertension, 35 women with gestational hypertension and 35 women with normal blood pressure were followed. The data were analyzed using the Kolmogorov-Smirnov test, Pearson correlation coefficient and Chi-square tests. Results: The prevalence of white coat hypertension was 31.3%. The maternal and neonatal outcomes and laboratory examinations in white coat hypertension were similar to the normal blood pressure, but the frequency of caesarean section was more than the other two groups. Conclusion: The findings of the study indicate the efficacy of 24 hour holter monitoring of blood pressure and using it more comprehensively , compared to the limited visits.

De Novo Assembly of the Donkey White Blood Cell Transcriptome and a Comparative Analysis of Phenotype-Associated Genes between Donkeys and Horses.

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Feng-Yun Xie

Full Text Available Prior to the mechanization of agriculture and labor-intensive tasks, humans used donkeys (Equus africanus asinus for farm work and packing. However, as mechanization increased, donkeys have been increasingly raised for meat, milk, and fur in China. To maintain the development of the donkey industry, breeding programs should focus on traits related to these new uses. Compared to conventional marker-assisted breeding plans, genome- and transcriptome-based selection methods are more efficient and effective. To analyze the coding genes of the donkey genome, we assembled the transcriptome of donkey white blood cells de novo. Using transcriptomic deep-sequencing data, we identified 264,714 distinct donkey unigenes and predicted 38,949 protein fragments. We annotated the donkey unigenes by BLAST searches against the non-redundant (NR protein database. We also compared the donkey protein sequences with those of the horse (E. caballus and wild horse (E. przewalskii, and linked the donkey protein fragments with mammalian phenotypes. As the outer ear size of donkeys and horses are obviously different, we compared the outer ear size-associated proteins in donkeys and horses. We identified three ear size-associated proteins, HIC1, PRKRA, and KMT2A, with sequence differences among the donkey, horse, and wild horse loci. Since the donkey genome sequence has not been released, the de novo assembled donkey transcriptome is helpful for preliminary investigations of donkey cultivars and for genetic improvement.

Blood Gene Expression Profiling of Breast Cancer Survivors Experiencing Fibrosis

International Nuclear Information System (INIS)

Landmark-Hoyvik, Hege; Dumeaux, Vanessa; Reinertsen, Kristin V.; Edvardsen, Hege; Fossa, Sophie D.; Borresen-Dale, Anne-Lise

2011-01-01

Purpose: To extend knowledge on the mechanisms and pathways involved in maintenance of radiation-induced fibrosis (RIF) by performing gene expression profiling of whole blood from breast cancer (BC) survivors with and without fibrosis 3-7 years after end of radiotherapy treatment. Methods and Materials: Gene expression profiles from blood were obtained for 254 BC survivors derived from a cohort of survivors, treated with adjuvant radiotherapy for breast cancer 3-7 years earlier. Analyses of transcriptional differences in blood gene expression between BC survivors with fibrosis (n = 31) and BC survivors without fibrosis (n = 223) were performed using R version 2.8.0 and tools from the Bioconductor project. Gene sets extracted through a literature search on fibrosis and breast cancer were subsequently used in gene set enrichment analysis. Results: Substantial differences in blood gene expression between BC survivors with and without fibrosis were observed, and 87 differentially expressed genes were identified through linear analysis. Transforming growth factor-β1 signaling was identified as the most significant gene set, showing a down-regulation of most of the core genes, together with up-regulation of a transcriptional activator of the inhibitor of fibrinolysis, Plasminogen activator inhibitor 1 in the BC survivors with fibrosis. Conclusion: Transforming growth factor-β1 signaling was found down-regulated during the maintenance phase of fibrosis as opposed to the up-regulation reported during the early, initiating phase of fibrosis. Hence, once the fibrotic tissue has developed, the maintenance phase might rather involve a deregulation of fibrinolysis and altered degradation of extracellular matrix components.

White blood cell-based detection of asymptomatic scrapie infection by ex vivo assays.

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Sophie Halliez

Full Text Available Prion transmission can occur by blood transfusion in human variant Creutzfeldt-Jakob disease and in experimental animal models, including sheep. Screening of blood and its derivatives for the presence of prions became therefore a major public health issue. As infectious titer in blood is reportedly low, highly sensitive and robust methods are required to detect prions in blood and blood derived products. The objectives of this study were to compare different methods--in vitro, ex vivo and in vivo assays--to detect prion infectivity in cells prepared from blood samples obtained from scrapie infected sheep at different time points of the disease. Protein misfolding cyclic amplification (PMCA and bioassays in transgenic mice expressing the ovine prion protein were the most efficient methods to identify infected animals at any time of the disease (asymptomatic to terminally-ill stages. However scrapie cell and cerebellar organotypic slice culture assays designed to replicate ovine prions in culture also allowed detection of prion infectivity in blood cells from asymptomatic sheep. These findings confirm that white blood cells are appropriate targets for preclinical detection and introduce ex vivo tools to detect blood infectivity during the asymptomatic stage of the disease.

White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

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Jin Woo Choi

Full Text Available The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN. A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of

White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

Science.gov (United States)

Choi, Jin Woo; Ku, Yunseo; Yoo, Byeong Wook; Kim, Jung-Ah; Lee, Dong Soon; Chai, Young Jun; Kong, Hyoun-Joong; Kim, Hee Chan

2017-01-01

The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method

White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks

Science.gov (United States)

Choi, Jin Woo; Ku, Yunseo; Yoo, Byeong Wook; Kim, Jung-Ah; Lee, Dong Soon; Chai, Young Jun; Kong, Hyoun-Joong

2017-01-01

The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method

Research on effects of ionizing radiation of human peripheral blood white cell adhesive molecules

International Nuclear Information System (INIS)

Li Haijun; Cheng Ying; Le Chen; Min Rui

2008-01-01

Objective: To investigate the links between expression and function of adhesive molecule on the surface of irradiated peripheral blood white cells. Methods: Heparinized human peripheral blood was exposed to γ rays with different dose. At the different post-radiation time adhesive molecule expression on cellular surface was determined by double fluorescence labeling antibodies which were against adhesive molecule and special mark of granulocyte or mononuclear cell respectively with flow cytometry, and cellular adhesive ability to different matrixes mediated by adhesive molecule was estimated by commercializing enzyme-linked immunosorbent assay kit and crystalviolet dying. Results: A decline pattern of CD11b on surface of mononuclear cells and CD29 on surface of granulocyte with irradiation dose increase was found. The changes of adhesive ability of mononuclear cells to substance of β1-integrin and collagen-I was well related with irradiation dose. Conclusion: Good relationship shown by the changes of adhesive molecule expression and adhesive ability mediated by the molecules on the surface of peripheral blood white cells with radiation dose was primary base of further research on indicting exposure dose by biomarker. (authors)

White coat hypertension in pediatrics.

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Jurko, Alexander; Minarik, Milan; Jurko, Tomas; Tonhajzerova, Ingrid

2016-01-15

The article summarizes current information on blood pressure changes in children during clinic visit. White coat as a general dressing of physicians and health care personnel has been widely accepted at the end of the 19th century. Two problems can be associated with the use of white coat: white coat phenomenon and white coat hypertension. Children often attribute pain and other unpleasant experience to the white coat and refuse afterwards cooperation with examinations. Definition of white coat hypertension in the literature is not uniform. It has been defined as elevated blood pressure in the hospital or clinic with normal blood pressure at home measured during the day by ambulatory blood pressure monitoring system. White coat effect is defined as temporary increase in blood pressure before and during visit in the clinic, regardless what the average daily ambulatory blood pressure values are. Clinical importance of white coat hypertension is mainly because of higher risk for cardiovascular accidents that are dependent on end organ damage (heart, vessels, kidney). Current data do not allow any clear recommendations for the treatment. Pharmacological therapy is usually started in the presence of hypertrophic left ventricle, changes in intimal/medial wall thickness of carotic arteries, microalbuminuria and other cardiovascular risk factors. Nonpharmacological therapy is less controversial and certainly more appropriate. Patients have to change their life style, need to eliminate as much cardiovascular risk factors as possible and sustain a regular blood pressure monitoring.

Biomarkers in white-coat hypertension

OpenAIRE

Martin, Catherine Ann

2017-01-01

The introduction of ambulatory blood pressure monitoring in the 1960s provided new insights into the nature of high blood pressure disorders. Blood pressure is now categorised into four quadrants:normotension, masked hypertension, hypertension and white-coat hypertension. In white-coat hypertension blood pressure is elevated when taken at the doctor’s office but normal if taken outside the doctor’s office. Several controversies are associated with white-coat hypertension, which are discuss...

Protein O-GlcNAc Modification Increases in White Blood Cells After a Single Bout of Physical Exercise.

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Nagy, Tamás; Kátai, Emese; Fisi, Viktória; Takács, Tamás Tibor; Stréda, Antal; Wittmann, István; Miseta, Attila

2018-01-01

Protein O-linked N -acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification influencing the function of many intracellular proteins. Recently it was revealed that O-GlcNAc regulation is modified under various stress states, including ischemia and oxidative stress. Aside from a few contradictory studies based on animal models, the effect of exercise on O-GlcNAc is unexplored. To evaluate O-GlcNAc levels in white blood cells (WBC) of human volunteers following physical exercise. Young (age 30 ± 5.2), healthy male volunteers ( n  = 6) were enlisted for the study. Blood parameters including metabolites, ions, "necro"-enzymes, and cell counts were measured before and after a single bout of exercise (2-mile run). From WBC samples, we performed western blots to detect O-GlcNAc modified proteins. The distribution of O-GlcNAc in WBC subpopulations was assessed by flow cytometry. Elevation of serum lactic acid (increased from 1.3 ± 0.4 to 6.9 ± 1.7 mM), creatinine (from 77.5 ± 6.3 U/L to 102.2 ± 7.0 μM), and lactate dehydrogenase (from 318.5 ± 26.2 to 380.5 ± 33.2 U/L) confirmed the effect of exercise. WBC count also significantly increased (from 6.6 ± 1.0 to 8.4 ± 1.4 G/L). The level of O-GlcNAc modified proteins in WBCs showed significant elevation after exercise (85 ± 51%, p  O-GlcNAc status of WBCs. O-GlcNAc modification could be a natural process by which physical activity modulates the immune system. Further research could elucidate the role of O-GlcNAc during exercise and validate O-GlcNAc as a biomarker for fitness assessment.

Differential associations between white blood cell counts and fatigue in young and older adults

DEFF Research Database (Denmark)

Avlund, Kirsten; Hokland, Marianne; Mehlsen, Mimi Yung

2012-01-01

The aims of this exploratory study were to study whether fatigue might be related to the cellular immune system by 1) analysing if the number of white blood cell subsets are related to fatigue and 2) if possible relationships vary in younger and older community-dwelling individuals....

White blood cell and platelet count as adjuncts to standard clinical evaluation for risk assessment in patients at low probability of acute aortic syndrome.

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Morello, Fulvio; Cavalot, Giulia; Giachino, Francesca; Tizzani, Maria; Nazerian, Peiman; Carbone, Federica; Pivetta, Emanuele; Mengozzi, Giulio; Moiraghi, Corrado; Lupia, Enrico

2017-08-01

Pre-test probability assessment is key in the approach to suspected acute aortic syndromes (AASs). However, most patients with AAS-compatible symptoms are classified at low probability, warranting further evaluation for decision on aortic imaging. White blood cell count, platelet count and fibrinogen explore pathophysiological pathways mobilized in AASs and are routinely assayed in the workup of AASs. However, the diagnostic performance of these variables for AASs, alone and as a bundle, is unknown. We tested the hypothesis that white blood cell count, platelet count and/or fibrinogen at presentation may be applied as additional tools to standard clinical evaluation for pre-test risk assessment in patients at low probability of AAS. This was a retrospective observational study conducted on consecutive patients managed in our Emergency Department from 2009 to 2014 for suspected AAS. White blood cell count, platelet count and fibrinogen were assayed during evaluation in the Emergency Department. The final diagnosis was obtained by computed tomography angiography. The pre-test probability of AAS was defined according to guidelines. Of 1210 patients with suspected AAS, 1006 (83.1%) were classified at low probability, and 271 (22.4%) were diagnosed with AAS. Within patients at low probability, presence of at least one alteration among white blood cell count >9*10 3 /µl, platelet count probability, white blood cell count >9*10 3 /µl and platelet count probability, the estimated risk of AAS based on the number of alterations amongst white blood cell count >9*10 3 /µl and platelet count probability to fine-tune risk assessment of AAS.

Inter-arm blood pressure differences compared with ambulatory monitoring: a manifestation of the 'white-coat' effect?

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Martin, Una; Holder, Roger; Hodgkinson, James; McManus, Richard

2013-02-01

Inter-arm difference in blood pressure of >10 mmHg is associated with peripheral vascular disease, but it is unclear how much of the difference in sequential right and left arm blood pressure measurements might be due to a 'white-coat' effect. To use ambulatory blood pressure monitoring (ABPM) to better understand the clinical significance of inter-arm differences in blood pressure. Retrospective study in a teaching hospital in Birmingham. Anonymised clinical data collected from 784 patients attending a single hospital-based hypertension clinic were retrospectively analysed. Each participant had blood pressure measured sequentially in both arms, followed by ABPM over the subsequent 24 hours. Data were available for 710 (91%) patients, of whom 39.3% (279) had a blood pressure difference of 10 mmHg or more between each arm. Compared to daytime systolic ABPM, the difference was 25.1 mmHg using the arm with the highest reading, but only 15.5 mmHg if the lower reading was taken (mean difference 9.6 mmHg (95% confidence interval [CI] = 9.0 mmHg to 10.3 mmHg)). However, differences between mean right (20.7 mmHg) or left (19.9 mmHg) arm blood pressure and daytime systolic ABPM were very similar. Compared with ABPM, use of the higher of the left and right arm readings measured sequentially appears to overestimate true mean blood pressure. As there is no significant difference in the extent of disparity with ABPM by left or right arm, this is unlikely to be due to arm dominance and may be due to the 'white-coat' effect reducing blood pressure on repeated measurement. Where a large inter-arm blood pressure difference is detected with sequential measurement, healthcare professionals should re-measure the blood pressure in the original arm.

Strategies used for genetically modifying bacterial genome: ite-directed mutagenesis, gene inactivation, and gene over-expression*

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Xu, Jian-zhong; Zhang, Wei-guo

2016-01-01

With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators. PMID:26834010

A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity- and Cancer-Related Genes in Whole Blood of Humans.

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Charron, Craig S; Dawson, Harry D; Albaugh, George P; Solverson, Patrick M; Vinyard, Bryan T; Solano-Aguilar, Gloria I; Molokin, Aleksey; Novotny, Janet A

2015-11-01

Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease. We designed a study to probe the mechanisms of garlic action in humans. We conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15 g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was collected before and 3 h after test meal consumption for gene expression analysis in whole blood. Illumina BeadArray was used to screen for genes of interest, followed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6 cells were treated with a purified garlic extract (0.5 μL/mL), and mRNA was measured by qRT-PCR at 0, 3, 6, and 24 h. The following 7 genes were found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1α (HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1), oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog (REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1) (P garlic, respectively). OSM is a pleiotropic cytokine that inhibits several tumor cell lines in culture. These data indicate that the bioactivity of garlic is multifaceted and includes activation of genes related to immunity, apoptosis, and xenobiotic metabolism in humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as NCT01293591. © 2015 American Society for Nutrition.

Ultrasonography and indium 111 white blood cell scanning for the detection of intraabdominal abscesses

International Nuclear Information System (INIS)

Carroll, B.; Silverman, P.M.; Goodwin, D.A.; McDougall, I.R.

1981-01-01

Ultrasound and indium 111 white blood cell scanning were performed on 163 patients with suspected intraabdominal abscesses. In all but one case, intraabdominal abscesses were correctly identified by one or both tests; conversely, no patient was falsely diagnosed by both tests to have an abscess. Sonography was useful in those patients with focal symptoms, and frequently identified nonabscess causes for fever. White cell scanning was valuable when focal signs were absent, and frequently identified extraabdominal sources of sepsis. The two imaging modalities are complementary and provide a highly accurate and sensitive means of intraabdominal abscess detection

Mimicking the Interfacial Dynamics of Flowing White Blood Cells

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Santore, Maria

2015-03-01

The rolling of particles on surfaces, facilitated by hydrodynamic forces combined with localized surface interactions of the appropriate strengths, spatial arrangements, and ranges, is a technologically useful means of transporting and manipulating particles. One's intuition for the rolling of a marble or a car tire cannot be extrapolated down to microparticle length scales because the microparticle interactions are dominated by electrostatic, van der Waals, and hydrogen bonding interactions rather than a friction that depends on an imposed normal force. Indeed, our microparticle rolling systems are inspired by the rolling of white blood cells on the inner walls of venules as part of the innate immune response: Selectin molecules engage with their counterparts on the opposing surfaces to slow cell motion relative to that for freely flowing cells. In the resulting rolling signature, ligand-receptor binding and crack closing on the front of the cell are balanced with molecular dis-bonding and crack opening at the rear. The contact region is relatively static, allowing other interactions (for instance signaling) to occur for a finite duration. Thus, achieving particle rolling in synthetic systems is important because it facilitates particle-surface interactions in a continuous nonfouling fashion where the contact surface is continually renewed. In developing a synthetic model for this system, we employ polymers to modify flowing particles and /or planar collectors, producing heterogeneous interfaces which can support rolling or produce other motion signatures such as skipping, arrest, or free flow. We identify, in the synthetic system, combinations of variables that produce rolling and demonstrate how the distinction between rolling and arrest is not a simple matter of the adhesion strength between the particles and the collector. Rolling is a cooperative process and the coordination of binding in one location with dis-bonding in another requires appropriate length

RNA-seq analyses of blood-induced changes in gene expression in the mosquito vector species, Aedes aegypti

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Olson Ken E

2011-01-01

Full Text Available Abstract Background Hematophagy is a common trait of insect vectors of disease. Extensive genome-wide transcriptional changes occur in mosquitoes after blood meals, and these are related to digestive and reproductive processes, among others. Studies of these changes are expected to reveal molecular targets for novel vector control and pathogen transmission-blocking strategies. The mosquito Aedes aegypti (Diptera, Culicidae, a vector of Dengue viruses, Yellow Fever Virus (YFV and Chikungunya virus (CV, is the subject of this study to look at genome-wide changes in gene expression following a blood meal. Results Transcriptional changes that follow a blood meal in Ae. aegypti females were explored using RNA-seq technology. Over 30% of more than 18,000 investigated transcripts accumulate differentially in mosquitoes at five hours after a blood meal when compared to those fed only on sugar. Forty transcripts accumulate only in blood-fed mosquitoes. The list of regulated transcripts correlates with an enhancement of digestive activity and a suppression of environmental stimuli perception and innate immunity. The alignment of more than 65 million high-quality short reads to the Ae. aegypti reference genome permitted the refinement of the current annotation of transcript boundaries, as well as the discovery of novel transcripts, exons and splicing variants. Cis-regulatory elements (CRE and cis-regulatory modules (CRM enriched significantly at the 5'end flanking sequences of blood meal-regulated genes were identified. Conclusions This study provides the first global view of the changes in transcript accumulation elicited by a blood meal in Ae. aegypti females. This information permitted the identification of classes of potentially co-regulated genes and a description of biochemical and physiological events that occur immediately after blood feeding. The data presented here serve as a basis for novel vector control and pathogen transmission

Lignin-modifying enzymes of the white rot basidiomycete Ganoderma lucidum

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D/Souza, T.M.; Merritt, C.S.; Reddy, C.A.

1999-12-01

Ganoderma lucidum, a white rot basidiomycete widely distributed worldwide, was studied for the production of the lignin-modifying enzymes laccase, manganese-dependent peroxidase (MnP), and lignin peroxidase (LiP). Laccase levels observed in high-nitrogen shaken cultures were much greater than those seen in low-nitrogen, malt extract, or wool-grown cultures and those reported for most other white rot fungi to date. Laccase production was readily seen in cultures grown with pine or poplar as the sole carbon and energy source. Cultures containing both pine and poplar showed 5- to 10-fold-higher levels of laccase than cultures containing pine or poplar alone. Since syringyl units are structural components important in poplar lignin and other hardwoods but much less so in pine lignin and other softwoods, pine cultures were supplemented with syringic acid, and this resulted in laccase levels comparable to those seen in pine-plus-poplar cultures. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of concentrated extracellular culture fluid from HM cultures showed two laccase activity bands, where as isoelectric focusing revealed five major laccase activity bands with estimated pIs of 3.0, 4.25, 4.5, and 5.1. Low levels of MnP activity were detected in poplar-grown cultures but not in cultures grown with pine, with pine plus syringic acid, or in HN medium. No LiP activity was seen in any of the media tested; however, probing the genomic DNA with the LiP cDNA (CLG4) from the white rot fungus Phanerochaete chrysosporium showed distinct hybridization bands suggesting the presence of lip-like sequences in G. lucidum.

Effects of Transport and Storage Conditions on Gene Expression in Blood Samples.

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Malentacchi, Francesca; Pizzamiglio, Sara; Wyrich, Ralf; Verderio, Paolo; Ciniselli, Chiara; Pazzagli, Mario; Gelmini, Stefania

2016-04-01

Inappropriate handling of blood samples might induce or repress gene expression and/or lead to RNA degradation affecting downstream analysis. In particular, sample transport is a critical step for biobanking or multicenter studies because of uncontrolled variables (i.e., unstable temperature). We report the results of a pilot study implemented within the EC funded SPIDIA project, aimed to investigate the role of transport and storage of blood samples containing and not containing an RNA stabilizer. Blood was collected from a single donor both in EDTA and in PAXgene Blood RNA tubes. Half of the samples were sent to a second laboratory both at room temperature and at 4°C, whereas the remaining samples were stored at room temperature and at 4°C. Gene expression of selected genes (c-FOS, IL-1β, IL-8, and GAPDH) known to be induced or repressed by ex vivo blood handling and of blood-mRNA quality biomarkers identified and validated within the SPIDIA project, which allow for monitoring changes in unstabilized blood samples after collection and during transport and storage, were analyzed by RT-qPCR. If the shipment of blood in tubes not containing RNA stabilizer is not performed under a stable condition, gene profile studies can be affected by the effects of transport. Moreover, also controlled temperature shipment (4°C) can influence the expression of specific genes if blood is collected in tubes not containing a stabilizer. The use of dedicated biomarkers or time course experiments should be performed in order to verify potential bias on gene expression analysis due to sample shipment and storage conditions. Alternatively, the use of RNA stabilizer containing tubes can represent a reliable option to avoid ex vivo RNA changes.

Relationship of Hypertension, Blood Pressure, and Blood Pressure Control With White Matter Abnormalities in the Women’s Health Initiative Memory Study (WHIMS)—MRI Trial

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Kuller, Lewis H.; Margolis, Karen L.; Gaussoin, Sarah A.; Bryan, Nick R.; Kerwin, Diana; Limacher, Marian; Wassertheil-Smoller, Sylvia; Williamson, Jeff; Robinson, Jennifer G.

2010-01-01

This paper evaluates the relationship of blood pressure (BP) levels at Women’s Health Initiative (WHI) baseline, treatment of hypertension, and white matter abnormalities among women in conjugated equine estrogen (CEE) and medroxyprogesterone acetate and CEE-alone arms. The WHI Memory Study—Magnetic Resonance Imaging (WHIMS-MRI) trial scanned 1424 participants. BP levels at baseline were significantly positively related to abnormal white matter lesion (WML) volumes. Participants treated for h...

The investigation for potential modifier genes in patients with neurofibromatosis type 1 based on next-generation sequencing

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Yang F

2018-02-01

Full Text Available Fan Yang,1,2,* Song Xu,1,2,* Renwang Liu,1,2 Tao Shi,3 Xiongfei Li,1 Xuebing Li,2 Gang Chen,1 Hongyu Liu,2 Qinghua Zhou,1,2 Jun Chen1,2 1Department of Lung Cancer Surgery, 2Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, 3Department of Pathology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China *These authors contributed equally to this work Introduction: Neurofibromatosis type 1 (NF1 is a common Mendelian multi-system disorder that is characterized by café-au-lait spots (CLS, axillary freckling, optic glioma and plexiform neurofibroma. Various mutations of the NF1 gene are widely accepted to be the main cause of this disease, while whether there are still certain other modifier genes that could influence the phenotypes of NF1 is our concern. Patients and Methods: One proband and his father are involved, who are characterized by plexiform neurofibroma and cutaneous neurofibroma, respectively. Enhanced Computed tomography (CT and Positron emission tomography-CT (PET-CT were taken to collect the radiographic data, and the specimens of this neurofibroma as well as the blood samples from the father and son were sent for panel mutation screening of 295 tumor-related genes based on next-generation screening. Furthermore, the NF1 gene mutations were referred with Canis lupus familiaris, Rattus norvegicus, Gallus gallus, Danio rerio, and Drosophila melanogaster NF1 sequencing for evolutionary conservativeness and then analyzed in Condel databases for pathogenicity prediction. Results: The radiography indicated that the benign plexiform neurofibroma only occurred in the son. Also, TP53, FANCA, BCL6, PIK3C2G, RNF43, FGFR4, FLT3, ERBB2, PAK7, NSD1, MEN1 and TSC1 were uniquely found mutated in the son, which could be candidates as new modifier genes; besides, RNF43 was also mutated in public neurofibroma seuquencing data. By KEGG pathway annotation

Direct detection of the AR-E211 G > A gene polymorphism from blood and tissue samples without DNA isolation.

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Reptova, Silvie; Trtkova, Katerina Smesny; Kolar, Zdenek

2014-04-01

The pathogenesis of prostate cancer (CaP) involves alterations in a gene structure of the androgen receptor (AR). The single nucleotide polymorphism AR-E211 G > A localized in exon 1 of the AR gene (G1733A) was detected using direct polymerase chain reaction and restriction digestion (PCR-RFLP) method on blood and tissue samples without prior DNA isolation. We used blood samples of patients with a diagnosis of benign prostatic hyperplasia (BPH) or CaP. From monitored group of CaP patients were selected specimen in formalin-fixed paraffin-embedded tissue blocks with morphology of BPH and CaP. The main objective of our study was to develop a method based the direct PCR-RFLP analysis from blood and tissue without prior DNA isolation for faster genotyping analysis of a large number of samples. We found no statistically significant differences in allelic % of the AR-E211 G > A polymorphism between BPH and CaP patients (p ≤ 0.8462). Genotyping of the AR-E211 G > A variant in blood was not identical with tumor tissue genotyping analysis. Significant agreement between blood and tissue AR-E211 G > A polymorphism only in non-tumor tissue focus was confirmed. Although we analyzed a limited number of the tissue samples, we suppose that a presence of the minor allele A may be associated with cancer transformation-induced changes of the modified AR gene.

Tumor blood flow modifying effects of electrochemotherapy. A potential vascular targeted mechanism

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Sersa, G.; Cemazar, M.; Miklavcic, D.

2003-01-01

Background. The aim of this study was to determine the tumor blood flow modifying, and potential vascular targeted effect of electrochemotherapy with bleomycin or cisplatin. Materials and methods. Electrochemotherapy was performed by application of short intense electric pulses to the tumors after systemic administration of bleomycin or cisplatin. Evaluated were antitumor effectiveness of electrochemotherapy by tumor measurement, tumor blood flow modifying effect by Patent blue staining technique, and sensitivity of endothelial and tumor cells to the drugs and electrochemotherapy by clonogenicity assay. Results. Electrochemotherapy was effective in treatment of SA-1 tumors in A/J mice resulting in substantial tumor growth delay and also tumor cures. Tumor blood flow reduction following electrochemotherapy correlated well with its antitumor effectiveness. Virtually complete shut down of the tumor blood flow was observed already at 24 h after electrochemotherapy with bleomycin whereas only 50% reduction was observed after electrochemotherapy with cisplatin. Sensitivity of human endothelial HMEC-1 cells to electrochemotherapy suggests a vascular targeted effect for electrochemotherapy in vivo with bleomycin as well as with cisplatin. Conclusion. These results show that, in addition to direct electroporation of tumor cells, other vascular targeted mechanisms are involved in electrochemotherapy with bleomycin or cisplatin, potentially mediated by tumor blood flow reduction, and enhanced tumor cell death as a result of endothelial damage by electrochemotherapy. (author)

Development and Application of Loop-Mediated Isothermal Amplification Assays for Rapid Visual Detection of cry2Ab and cry3A Genes in Genetically-Modified Crops

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Feiwu Li

2014-08-01

Full Text Available The cry2Ab and cry3A genes are two of the most important insect-resistant exogenous genes and had been widely used in genetically-modified crops. To develop more effective alternatives for the quick identification of genetically-modified organisms (GMOs containing these genes, a rapid and visual loop-mediated isothermal amplification (LAMP method to detect the cry2Ab and cry3A genes is described in this study. The LAMP assay can be finished within 60 min at an isothermal condition of 63 °C. The derived LAMP products can be obtained by a real-time turbidimeter via monitoring the white turbidity or directly observed by the naked eye through adding SYBR Green I dye. The specificity of the LAMP assay was determined by analyzing thirteen insect-resistant genetically-modified (GM crop events with different Bt genes. Furthermore, the sensitivity of the LAMP assay was evaluated by diluting the template genomic DNA. Results showed that the limit of detection of the established LAMP assays was approximately five copies of haploid genomic DNA, about five-fold greater than that of conventional PCR assays. All of the results indicated that this established rapid and visual LAMP assay was quick, accurate and cost effective, with high specificity and sensitivity. In addition, this method does not need specific expensive instruments or facilities, which can provide a simpler and quicker approach to detecting the cry2Ab and cry3A genes in GM crops, especially for on-site, large-scale test purposes in the field.

Development and application of loop-mediated isothermal amplification assays for rapid visual detection of cry2Ab and cry3A genes in genetically-modified crops.

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Li, Feiwu; Yan, Wei; Long, Likun; Qi, Xing; Li, Congcong; Zhang, Shihong

2014-08-27

The cry2Ab and cry3A genes are two of the most important insect-resistant exogenous genes and had been widely used in genetically-modified crops. To develop more effective alternatives for the quick identification of genetically-modified organisms (GMOs) containing these genes, a rapid and visual loop-mediated isothermal amplification (LAMP) method to detect the cry2Ab and cry3A genes is described in this study. The LAMP assay can be finished within 60 min at an isothermal condition of 63 °C. The derived LAMP products can be obtained by a real-time turbidimeter via monitoring the white turbidity or directly observed by the naked eye through adding SYBR Green I dye. The specificity of the LAMP assay was determined by analyzing thirteen insect-resistant genetically-modified (GM) crop events with different Bt genes. Furthermore, the sensitivity of the LAMP assay was evaluated by diluting the template genomic DNA. Results showed that the limit of detection of the established LAMP assays was approximately five copies of haploid genomic DNA, about five-fold greater than that of conventional PCR assays. All of the results indicated that this established rapid and visual LAMP assay was quick, accurate and cost effective, with high specificity and sensitivity. In addition, this method does not need specific expensive instruments or facilities, which can provide a simpler and quicker approach to detecting the cry2Ab and cry3A genes in GM crops, especially for on-site, large-scale test purposes in the field.

Modulation at Age of Onset in Tunisian Huntington Disease Patients: Implication of New Modifier Genes

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Dorra Hmida-Ben Brahim

2014-01-01

Full Text Available Huntington’s disease (HD is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population.

Heritability of blood pressure traits and the genetic contribution to blood pressure variance explained by four blood-pressure-related genes.

NARCIS (Netherlands)

Rijn, M.J. van; Schut, A.F.; Aulchenko, Y.S.; Deinum, J.; Sayed-Tabatabaei, F.A.; Yazdanpanah, M.; Isaacs, A.; Axenovich, T.I.; Zorkoltseva, I.V.; Zillikens, M.C.; Pols, H.A.; Witteman, J.C.; Oostra, B.A.; Duijn, C.M. van

2007-01-01

OBJECTIVE: To study the heritability of four blood pressure traits and the proportion of variance explained by four blood-pressure-related genes. METHODS: All participants are members of an extended pedigree from a Dutch genetically isolated population. Heritability and genetic correlations of

A Single Meal Containing Raw, Crushed Garlic Influences Expression of Immunity- and Cancer-Related Genes in Whole Blood of Humans1234

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Charron, Craig S; Dawson, Harry D; Albaugh, George P; Solverson, Patrick M; Vinyard, Bryan T; Solano-Aguilar, Gloria I; Molokin, Aleksey; Novotny, Janet A

2015-01-01

Background: Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease. Objective: We designed a study to probe the mechanisms of garlic action in humans. Methods: We conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15 g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was collected before and 3 h after test meal consumption for gene expression analysis in whole blood. Illumina BeadArray was used to screen for genes of interest, followed by real-time quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6 cells were treated with a purified garlic extract (0.5 μL/mL), and mRNA was measured by qRT-PCR at 0, 3, 6, and 24 h. Results: The following 7 genes were found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1α (HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1), oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog (REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1) (P garlic, respectively). OSM is a pleiotropic cytokine that inhibits several tumor cell lines in culture. Conclusion: These data indicate that the bioactivity of garlic is multifaceted and includes activation of genes related to immunity, apoptosis, and xenobiotic metabolism in humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as NCT01293591. PMID:26423732

Evaluation of the effect of blood contamination on the compressive strength of MTA modified with hydration accelerators

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Kaveh Oloomi

2013-08-01

Full Text Available Objectives This study was performed to evaluate the effect of blood contamination on the compressive strength (CS of Root MTA (RMTA modified with Calcium chloride (CaCl2 and Disodium hydrogen phosphate (Na2HPO4 as setting accelerators over time. Materials and Methods A total of 110 cylindrical specimens of RMTA were divided into 6 experimental groups as follows: Group1, RMTA; Group 2, RMTA modified with CaCl2 (RMTA-C; Group 3, RMTA modified with Na2HPO4 (RMTA-N; Group 4, RMTA contaminated with blood; Group 5, RMTA-C contaminated with blood; Group 6, RMTA-N contaminated with blood. The CS of specimens in all groups was evaluated after 3 hr, 24 hr, and 1 wk. In the modified groups (groups 2, 3, 5, and 6 the CS of five specimens per group was also evaluated after 1 hr. Results Blood contamination significantly reduced the CS of all materials at all time intervals (p < 0.05. After 3 hr, the CS of specimens in the RMTA groups (with and without blood contamination was significantly lower than those in the RMTA-C and RMTA-N groups (p < 0.05. The CS values were not significantly different at the other time intervals. In all groups, the CS of specimens significantly increased over time (p < 0.05. Conclusions Blood contamination decreased the CS of both original and accelerated RMTA.

Role of Metabolic Genes in Blood Aluminum Concentrations of Jamaican Children with and without Autism Spectrum Disorder

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Mohammad H. Rahbar

2016-11-01

Full Text Available Aluminum is a neurotoxic metal with known health effects in animals and humans. Glutathione-S-transferase (GST genes and enzymes play a major role in detoxification of several heavy metals. Besides a direct relationship with oxidative stress; aluminum decreases GST enzyme activities. Using data from 116 Jamaican children; age 2–8 years; with Autism Spectrum Disorder (ASD and 116 sex- and age-matched typically developing (TD children; we investigated the association of polymorphisms in three GST genes (GSTP1; GSTM1; and GSTT1 with mean blood aluminum concentrations in children with and without ASD. Using log-transformed blood aluminum concentration as the dependent variable in a linear regression model; we assessed the additive and interactive effects of ASD status and polymorphisms in the three aforementioned GST genes in relation to blood aluminum concentrations. Although none of the additive effects were statistically significant (all p > 0.16; we observed a marginally significant interaction between GSTP1 Ile105Val (rs1695 and ASD status (p = 0.07; even after controlling for parental education level and consumption of avocado; root vegetables; and tuna (canned fish. Our findings indicate a significantly lower (p < 0.03 adjusted geometric mean blood aluminum concentration for TD children who had the Val/Val genotype (14.57 µg/L; compared with those with Ile/Ile or Ile/Val genotypes who had an adjusted geometric mean of 23.75 µg/L. However; this difference was not statistically significant among the ASD cases (p = 0.76. Our findings indicate that ASD status may be a potential effect modifier when assessing the association between GSTP1 rs1695 and blood aluminum concentrations among Jamaican children. These findings require replication in other populations.

Inter-arm blood pressure differences compared with ambulatory monitoring: a manifestation of the ‘white-coat’ effect?

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Martin, Una; Holder, Roger; Hodgkinson, James; McManus, Richard

2013-01-01

Background Inter-arm difference in blood pressure of >10 mmHg is associated with peripheral vascular disease, but it is unclear how much of the difference in sequential right and left arm blood pressure measurements might be due to a ‘white-coat’ effect. Aim To use ambulatory blood pressure monitoring (ABPM) to better understand the clinical significance of inter-arm differences in blood pressure. Design and setting Retrospective study in a teaching hospital in Birmingham. Method Anonymised clinical data collected from 784 patients attending a single hospital-based hypertension clinic were retrospectively analysed. Each participant had blood pressure measured sequentially in both arms, followed by ABPM over the subsequent 24 hours. Result Data were available for 710 (91%) patients, of whom 39.3% (279) had a blood pressure difference of 10 mmHg or more between each arm. Compared to daytime systolic ABPM, the difference was 25.1 mmHg using the arm with the highest reading, but only 15.5 mmHg if the lower reading was taken (mean difference 9.6 mmHg (95% confidence interval [CI] = 9.0 mmHg to 10.3 mmHg)). However, differences between mean right (20.7 mmHg) or left (19.9 mmHg) arm blood pressure and daytime systolic ABPM were very similar. Conclusion Compared with ABPM, use of the higher of the left and right arm readings measured sequentially appears to overestimate true mean blood pressure. As there is no significant difference in the extent of disparity with ABPM by left or right arm, this is unlikely to be due to arm dominance and may be due to the ‘white-coat’ effect reducing blood pressure on repeated measurement. Where a large inter-arm blood pressure difference is detected with sequential measurement, healthcare professionals should re-measure the blood pressure in the original arm. PMID:23561681

Association between white-coat effect and blunted dipping of nocturnal blood pressure.

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Bochud, Murielle; Bovet, Pascal; Vollenweider, Peter; Maillard, Marc; Paccaud, Fred; Wandeler, Gilles; Gabriel, Anne; Burnier, Michel

2009-10-01

In this study, we assessed whether the white-coat effect (difference between office and daytime blood pressure (BP)) is associated with nondipping (absence of BP decrease at night). Data were available in 371 individuals of African descent from 74 families selected from a population-based hypertension register in the Seychelles Islands and in 295 Caucasian individuals randomly selected from a population-based study in Switzerland. We used standard multiple linear regression in the Swiss data and generalized estimating equations to account for familial correlations in the Seychelles data. The prevalence of systolic and diastolic nondipping (rate was inversely associated with the difference between daytime and night-time heart rate in the two populations. These results did not change after adjustment for potential confounders. The white-coat effect is associated with BP nondipping. The similar associations between office-daytime values and daytime-night-time values for both BP and heart rate suggest that the sympathetic nervous system might play a role. Our findings also further stress the interest, for clinicians, of assessing the presence of a white-coat effect as a means to further identify patients at increased cardiovascular risk and guide treatment accordingly.

Effects of white noise on Callsign Acquisition Test and Modified Rhyme Test scores.

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Blue-Terry, Misty; Letowski, Tomasz

2011-02-01

The Callsign Acquisition Test (CAT) is a speech intelligibility test developed by the US Army Research Laboratory. The test has been used to evaluate speech transmission through various communication systems but has not been yet sufficiently standardised and validated. The aim of this study was to compare CAT and Modified Rhyme Test (MRT) performance in the presence of white noise across a range of signal-to-noise ratios (SNRs). A group of 16 normal-hearing listeners participated in the study. The speech items were presented at 65 dB(A) in the background of white noise at SNRs of -18, -15, -12, -9 and -6 dB. The results showed a strong positive association (75.14%) between the two tests, but significant differences between the CAT and MRT absolute scores in the range of investigated SNRs. Based on the data, a function to predict CAT scores based on existing MRT scores and vice versa was formulated. STATEMENT OF RELEVANCE: This work compares performance data of a common speech intelligibility test (MRT) with a new test (CAT) in the presence of white noise. The results here can be used as a part of the standardisation procedures and provide insights to the predictive capabilities of the CAT to quantify speech intelligibility communication in high-noise military environments.

Impact of grape pomace consumption on the blood lipid profile and liver genes associated with lipid metabolism of young rats.

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Yu, Jianmei; Bansode, Rishipal R; Smith, Ivy N; Hurley, Steven L

2017-08-01

Herein, we investigated the effects of grape pomace (GP) in diet on body weight, blood lipid profile, and expression of liver genes associated with lipid metabolism using a young rat model. In this study, twenty female Sprague-Dawley rats at 7 weeks of age were randomly divided into 4 groups, which were fed modified AIN-93G diets containing 0% (control), 6.9%, 13.8%, and 20.7% of GP for 10 weeks. Feed consumption and body weight were weekly determined. Blood samples were obtained at the beginning and end of the feeding period for cholesterol, alanine aminotransferase (ALT), and glucose analysis. At the end of the feeding period, all rats were fasted overnight and euthanized. Heart, kidney, and liver samples were obtained and weighed. Liver tissues were used for gene expression analysis. GP-containing diet did not influence the body weight of the rats. As GP content increased, blood triglyceride and very low density lipoprotein (VLDL) decreased (P consumption of a diet containing appropriate amount of GP may help in the reduction of body fat accumulation and prevention of obesity. This is the first study revealing the change in gene expression caused by long-term consumption of GP-containing diet.

Congenital and nosocomial sepsis in infants born in a regional perinatal unit: cause, outcome, and white blood cell response.

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Ohlsson, A; Vearncombe, M

1987-02-01

The incidence, cause, and outcome of sepsis and the white blood cell response were studied in 6315 infants born in a regional perinatal unit. The incidence of neonatal sepsis was 6.5 per 1000 live births. Congenital sepsis (12 cases) was overwhelming, with associated maternal infection (92%), neutropenia (75%), and high rate of mortality (50%). The most common organism was Escherichia coli (58%). Gestational age and birth weight were similar in survivors and nonsurvivors. There was a strong correlation between total white blood cell count and both mature and immature neutrophil counts in survivors but this correlation decreased substantially in neonates that died. Analysis of variance indicated that the means for polymorphonuclear leukocyte and immature neutrophil counts were significantly higher in survivors. Nosocomial sepsis (38 cases) occurred in premature low birth weight infants receiving invasive, intensive care. The most common organism was Staphylococcus epidermidis (76%). Total white blood cell, polymorphonuclear leukocyte, and immature neutrophil counts rose significantly in response to sepsis. None died. Prevention of congenital sepsis requires methods to detect early maternal-fetal infection. Providing granulocytes to neutropenic neonates with congenital sepsis might improve outcome.

Whole genome sequencing reveals a novel deletion variant in the KIT gene in horses with white spotted coat colour phenotypes.

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Dürig, N; Jude, R; Holl, H; Brooks, S A; Lafayette, C; Jagannathan, V; Leeb, T

2017-08-01

White spotting phenotypes in horses can range in severity from the common white markings up to completely white horses. EDNRB, KIT, MITF, PAX3 and TRPM1 represent known candidate genes for such phenotypes in horses. For the present study, we re-investigated a large horse family segregating a variable white spotting phenotype, for which conventional Sanger sequencing of the candidate genes' individual exons had failed to reveal the causative variant. We obtained whole genome sequence data from an affected horse and specifically searched for structural variants in the known candidate genes. This analysis revealed a heterozygous ~1.9-kb deletion spanning exons 10-13 of the KIT gene (chr3:77,740,239_77,742,136del1898insTATAT). In continuity with previously named equine KIT variants we propose to designate the newly identified deletion variant W22. We had access to 21 horses carrying the W22 allele. Four of them were compound heterozygous W20/W22 and had a completely white phenotype. Our data suggest that W22 represents a true null allele of the KIT gene, whereas the previously identified W20 leads to a partial loss of function. These findings will enable more precise genetic testing for depigmentation phenotypes in horses. © 2017 Stichting International Foundation for Animal Genetics.

Transgenic mosquitoes expressing a phospholipase A(2 gene have a fitness advantage when fed Plasmodium falciparum-infected blood.

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Ryan C Smith

Full Text Available Genetically modified mosquitoes have been proposed as an alternative strategy to reduce the heavy burden of malaria. In recent years, several proof-of-principle experiments have been performed that validate the idea that mosquitoes can be genetically modified to become refractory to malaria parasite development.We have created two transgenic lines of Anophelesstephensi, a natural vector of Plasmodium falciparum, which constitutively secrete a catalytically inactive phospholipase A2 (mPLA2 into the midgut lumen to interfere with Plasmodium ookinete invasion. Our experiments show that both transgenic lines expressing mPLA2 significantly impair the development of rodent malaria parasites, but only one line impairs the development of human malaria parasites. In addition, when fed on malaria-infected blood, mosquitoes from both transgenic lines are more fecund than non-transgenic mosquitoes. Consistent with these observations, cage experiments with mixed populations of transgenic and non-transgenic mosquitoes show that the percentage of transgenic mosquitoes increases when maintained on Plasmodium-infected blood.Our results suggest that the expression of an anti-Plasmodium effector gene gives transgenic mosquitoes a fitness advantage when fed malaria-infected blood. These findings have important implications for future applications of transgenic mosquito technology in malaria control.

Age and prior blood feeding of Anopheles gambiae influences their susceptibility and gene expression patterns to ivermectin-containing blood meals.

Science.gov (United States)

Seaman, Jonathan A; Alout, Haoues; Meyers, Jacob I; Stenglein, Mark D; Dabiré, Roch K; Lozano-Fuentes, Saul; Burton, Timothy A; Kuklinski, Wojtek S; Black, William C; Foy, Brian D

2015-10-15

Ivermectin has been proposed as a novel malaria transmission control tool based on its insecticidal properties and unique route of acquisition through human blood. To maximize ivermectin's effect and identify potential resistance/tolerance mechanisms, it is important to understand its effect on mosquito physiology and potential to shift mosquito population age-structure. We therefore investigated ivermectin susceptibility and gene expression changes in several age groups of female Anopheles gambiae mosquitoes. The effect of aging on ivermectin susceptibility was analyzed in three age groups (2, 6, and 14-days) of colonized female Anopheles gambiaemosquitoes using standard survivorship assays. Gene expression patterns were then analyzed by transcriptome sequencing on an Illumina HiSeq 2500 platform. RT-qPCR was used to validate transcriptional changes and also to examine expression in a different, colonized strain and in wild mosquitoes, both of which blood fed naturally on an ivermectin-treated person. Mosquitoes of different ages and blood meal history died at different frequencies after ingesting ivermectin. Mortality was lowest in 2-day old mosquitoes exposed on their first blood meal and highest in 6-day old mosquitoes exposed on their second blood meal. Twenty-four hours following ivermectin ingestion, 101 and 187 genes were differentially-expressed relative to control blood-fed, in 2 and 6-day groups, respectively. Transcription patterns of select genes were similar in membrane-fed, colonized, and naturally-fed wild vectors. Transcripts from several unexpected functional classes were highly up-regulated, including Niemann-Pick Type C (NPC) genes, peritrophic matrix-associated genes, and immune-response genes, and these exhibited different transcription patterns between age groups, which may explain the observed susceptibility differences. Niemann-Pick Type 2 genes were the most highly up-regulated transcripts after ivermectin ingestion (up to 160 fold) and

Direct and long-term detection of gene doping in conventional blood samples.

Science.gov (United States)

Beiter, T; Zimmermann, M; Fragasso, A; Hudemann, J; Niess, A M; Bitzer, M; Lauer, U M; Simon, P

2011-03-01

The misuse of somatic gene therapy for the purpose of enhancing athletic performance is perceived as a coming threat to the world of sports and categorized as 'gene doping'. This article describes a direct detection approach for gene doping that gives a clear yes-or-no answer based on the presence or absence of transgenic DNA in peripheral blood samples. By exploiting a priming strategy to specifically amplify intronless DNA sequences, we developed PCR protocols allowing the detection of very small amounts of transgenic DNA in genomic DNA samples to screen for six prime candidate genes. Our detection strategy was verified in a mouse model, giving positive signals from minute amounts (20 μl) of blood samples for up to 56 days following intramuscular adeno-associated virus-mediated gene transfer, one of the most likely candidate vector systems to be misused for gene doping. To make our detection strategy amenable for routine testing, we implemented a robust sample preparation and processing protocol that allows cost-efficient analysis of small human blood volumes (200 μl) with high specificity and reproducibility. The practicability and reliability of our detection strategy was validated by a screening approach including 327 blood samples taken from professional and recreational athletes under field conditions.

Gene frequencies of ABO and rhesus blood groups and ...

African Journals Online (AJOL)

The distribution and gene frequencies of ABO and rhesus (Rh) blood groups and haemoglobin variants for samples of the Nigerian population at Ogbomoso was determined. Data consisting of records of blood groups and haemoglobin types of different ages ranging from infants to adults for a period of 4 to 6 years (1995 ...

Gene expression analysis in human breast cancer associated blood vessels.

Directory of Open Access Journals (Sweden)

Dylan T Jones

Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases: An NHLBI Resource for the Gene Therapy Community

Science.gov (United States)

Skarlatos, Sonia I.

2012-01-01

Abstract The goals of the National Heart, Lung, and Blood Institute (NHLBI) Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases are to conduct gene transfer studies in monkeys to evaluate safety and efficiency; and to provide NHLBI-supported investigators with expertise, resources, and services to actively pursue gene transfer approaches in monkeys in their research programs. NHLBI-supported projects span investigators throughout the United States and have addressed novel approaches to gene delivery; “proof-of-principle”; assessed whether findings in small-animal models could be demonstrated in a primate species; or were conducted to enable new grant or IND submissions. The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases successfully aids the gene therapy community in addressing regulatory barriers, and serves as an effective vehicle for advancing the field. PMID:22974119

Molecular genetics of coat colour variations in White Galloway and White Park cattle.

Science.gov (United States)

Brenig, B; Beck, J; Floren, C; Bornemann-Kolatzki, K; Wiedemann, I; Hennecke, S; Swalve, H; Schütz, E

2013-08-01

White Galloway cattle exhibit three different white coat colour phenotypes, that is, well marked, strongly marked and mismarked. However, mating of individuals with the preferred well or strongly marked phenotype also results in offspring with the undesired mismarked and/or even fully black coat colour. To elucidate the genetic background of the coat colour variations in White Galloway cattle, we analysed four coat colour relevant genes: mast/stem cell growth factor receptor (KIT), KIT ligand (KITLG), melanocortin 1 receptor (MC1R) and tyrosinase (TYR). Here, we show that the coat colour variations in White Galloway cattle and White Park cattle are caused by a KIT gene (chromosome 6) duplication and aberrant insertion on chromosome 29 (Cs29 ) as recently described for colour-sided Belgian Blue. Homozygous (Cs29 /Cs29 ) White Galloway cattle and White Park cattle exhibit the mismarked phenotype, whereas heterozygous (Cs29 /wt29 ) individuals are either well or strongly marked. In contrast, fully black individuals are characterised by the wild-type chromosome 29. As known for other cattle breeds, mutations in the MC1R gene determine the red colouring. Our data suggest that the white coat colour variations in White Galloway cattle and White Park cattle are caused by a dose-dependent effect based on the ploidy of aberrant insertions and inheritance of the KIT gene on chromosome 29. © 2013 The Authors, Animal Genetics © 2013 Stichting International Foundation for Animal Genetics.

Inhibition effect of B7-H1 gene-modified regulatory dendritic cells on thyroid-associated ophthalmopathy in mice

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Hua-Xin Chen

2014-10-01

Full Text Available AIM:To construct adenovirus vector expressing mice B7-H1 gene, transfect dendritic cells(DCs, and to study the therapeutic effect of modified DC on thyroid-associated ophthalmopathy(TAOin mice.METHODS: We designed and constructed B7-H1 gene adenovirus expression vector, and transfected DCs from mouse bone marrow, tested the phenotype and function of modified DCs, identificated its negative regulation to immune responses. The modified DCs were infected the sicked mice. And then the immunotherapeutic effect of modified DCs to TAO were tested. RESULTS: B7-H1 gene adenovirus vector was constructed and transfected DCs from bone marrow. The titer of the recombinant adenovirus was 1.8×109PFU/mL. B7-H1 gene modified DCs characteristics of regulatory DCs, could inhibit positive immune responses. The inhibition proceeding of TAO into mice infected modified DCs, was obviously prior to the control mice. The gene modified DCs, maybe become the new immunotherapy biological agent to thy TAO.CONCLUSION: We constructed the expression of mouse B7-H1 gene adenovirus expressed vector successfully, transfected DCs,by vector have properties of regulatory DCs, inhibiting positive immune response and the occurrence and development of thyroid eye disease. Gene modified DCs, reveal potent to the treatment of thyroid eye disease.

Microbiological Safety of Minimally Processed White Radish in Modified Atmosphere Packaging Combined with Irradiation Treatment

International Nuclear Information System (INIS)

Kim, J.K.; Jo, C.U.; Kim, H.J.; Lee, J.W.; Hwang, H.J.; Byun, M.W.

2005-01-01

White radish was minimally processed, packed with air, CO@@@(100g), and CO@@@/N@@@(25/75%), and irradiated at 0, 1, and 2 kGy, and its microbiological quality and pH were investigated during storage for 2 weeks at 4℃. Irradiation significantly reduced total aerobic, coli-form, and lactic acid bacteria counts. Modified atmosphere packaging (MAP) enhanced microorganism control during storage. Acidity decreased by MAP but was restored during storage

Class B Gene Expression and the Modified ABC Model in Nongrass Monocots

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Akira Kanno

2007-01-01

Full Text Available The discovery of the MADS-box genes and the study of model plants such as Arabidopsis thaliana and Antirrhinum majus have greatly improved our understanding of the molecular mechanisms driving the diversity in floral development. The class B genes, which belong to the MADS-box gene family, are important regulators of the development of petals and stamens in flowering plants. Many nongrass monocot flowers have two whorls of petaloid organs, which are called tepals. To explain this floral morphology, the modified ABC model was proposed. This model was exemplified by the tulip, in which expansion and restriction of class B gene expression is linked to the transition of floral morphologies in whorl 1. The expression patterns of class B genes from many monocot species nicely fit this model; however, those from some species, such as asparagus, do not. In this review, we summarize the relationship between class B gene expression and floral morphology in nongrass monocots, such as Liliales (Liliaceae and Asparagales species, and discuss the applicability of the modified ABC model to monocot flowers.

No evidence that polymorphisms of the vanishing white matter disease genes are risk factors in multiple sclerosis

NARCIS (Netherlands)

Pronk, J.C.; Scheper, G.C.; Andel, R.J.; van Berkel, C.G.M.; Polman, C.H.; Uitdehaag, B.M.J.; van der Knaap, M.S.

2008-01-01

Febrile infections are known to cause exacerbations in the white matter disorders 'vanishing white matter' (VWM) and multiple sclerosis (MS). We hypothesized that polymorphisms in EIF2B1-5, the genes involved in VWM, might be risk factors for the development of MS or temperature sensitivity in

Modifiable risk factors promoting neurodegeneration is associated with two novel brain degradation markers measured in serum

DEFF Research Database (Denmark)

Neergaard, Jesper; Møller, Katrine Dragsbæk; Christiansen, Claus

2017-01-01

truncated tau fragments (Tau-A and Tau-C) in serum. Platelets, albumin and several modifiable risk factors, including Body Mass Index, high density lipoprotein and White Blood Cell count were associated with the serum level of tau fragments. The factors associated with tau in serum may promote...

Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.

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Peter R Sinnaeve

Full Text Available Systemic and local inflammation plays a prominent role in the pathogenesis of atherosclerotic coronary artery disease, but the relationship of whole blood gene expression changes with coronary disease remains unclear. We have investigated whether gene expression patterns in peripheral blood correlate with the severity of coronary disease and whether these patterns correlate with the extent of atherosclerosis in the vascular wall. Patients were selected according to their coronary artery disease index (CADi, a validated angiographical measure of the extent of coronary atherosclerosis that correlates with outcome. RNA was extracted from blood of 120 patients with at least a stenosis greater than 50% (CADi > or = 23 and from 121 controls without evidence of coronary stenosis (CADi = 0. 160 individual genes were found to correlate with CADi (rho > 0.2, P<0.003. Prominent differential expression was observed especially in genes involved in cell growth, apoptosis and inflammation. Using these 160 genes, a partial least squares multivariate regression model resulted in a highly predictive model (r(2 = 0.776, P<0.0001. The expression pattern of these 160 genes in aortic tissue also predicted the severity of atherosclerosis in human aortas, showing that peripheral blood gene expression associated with coronary atherosclerosis mirrors gene expression changes in atherosclerotic arteries. In conclusion, the simultaneous expression pattern of 160 genes in whole blood correlates with the severity of coronary artery disease and mirrors expression changes in the atherosclerotic vascular wall.

Transcriptome analysis of Pacific white shrimp (Litopenaeus vannamei) challenged by Vibrio parahaemolyticus reveals unique immune-related genes.

Science.gov (United States)

Qin, Zhendong; Babu, V Sarath; Wan, Quanyuan; Zhou, Meng; Liang, Risheng; Muhammad, Asim; Zhao, Lijuan; Li, Jun; Lan, Jiangfeng; Lin, Li

2018-06-01

Pacific white shrimp (Litopenaeus vannamei) is an important cultural species worldwide. However, Vibrio spp. infections have caused a great economic loss in Pacific white shrimp culture industry. The immune responses of Pacific white shrimp to the Vibrio spp. is not fully characterized. In this study, the transcriptomic profiles of L. vannamei hemocytes were explored by injecting with or without Vibrio parahaemolyticus. Totally, 42,632 high-quality unigenes were obtained from RNAseq data. Comparative genome analysis showed 2258 differentially expressed genes (DEGs) following the Vibrio challenge, including 1017 up-regulated and 1241 down-regulated genes. Eight DEGs were randomly selected for further validation by quantitative real-time RT-PCR (qRT-PCR) and the results showed that are consistent with the RNA-seq data. Due to the lack of predictable adaptive immunity, shrimps rely on an innate immune system to defend themselves against invading microbes by recognizing and clearing them through humoral and cellular immune responses. Here we focused our studies on the humoral immunity, five genes (SR, MNK, CTL3, GILT, and ALFP) were selected from the transcriptomic data, which were significantly up-regulated by V. parahaemolyticus infection. These genes were widely expressed in six different tissues and were up-regulated by both Gram negative bacteria (V. parahaemolyticus) and Gram positive bacteria (Staphylococcus aureus). To further extend our studies, we knock-down those five genes by dsRNA in L. vannamei and analyzed the functions of specific genes against V. parahaemolyticus and S. aureus by bacterial clearance analysis. We found that the ability of L. vannamei was significantly reduced in bacterial clearance when treated with those specific dsRNA. These results indicate that those five genes play essential roles in antibacterial immunity and have its specific functions against different types of pathogens. The obtained data will shed a new light on the immunity

Effects of modified detonation nanodiamonds on the biochemical composition of human blood.

Science.gov (United States)

Baron, A V; Puzyr, A P; Baron, I I; Bondar, V S

2013-04-01

In vitro experiments showed that protein and non-protein components of human blood serum could be absorbed on the surface of modified nanodiamonds obtained by detonation synthesis. The prospects of using nanodiamond as a new absorbent for hemodialysis, plasmapheresis, and laboratory diagnostics are discussed.

Genetic screening of spinal muscular atrophy using a real-time modified COP-PCR technique with dried blood-spot DNA.

Science.gov (United States)

Ar Rochmah, Mawaddah; Harahap, Nur Imma Fatimah; Niba, Emma Tabe Eko; Nakanishi, Kenta; Awano, Hiroyuki; Morioka, Ichiro; Iijima, Kazumoto; Saito, Toshio; Saito, Kayoko; Lai, Poh San; Takeshima, Yasuhiro; Takeuchi, Atsuko; Bouike, Yoshihiro; Okamoto, Maya; Nishio, Hisahide; Shinohara, Masakazu

2017-10-01

Spinal muscular atrophy (SMA) is a common neuromuscular disorder caused by mutations in SMN1. More than 95% of SMA patients carry homozygous SMN1 deletion. SMA is the leading genetic cause of infant death, and has been considered an incurable disease. However, a recent clinical trial with an antisense oligonucleotide drug has shown encouraging clinical efficacy. Thus, early and accurate detection of SMN1 deletion may improve prognosis of many infantile SMA patients. A total of 88 DNA samples (37 SMA patients, 12 carriers and 39 controls) from dried blood spots (DBS) on filter paper were analyzed. All participants had previously been screened for SMN genes by PCR restriction fragment length polymorphism (PCR-RFLP) using DNA extracted from freshly collected blood. DNA was extracted from DBS that had been stored at room temperature (20-25°C) for 1week to 5years. To ensure sufficient quality and quantity of DNA samples, target sequences were pre-amplified by conventional PCR. Real-time modified competitive oligonucleotide priming-PCR (mCOP-PCR) with the pre-amplified PCR products was performed for the gene-specific amplification of SMN1 and SMN2 exon 7. Compared with PCR-RFLP using DNA from freshly collected blood, results from real-time mCOP-PCR using DBS-DNA for detection of SMN1 exon 7 deletion showed a sensitivity of 1.00 (CI [0.87, 1.00])] and specificity of 1.00 (CI [0.90, 1.00]), respectively. We combined DNA extraction from DBS on filter paper, pre-amplification of target DNA, and real-time mCOP-PCR to specifically detect SMN1 and SMN2 genes, thereby establishing a rapid, accurate, and high-throughput system for detecting SMN1-deletion with practical applications for newborn screening. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Gene expression patterns in blood leukocytes discriminate patients with acute infections

Science.gov (United States)

Allman, Windy; Chung, Wendy; Mejias, Asuncion; Ardura, Monica; Glaser, Casey; Wittkowski, Knut M.; Piqueras, Bernard; Banchereau, Jacques; Palucka, A. Karolina; Chaussabel, Damien

2007-01-01

Each infectious agent represents a unique combination of pathogen-associated molecular patterns that interact with specific pattern-recognition receptors expressed on immune cells. Therefore, we surmised that the blood immune cells of individuals with different infections might bear discriminative transcriptional signatures. Gene expression profiles were obtained for 131 peripheral blood samples from pediatric patients with acute infections caused by influenza A virus, Gram-negative (Escherichia coli) or Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) bacteria. Thirty-five genes were identified that best discriminate patients with influenza A virus infection from patients with either E coli or S pneumoniae infection. These genes classified with 95% accuracy (35 of 37 samples) an independent set of patients with either influenza A, E coli, or S pneumoniae infection. A different signature discriminated patients with E coli versus S aureus infections with 85% accuracy (34 of 40). Furthermore, distinctive gene expression patterns were observed in patients presenting with respiratory infections of different etiologies. Thus, microarray analyses of patient peripheral blood leukocytes might assist in the differential diagnosis of infectious diseases. PMID:17105821

Obesity gene NEGR1 associated with white matter integrity in healthy young adults.

Science.gov (United States)

Dennis, Emily L; Jahanshad, Neda; Braskie, Meredith N; Warstadt, Nicholus M; Hibar, Derrek P; Kohannim, Omid; Nir, Talia M; McMahon, Katie L; de Zubicaray, Greig I; Montgomery, Grant W; Martin, Nicholas G; Toga, Arthur W; Wright, Margaret J; Thompson, Paul M

2014-11-15

Obesity is a crucial public health issue in developed countries, with implications for cardiovascular and brain health as we age. A number of commonly-carried genetic variants are associated with obesity. Here we aim to see whether variants in obesity-associated genes--NEGR1, FTO, MTCH2, MC4R, LRRN6C, MAP2K5, FAIM2, SEC16B, ETV5, BDNF-AS, ATXN2L, ATP2A1, KCTD15, and TNN13K--are associated with white matter microstructural properties, assessed by high angular resolution diffusion imaging (HARDI) in young healthy adults between 20 and 30 years of age from the Queensland Twin Imaging study (QTIM). We began with a multi-locus approach testing how a number of common genetic risk factors for obesity at the single nucleotide polymorphism (SNP) level may jointly influence white matter integrity throughout the brain and found a wide spread genetic effect. Risk allele rs2815752 in NEGR1 was most associated with lower white matter integrity across a substantial portion of the brain. Across the area of significance in the bilateral posterior corona radiata, each additional copy of the risk allele was associated with a 2.2% lower average FA. This is the first study to find an association between an obesity risk gene and differences in white matter integrity. As our subjects were young and healthy, our results suggest that NEGR1 has effects on brain structure independent of its effect on obesity. Copyright © 2014. Published by Elsevier Inc.

Genes located in a chromosomal inversion are correlated with territorial song in white-throated sparrows.

Science.gov (United States)

Zinzow-Kramer, W M; Horton, B M; McKee, C D; Michaud, J M; Tharp, G K; Thomas, J W; Tuttle, E M; Yi, S; Maney, D L

2015-11-01

The genome of the white-throated sparrow (Zonotrichia albicollis) contains an inversion polymorphism on chromosome 2 that is linked to predictable variation in a suite of phenotypic traits including plumage color, aggression and parental behavior. Differences in gene expression between the two color morphs, which represent the two common inversion genotypes (ZAL2/ZAL2 and ZAL2/ZAL2(m) ), may therefore advance our understanding of the molecular underpinnings of these phenotypes. To identify genes that are differentially expressed between the two morphs and correlated with behavior, we quantified gene expression and terrirorial aggression, including song, in a population of free-living white-throated sparrows. We analyzed gene expression in two brain regions, the medial amygdala (MeA) and hypothalamus. Both regions are part of a 'social behavior network', which is rich in steroid hormone receptors and previously linked with territorial behavior. Using weighted gene co-expression network analyses, we identified modules of genes that were correlated with both morph and singing behavior. The majority of these genes were located within the inversion, showing the profound effect of the inversion on the expression of genes captured by the rearrangement. These modules were enriched with genes related to retinoic acid signaling and basic cellular functioning. In the MeA, the most prominent pathways were those related to steroid hormone receptor activity. Within these pathways, the only gene encoding such a receptor was ESR1 (estrogen receptor 1), a gene previously shown to predict song rate in this species. The set of candidate genes we identified may mediate the effects of a chromosomal inversion on territorial behavior. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

A practical platform for blood biomarker study by using global gene expression profiling of peripheral whole blood.

Directory of Open Access Journals (Sweden)

Ze Tian

Full Text Available Although microarray technology has become the most common method for studying global gene expression, a plethora of technical factors across the experiment contribute to the variable of genome gene expression profiling using peripheral whole blood. A practical platform needs to be established in order to obtain reliable and reproducible data to meet clinical requirements for biomarker study.We applied peripheral whole blood samples with globin reduction and performed genome-wide transcriptome analysis using Illumina BeadChips. Real-time PCR was subsequently used to evaluate the quality of array data and elucidate the mode in which hemoglobin interferes in gene expression profiling. We demonstrated that, when applied in the context of standard microarray processing procedures, globin reduction results in a consistent and significant increase in the quality of beadarray data. When compared to their pre-globin reduction counterparts, post-globin reduction samples show improved detection statistics, lowered variance and increased sensitivity. More importantly, gender gene separation is remarkably clearer in post-globin reduction samples than in pre-globin reduction samples. Our study suggests that the poor data obtained from pre-globin reduction samples is the result of the high concentration of hemoglobin derived from red blood cells either interfering with target mRNA binding or giving the pseudo binding background signal.We therefore recommend the combination of performing globin mRNA reduction in peripheral whole blood samples and hybridizing on Illumina BeadChips as the practical approach for biomarker study.

A possible dominant white gene in Jersey cattle

Directory of Open Access Journals (Sweden)

Sponenberg D Phillip

2001-01-01

Full Text Available Abstract A white heifer ("Snow" was born in 1991 from coloured registered Jersey parents. She produced six calves sired by coloured Jersey bulls: three white bull calves, two white heifer calves, and one coloured bull calf. One of the white bull calves was mated with 40 Hereford × Friesian yearling heifers (white face, predominantly black body with some white patches. The 38 resulting calves included 16 white and 22 coloured calves. Twelve of the 16 white calves were heifers and four were bulls. Red or black spotting was recorded on some white calves. The results are consistent with an autosomal dominant mutant causing the white phenotype. The mutation appears to have arisen spontaneously in Snow, then passing to her white progeny and white grand-progeny. The white individuals varied from entirely white in a few cases, to most having some residual small areas of red or black pigmentation in patterns not typical of other reported white spotting patterns of cattle.

Agrobacterium-mediated transformation of modified antifreeze protein gene in strawberry

Directory of Open Access Journals (Sweden)

Srisulak Dheeranupattana

2005-07-01

Full Text Available The optimum condition for shoot regeneration from leaf explants of strawberry cultivar Tiogar was investigated. It was found that the best regeneration condition was MS medium containing N6-Benzyladenine (BA and 2,4-Dichlorophenoxy acetic acid (2,4-D at concentrations of 1 mg.l-1 and 0.2 mg.l-1, respectively. Antibiotics sensitivity test found that shoot regeneration from leaf explant was inhibited more than 90% at the concentration of kanamycin (Km as low as 5 mg.l-1. The modified gene encoding antifreeze protein isoform HPLC 6 was successfully constructed using codons which were optimally expressed in the strawberry plant. The antifreeze protein genes, naturally in plasmid pSW1 and modified in plasmid BB, were transformed to strawberry leaf explants by Agrobacterium tumefaciens LBA 4404. The strawberry plants, transformed with both AFP genes, were able to root in MS media containing 50 mg.l-1 Km, while no roots grew from nontransformed plant in this condition. Polymerase chain reaction indicated that the transgenes were integrated in the genome of transformants.

Ancestry as a potential modifier of gene expression in breast tumors from Colombian women.

Science.gov (United States)

Serrano-Gómez, Silvia J; Sanabria-Salas, María Carolina; Garay, Jone; Baddoo, Melody C; Hernández-Suarez, Gustavo; Mejía, Juan Carlos; García, Oscar; Miele, Lucio; Fejerman, Laura; Zabaleta, Jovanny

2017-01-01

Hispanic/Latino populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. The molecular profile of breast cancer has been widely described in non-Hispanic Whites but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B as defined by St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. We found 5 genes potentially modulated by genetic ancestry: ERBB2 (log2FC = 2.367, padjancestry (p = 0.02, B = 3.11). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.

The effect of the colostral cells on gene expression of cytokines in cord blood cells.

Science.gov (United States)

Hrdý, Jiří; Novotná, Olga; Kocourková, Ingrid; Prokešová, Ludmila

2017-11-01

Beneficial effect of maternal milk is acknowledged, but there is still question whether maternal milk from allergic mother is as good as from healthy one. In our study, we have assayed the effect of cells from colostrum of healthy and allergic mothers on gene expression of cytokines in cord blood cells of newborns of healthy and allergic mothers. Cytokines typical for Th1 (IL-2, IFN-gamma), Th2 (IL-4, IL-13), Tregs (IL-10, TGF-beta), and IL-8 were followed. We were not able to detect significant influence of colostral cells on gene expression of cytokines in cord blood after 2-day coculture using Transwell system. There was no difference in gene expression of cytokines in nonstimulated cord blood cells of newborns of healthy and allergic mothers, but generally increased gene expression of cytokines except IL-10 and TGF-beta after polyclonal stimulation was detected in cord blood cells of children of allergic mothers. There was no difference in IL-10 expression in stimulated cord blood cells of children of healthy and allergic mothers. Gene expression of TGF-beta was even decreased in stimulated cord blood cells of children of allergic mothers in comparison to healthy ones. We have not observed difference in the capacity of colostral cells of healthy and allergic mothers to influence gene expression of cytokines in cord blood cells, but we have described difference in the reactivity of cord blood cells between children of allergic and healthy mothers.

Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

OpenAIRE

Desjardins , Stephane; Belkai , Emilie; Crete , Dominique; Cordonnier , Laurie; Scherrmann , Jean-Michel; Noble , Florence; Marie-Claire , Cynthia

2008-01-01

International audience; Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, th...

Blood cell gene expression profiling in rheumatoid arthritis. Discriminative genes and effect of rheumatoid factor

DEFF Research Database (Denmark)

Bovin, Lone Frier; Rieneck, Klaus; Workman, Christopher

2004-01-01

To study the pathogenic importance of the rheumatoid factor (RF) in rheumatoid arthritis (RA) and to identify genes differentially expressed in patients and healthy individuals, total RNA was isolated from peripheral blood mononuclear cells (PBMC) from eight RF-positive and six RF-negative RA...... patients, and seven healthy controls. Gene expression of about 10,000 genes were examined using oligonucleotide-based DNA chip microarrays. The analyses showed no significant differences in PBMC expression patterns from RF-positive and RF-negative patients. However, comparisons of gene expression patterns...

Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids

OpenAIRE

Arpón, Ana; Milagro, Fermín I.; Razquin, Cristina; Corella, Dolores; Estruch, Ramón; Fitó, Montserrat; Marti, Amelia; Martínez-González, Miguel A.; Ros, Emilio; Salas-Salvadó, Jordi; Riezu-Boj, José-Ignacio; Martínez, J. Alfredo

2017-01-01

DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, wi...

Use of indium-111-labeled white blood cells in the diagnosis of diabetic foot infections

International Nuclear Information System (INIS)

Zeiger, L.S.; Fox, I.M.

1990-01-01

The diagnosis of bone infection in the patient with nonvirgin bone is a diagnostic dilemma. This is especially true in the diabetic patient with a soft tissue infection and an underlying osteoarthropathy. The authors present a retrospective study using the new scintigraphic technique of indium-111-labeled white blood cells as a method of attempting to solve this diagnostic dilemma

White blood cell fragments in platelet concentrates prepared by the platelet-rich plasma or buffy-coat methods

NARCIS (Netherlands)

Dijkstra-Tiekstra, M. J.; van der Schoot, C. E.; Pietersz, R. N. I.; Reesink, H. W.

2005-01-01

BACKGROUND AND OBJECTIVES: White blood cell (WBC) fragments in platelet concentrates (PCs) may induce allo-immunization in the recipient. MATERIALS AND METHODS: As the level of WBC fragments can differ between PCs produced using different methods, we compared PCs prepared by using the buffy-coat

Influence of Momordica charantia L. on the red and white blood cells labeling with 99mTc

International Nuclear Information System (INIS)

Brandao, Jose Odinilson de Caldas; Souza, Grace M. Lima de; Catanho, Maria T. Jansem de Almeida

2008-01-01

Full text: Momordica charantia L. is popularly known in Brazil as bitter melon and it's commonly used to treat several diseases as cancer, diabetes and to heal skin injuries. Many papers have been published showing the potential radio pharmacological activity of this plant due to its linkage with 99m Tc through some protein fractions of the extract. In this study, it was evaluated the influence of Momordica charantia L extract , labeling ( in vitro) of blood elements with sodium pertechnetate (Na 99m TcO 4 ). In the labeling of red blood cells (in vitro), blood samples were obtained from Wistar rats and incubated with different concentrations of M. charantia, for control group was used NaCl 0.9% and added stannous chloride (SnCl 2 ) and 99m Tc. The plasma fractions (P) and the cells (C) were separated and, also, precipitated with trichloroacetic acid at 5%, obtaining the soluble (SF) and insoluble (IF) fractions. The radioactivity rate (%ATl) of each fraction was calculated. The same methodology was applied for white blood cells but these cells were separated in advance by centrifugation at 1800 rpm during 15 minutes. There weren't alterations in the labeling of red blood cells in the concentrations tested of the extract when compared with the rate of the control group neither in the insoluble fractions. However, on the white blood cells it was noticed an increase in 99m Tc uptake in the presence of M. charantia extract. So its possible to conclude, based on previous results obtained by our group, that the M. charantia L. could be used to evaluate inflammatory processes. (author)

A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes

DEFF Research Database (Denmark)

de Jong, Simone; Boks, Marco P M; Fuller, Tova F

2012-01-01

Despite large-scale genome-wide association studies (GWAS), the underlying genes for schizophrenia are largely unknown. Additional approaches are therefore required to identify the genetic background of this disorder. Here we report findings from a large gene expression study in peripheral blood...... of schizophrenia patients and controls. We applied a systems biology approach to genome-wide expression data from whole blood of 92 medicated and 29 antipsychotic-free schizophrenia patients and 118 healthy controls. We show that gene expression profiling in whole blood can identify twelve large gene co......, and regulated by the major histocompatibility (MHC) complex, which is intriguing in light of the fact that common allelic variants from the MHC region have been implicated in schizophrenia. This suggests that the MHC increases schizophrenia susceptibility via altered gene expression of regulatory genes...

Dietary Fat, Fat Metabolizing Genes, and Prostate Cancer Risk in African-Americans and Whites

National Research Council Canada - National Science Library

Ingles, Sue A

2004-01-01

... African-Americans and whites in Los Angels County. In the first year of the study, we finished genotyping three LOX gene polymorphisms, including 12-LOX G1n261Arg, Ser322Asn, and the 5_LOX promoter Sp1 motif polymorphism...

Use of cDNA microarray to isolate differentially expressed genes in White Spot Virus infected shrimp (penaeus stylirostris)

OpenAIRE

Dhar, Arun K.; Klimpel, Kurt R.; Bullis, Robert A.; McClenaghan, Leroy R.

2006-01-01

White spot syndrome virus (WSSV), the etiologic agent of white spot disease, is currently the most important viral pathogen infecting penaeid shrimp worldwide. Since the initial report, white spot disease has caused losses of catastrophic proportion to shrimp aquaculture globally. Although considerable progress has been made in characterizing the WSSV and developing detection methods, information on the host genes involved in the immune response in shrimp due to WSSV infection is not availabl...

Altered gene expression in blood and sputum in COPD frequent exacerbators in the ECLIPSE cohort.

Directory of Open Access Journals (Sweden)

Dave Singh

Full Text Available Patients with chronic obstructive pulmonary disease (COPD who are defined as frequent exacerbators suffer with 2 or more exacerbations every year. The molecular mechanisms responsible for this phenotype are poorly understood. We investigated gene expression profile patterns associated with frequent exacerbations in sputum and blood cells in a well-characterised cohort. Samples from subjects from the ECLIPSE COPD cohort were used; sputum and blood samples from 138 subjects were used for microarray gene expression analysis, while blood samples from 438 subjects were used for polymerase chain reaction (PCR testing. Using microarray, 150 genes were differentially expressed in blood (>±1.5 fold change, p≤0.01 between frequent compared to non-exacerbators. In sputum cells, only 6 genes were differentially expressed. The differentially regulated genes in blood included downregulation of those involved in lymphocyte signalling and upregulation of pro-apoptotic signalling genes. Multivariate analysis of the microarray data followed by confirmatory PCR analysis identified 3 genes that predicted frequent exacerbations; B3GNT, LAF4 and ARHGEF10. The sensitivity and specificity of these 3 genes to predict the frequent exacerbator phenotype was 88% and 33% respectively. There are alterations in systemic immune function associated with frequent exacerbations; down-regulation of lymphocyte function and a shift towards pro-apoptosis mechanisms are apparent in patients with frequent exacerbations.

Allele frequencies of hemojuvelin gene (HJV I222N and G320V missense mutations in white and African American subjects from the general Alabama population

Directory of Open Access Journals (Sweden)

Bohannon Sean B

2004-12-01

Full Text Available Abstract Background Homozygosity or compound heterozygosity for coding region mutations of the hemojuvelin gene (HJV in whites is a cause of early age-of-onset iron overload (juvenile hemochromatosis, and of hemochromatosis phenotypes in some young or middle-aged adults. HJV coding region mutations have also been identified recently in African American primary iron overload and control subjects. Primary iron overload unexplained by typical hemochromatosis-associated HFE genotypes is common in white and black adults in Alabama, and HJV I222N and G320V were detected in a white Alabama juvenile hemochromatosis index patient. Thus, we estimated the frequency of the HJV missense mutations I222N and G320V in adult whites and African Americans from Alabama general population convenience samples. Methods We evaluated the genomic DNA of 241 Alabama white and 124 African American adults who reported no history of hemochromatosis or iron overload to detect HJV missense mutations I222N and G320V using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP technique. Analysis for HJV I222N was performed in 240 whites and 124 African Americans. Analysis for HJV G320V was performed in 241 whites and 118 African Americans. Results One of 240 white control subjects was heterozygous for HJV I222N; she was also heterozygous for HFE C282Y, but had normal serum iron measures and bone marrow iron stores. HJV I222N was not detected in 124 African American subjects. HJV G320V was not detected in 241 white or 118 African American subjects. Conclusions HJV I222N and G320V are probably uncommon causes or modifiers of primary iron overload in adult whites and African Americans in Alabama. Double heterozygosity for HJV I222N and HFE C282Y may not promote increased iron absorption.

Evaluation of endogenous control gene(s) for gene expression studies in human blood exposed to 60Co γ-rays ex vivo

International Nuclear Information System (INIS)

Vaiphei, S. Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Sharan, R.N.; Chaubey, R.C.; Kma, L.

2015-01-01

In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving 60 Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of 60 Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min -1 at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. (author)

Prepatterning of developmental gene expression by modified histones before zygotic genome activation

DEFF Research Database (Denmark)

Lindeman, Leif C.; Andersen, Ingrid S.; Reiner, Andrew H.

2011-01-01

A hallmark of anamniote vertebrate development is a window of embryonic transcription-independent cell divisions before onset of zygotic genome activation (ZGA). Chromatin determinants of ZGA are unexplored; however, marking of developmental genes by modified histones in sperm suggests a predictive...... role of histone marks for ZGA. In zebrafish, pre-ZGA development for ten cell cycles provides an opportunity to examine whether genomic enrichment in modified histones is present before initiation of transcription. By profiling histone H3 trimethylation on all zebrafish promoters before and after ZGA......, we demonstrate here an epigenetic prepatterning of developmental gene expression. This involves pre-ZGA marking of transcriptionally inactive genes involved in homeostatic and developmental regulation by permissive H3K4me3 with or without repressive H3K9me3 or H3K27me3. Our data suggest that histone...

Usefulness of estimation of blood procalcitonin concentration versus C-reactive protein concentration and white blood cell count for therapeutic monitoring of sepsis in neonates

Directory of Open Access Journals (Sweden)

Agnieszka Kordek

2014-12-01

Full Text Available Aim: This study was intended to assess the clinical usefulness of blood procalcitonin (PCT concentrations for the diagnosis and therapeutic monitoring of nosocomial neonatal sepsis.Material/Methods: The enrolment criterion was sepsis clinically manifesting after three days of life. PCT concentrations were measured in venous blood from 52 infected and 88 uninfected neonates. The results were interpreted against C-reactive protein (CRP concentrations and white blood cell counts (WBC.Results: Differences between the two groups in PCT and CRP concentrations were highly significant. No significant differences between the groups were noted for WBC. The threshold value on the receiver operator characteristic curve was 2.06 ng/mL for PCT (SE 75%; SP 80.68%; PPV 62.22%; NPV 88.75%; AUC 0.805, 5.0 mg/L for CRP (SE 67.44%; SP 73.68%; PPV 42.02%; NPV 88.89%; AUC 0.801, and 11.9 x109/L for WBC (SE 51.16%; SP 50.68%; PPV 23.16%; NPV 78.13%; AUC 0.484. Procalcitonin concentrations decreased 24 hours after initiation of antibiotic therapy and reverted to the control level after 5-7 days. C-reactive protein concentrations began to decline after two days of antibiotic therapy but were still higher than in the control group after 5-7 days of treatment. No significant changes in WBC during the treatment were observed.Conclusions: Procalcitonin concentrations in blood appear to be of use for the diagnosis and therapeutic monitoring of nosocomial infections in neonates as this parameter demonstrates greater sensitivity and specificity than C-reactive protein. White blood cell counts appear to be of little diagnostic value in the early phase of infection or for therapeutic monitoring.

Low Maternal Vitamin B12 Status Is Associated with Lower Cord Blood HDL Cholesterol in White Caucasians Living in the UK

Directory of Open Access Journals (Sweden)

Antonysunil Adaikalakoteswari

2015-04-01

Full Text Available Background and Aims: Studies in South Asian population show that low maternal vitamin B12 associates with insulin resistance and small for gestational age in the offspring. Low vitamin B12 status is attributed to vegetarianism in these populations. It is not known whether low B12 status is associated with metabolic risk of the offspring in whites, where the childhood metabolic disorders are increasing rapidly. Here, we studied whether maternal B12 levels associate with metabolic risk of the offspring at birth. Methods: This is a cross-sectional study of 91 mother-infant pairs (n = 182, of white Caucasian origin living in the UK. Blood samples were collected from white pregnant women at delivery and their newborns (cord blood. Serum vitamin B12, folate, homocysteine as well as the relevant metabolic risk factors were measured. Results: The prevalence of low serum vitamin B12 (<191 ng/L and folate (<4.6 μg/L were 40% and 11%, respectively. Maternal B12 was inversely associated with offspring’s Homeostasis Model Assessment 2-Insulin Resistance (HOMA-IR, triglycerides, homocysteine and positively with HDL-cholesterol after adjusting for age and BMI. In regression analysis, after adjusting for likely confounders, maternal B12 is independently associated with neonatal HDL-cholesterol and homocysteine but not triglycerides or HOMA-IR. Conclusions: Our study shows that low B12 status is common in white women and is independently associated with adverse cord blood cholesterol.

Blood-based gene-expression predictors of PTSD risk and resilience among deployed marines: a pilot study.

Science.gov (United States)

Glatt, Stephen J; Tylee, Daniel S; Chandler, Sharon D; Pazol, Joel; Nievergelt, Caroline M; Woelk, Christopher H; Baker, Dewleen G; Lohr, James B; Kremen, William S; Litz, Brett T; Tsuang, Ming T

2013-06-01

Susceptibility to PTSD is determined by both genes and environment. Similarly, gene-expression levels in peripheral blood are influenced by both genes and environment, and expression levels of many genes show good correspondence between peripheral blood and brain. Therefore, our objectives were to test the following hypotheses: (1) pre-trauma expression levels of a gene subset (particularly immune-system genes) in peripheral blood would differ between trauma-exposed Marines who later developed PTSD and those who did not; (2) a predictive biomarker panel of the eventual emergence of PTSD among high-risk individuals could be developed based on gene expression in readily assessable peripheral blood cells; and (3) a predictive panel based on expression of individual exons would surpass the accuracy of a model based on expression of full-length gene transcripts. Gene-expression levels were assayed in peripheral blood samples from 50 U.S. Marines (25 eventual PTSD cases and 25 non-PTSD comparison subjects) prior to their deployment overseas to war-zones in Iraq or Afghanistan. The panel of biomarkers dysregulated in peripheral blood cells of eventual PTSD cases prior to deployment was significantly enriched for immune genes, achieved 70% prediction accuracy in an independent sample based on the expression of 23 full-length transcripts, and attained 80% accuracy in an independent sample based on the expression of one exon from each of five genes. If the observed profiles of pre-deployment mRNA-expression in eventual PTSD cases can be further refined and replicated, they could suggest avenues for early intervention and prevention among individuals at high risk for trauma exposure. Copyright © 2013 Wiley Periodicals, Inc.

The state of glutathion system of blood, brain and liver of white rats after chronic gamma-irradiation

International Nuclear Information System (INIS)

Petushok, N.Eh.; Lashak, L.K.; Trebukhina, R.V.

1999-01-01

The effects of 3-fold gamma-irradiation in total dose 0,75 Gy on the glutathion system in different periods after exposure (1 hour, 1 day, 1 and 4 weeks) in blood, brain and liver of white rats were studied. It was concluded that liver and brain have higher ability to maintain the stability of antioxidant system than blood has. After shot disturbances caused by irradiation in brain and liver the state of glutathion system of detoxication has normalized, while concentration of malonic dialdehyde was raised in all terms. The most pronounced changes of antioxidant system were registered in blood at early terms (1 hour) after irradiation that was manifested in increasing of reduced glutathion content, raising of glutathion reductase and catalase activity. In remote period the activity of this system in blood was exhausted

POLYMORPHISMS OF ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE AS PREDICTORS OF WOLFF-PARKINSON-WHITE SYNDROME

Directory of Open Access Journals (Sweden)

G. V. Matyushin

2017-01-01

Full Text Available Background. The discovery of new genetic predictors of cardiovascular diseases can be used in predicting and diagnosing latent forms of the disease. Wolff-Parkinson-White syndrome (WPW occurs in all age groups  and detected in 1-30 people per 10000, it manifests mainly in young age (on average 20 years, and the risk of sudden cardiac death is higher than in general population.Aim. To study the relationship of WPW syndrome with the polymorphism of endothelial nitric synthase gene (NOS3, and to identify genetic predictors of this syndrome.Material and methods. The study included 51 people with ECG proven WPW syndrome and 153 people with no cardiovascular disease. The patients were divided into subgroups according to sex: 21 women, 30 men. All patients underwent a standard cardiac examination (anamnesis, electrocardiography, echocardiography, bicycle ergometry, transesophageal electrical stimulation of the atria, Holter monitoring and blood was taken for molecular genetic testing of DNA.Results. The results showed a statistically significant prevalence of rare genotype 4b\\4b NOS3 gene in the control group of women (16.3%; р<0.05 compared with women from the main group, who did not have this genotype, while there was significant prevalence of genotype 4a\\4a in the main group of women (81.0%; р<0.05 compared with women from the control group.  In men this prevalence was not found.Conclusion. The presence of genotype 4b\\4b NOS3 gene reduces the likelihood of WPW syndrome and its symptoms in females. In men,  this prevalence is not found, presumably, in connection with some mechanisms of hormonal regulation. The results can be used in the genetic prediction of the course of the disease.

Enhanced gene ranking approaches using modified trace ratio algorithm for gene expression data

Directory of Open Access Journals (Sweden)

Shruti Mishra

Full Text Available Microarray technology enables the understanding and investigation of gene expression levels by analyzing high dimensional datasets that contain few samples. Over time, microarray expression data have been collected for studying the underlying biological mechanisms of disease. One such application for understanding the mechanism is by constructing a gene regulatory network (GRN. One of the foremost key criteria for GRN discovery is gene selection. Choosing a generous set of genes for the structure of the network is highly desirable. For this role, two suitable methods were proposed for selection of appropriate genes. The first approach comprises a gene selection method called Information gain, where the dataset is reformed and fused with another distinct algorithm called Trace Ratio (TR. Our second method is the implementation of our projected modified TR algorithm, where the scoring base for finding weight matrices has been re-designed. Both the methods' efficiency was shown with different classifiers that include variants of the Artificial Neural Network classifier, such as Resilient Propagation, Quick Propagation, Back Propagation, Manhattan Propagation and Radial Basis Function Neural Network and also the Support Vector Machine (SVM classifier. In the study, it was confirmed that both of the proposed methods worked well and offered high accuracy with a lesser number of iterations as compared to the original Trace Ratio algorithm. Keywords: Gene regulatory network, Gene selection, Information gain, Trace ratio, Canonical correlation analysis, Classification

Evaluation of endogenous control gene(s) for gene expression studies in human blood exposed to 60Co γ-rays ex vivo.

Science.gov (United States)

Vaiphei, S Thangminlal; Keppen, Joshua; Nongrum, Saibadaiahun; Chaubey, R C; Kma, L; Sharan, R N

2015-01-01

In gene expression studies, it is critical to normalize data using a stably expressed endogenous control gene in order to obtain accurate and reliable results. However, we currently do not have a universally applied endogenous control gene for normalization of data for gene expression studies, particularly those involving (60)Co γ-ray-exposed human blood samples. In this study, a comparative assessment of the gene expression of six widely used housekeeping endogenous control genes, namely 18S, ACTB, B2M, GAPDH, MT-ATP6 and CDKN1A, was undertaken for a range of (60)Co γ-ray doses (0.5, 1.0, 2.0 and 4.0 Gy) at 8.4 Gy min(-1) at 0 and 24 h post-irradiation time intervals. Using the NormFinder algorithm, real-time PCR data obtained from six individuals (three males and three females) were analyzed with respect to the threshold cycle (Ct) value and abundance, ΔCt pair-wise comparison, intra- and inter-group variability assessments, etc. GAPDH, either alone or in combination with 18S, was found to be the most suitable endogenous control gene and should be used in gene expression studies, especially those involving qPCR of γ-ray-exposed human blood samples. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Role of eicosanoids and white blood cells in the beneficial effects of limited reperfusion after ischemia-reperfusion injury in skeletal muscle

International Nuclear Information System (INIS)

Anderson, R.J.; Cambria, R.A.; Dikdan, G.; Lysz, T.W.; Hobson, R.W. II

1990-01-01

Limiting the rate of reperfusion blood flow has been shown to be beneficial locally in models of ischemia-reperfusion injury. We investigated the effects of this on eicosanoids (thromboxane B2, 6-keto-PGF1 alpha, and leukotriene B4), white blood cell activation, and skeletal muscle injury as quantitated by triphenyltetrazolium chloride and technetium-99m pyrophosphate after ischemia-reperfusion injury in an isolated gracilis muscle model in 16 anesthetized dogs. One gracilis muscle in each dog was subjected to 6 hours of ischemia followed by 1 hour of limited reperfusion and then by a second hour of normal reperfusion. The other muscle was subjected to 6 hours of ischemia followed by 2 hours of normal reperfusion. Six dogs each were used as normal reperfusion controls (NR) and limited reperfusion controls (LR), with 5 dogs being treated with a thromboxane synthetase inhibitor (LR/TSI) and another five with a leukotriene inhibitor (LR/LI). LR in all three groups (LR, LR/TSI, and LR/LI) showed a benefit in skeletal muscle injury as measured by triphenyltetrazolim chloride and technetium-99m pyrophosphate when compared with NR. However, there was no significant difference between the groups with LR regarding eicosanoid levels and white blood cell activation when compared with NR. These results demonstrate that LR produces benefits by mechanisms other than those dependent upon thromboxane A2, prostacyclin, or white blood cell activation

Platelet-derived growth factor (PDGF) B-chain gene expression by activated blood monocytes precedes the expression of the PDGF A-chain gene

International Nuclear Information System (INIS)

Martinet, Y.; Jaffe, H.A.; Yamauchi, K.; Betsholtz, C.; Westermark, B.; Heldin, C.H.; Crystal, R.G.

1987-01-01

When activated, normal human blood monocytes are known to express the c-sis proto-oncogene coding for PDGF B-chain. Since normal human platelet PDGF molecules are dimers of A and B chains and platelets and monocytes are derived from the same marrow precursors, activated blood monocytes were simultaneously evaluated for their expression of PDGF A and B chain genes. Human blood monocytes were purified by adherence, cultured with or without activation by lipopolysaccharide and poly(A)+ RNA evaluated using Northern analysis and 32 P-labeled A-chain and B-chain (human c-sis) probes. Unstimulated blood monocytes did not express either A-chain or B-chain genes. In contrast, activated monocytes expressed a 4.2 kb mRNA B-chain transcript at 4 hr, but the B-chain mRNA levels declined significantly over the next 18 hr. In comparison, activated monocytes expressed very little A-chain mRNA at 4 hr, but at 12 hr 1.9, 2.3, and 2.8 kb transcripts were observed and persisted through 24 hr. Thus, activation of blood monocytes is followed by PDGF B-chain gene expression preceding PDGF A-chain gene expression, suggesting a difference in the regulation of the expression of the genes for these two chains by these cells

Gene frequencies of ABO and Rh blood groups in Nigeria: A review ...

African Journals Online (AJOL)

Background: ABO and Rhesus factor (Rh) blood type are germane in human life in genetics and clinical studies. Aim of the study: The review was undertaken with the objective to provide data on the ABO and Rh(D) blood group distribution and gene frequency across Nigeria which is vital for blood transfusion and ...

Critical biological parameters modulate affinity as a determinant of function in T-cell receptor gene-modified T-cells.

Science.gov (United States)

Spear, Timothy T; Wang, Yuan; Foley, Kendra C; Murray, David C; Scurti, Gina M; Simms, Patricia E; Garrett-Mayer, Elizabeth; Hellman, Lance M; Baker, Brian M; Nishimura, Michael I

2017-11-01

T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity. It is critical to re-evaluate the importance of other biophysical, structural, or cellular factors that drive the reactivity of TCR gene-modified T-cells. Using a model for altered antigen recognition, we determined how TCR-pMHC affinity influenced the reactivity of hepatitis C virus (HCV) TCR gene-modified T-cells against a panel of naturally occurring HCV peptides and HCV-expressing tumor targets. The impact of other factors, such as TCR-pMHC stabilization and signaling contributions by the CD8 co-receptor, as well as antigen and TCR density were also evaluated. We found that changes in TCR-pMHC affinity did not always predict or dictate IFNγ release or degranulation by TCR gene-modified T-cells, suggesting that less emphasis might need to be placed on TCR-pMHC affinity as a means of predicting or augmenting the therapeutic potential of TCR gene-modified T-cells used in ACT. A more complete understanding of antigen recognition by gene-modified T-cells and a more rational approach to improve the design and implementation of novel TCR-based immunotherapies is necessary to enhance efficacy and maximize safety in patients.

A "White" Anthocyanin-less Pomegranate (Punica granatum L.) Caused by an Insertion in the Coding Region of the Leucoanthocyanidin Dioxygenase (LDOX; ANS) Gene.

Science.gov (United States)

Ben-Simhon, Zohar; Judeinstein, Sylvie; Trainin, Taly; Harel-Beja, Rotem; Bar-Ya'akov, Irit; Borochov-Neori, Hamutal; Holland, Doron

2015-01-01

Color is an important determinant of pomegranate fruit quality and commercial value. To understand the genetic factors controlling color in pomegranate, chemical, molecular and genetic characterization of a "white" pomegranate was performed. This unique accession is lacking the typical pomegranate color rendered by anthocyanins in all tissues of the plant, including flowers, fruit (skin and arils) and leaves. Steady-state gene-expression analysis indicated that none of the analyzed "white" pomegranate tissues are able to synthesize mRNA corresponding to the PgLDOX gene (leucoanthocyanidin dioxygenase, also called ANS, anthocyanidin synthase), which is one of the central structural genes in the anthocyanin-biosynthesis pathway. HPLC analysis revealed that none of the "white" pomegranate tissues accumulate anthocyanins, whereas other flavonoids, corresponding to biochemical reactions upstream of LDOX, were present. Molecular analysis of the "white" pomegranate revealed the presence of an insertion and an SNP within the coding region of PgLDOX. It was found that the SNP does not change amino acid sequence and is not fully linked with the "white" phenotype in all pomegranate accessions from the collection. On the other hand, genotyping of pomegranate accessions from the collection and segregating populations for the "white" phenotype demonstrated its complete linkage with the insertion, inherited as a recessive single-gene trait. Taken together, the results indicate that the insertion in PgLDOX is responsible for the "white" anthocyanin-less phenotype. These data provide the first direct molecular, genetic and chemical evidence for the effect of a natural modification in the LDOX gene on color accumulation in a fruit-bearing woody perennial deciduous tree. This modification can be further utilized to elucidate the physiological role of anthocyanins in protecting the tree organs from harmful environmental conditions, such as temperature and UV radiation.

Regional cerebral blood flow measurements by a noninvasive microsphere method using 123I-IMP. Comparison with the modified fractional uptake method and the continuous arterial blood sampling method

International Nuclear Information System (INIS)

Nakano, Seigo; Matsuda, Hiroshi; Tanizaki, Hiroshi; Ogawa, Masafumi; Miyazaki, Yoshiharu; Yonekura, Yoshiharu

1998-01-01

A noninvasive microsphere method using N-isopropyl-p-( 123 I)iodoamphetamine ( 123 I-IMP), developed by Yonekura et al., was performed in 10 patients with neurological diseases to quantify regional cerebral blood flow (rCBF). Regional CBF values by this method were compared with rCBF values simultaneously estimated from both the modified fractional uptake (FU) method using cardiac output developed by Miyazaki et al. and the conventional method with continuous arterial blood sampling. In comparison, we designated the factor which converted raw SPECT voxel counts to rCBF values as a CBF factor. A highly significant correlation (r=0.962, p<0.001) was obtained in the CBF factors between the present method and the continuous arterial blood sampling method. The CBF factors by the present method were only 2.7% higher on the average than those by the continuous arterial blood sampling method. There were significant correlation (r=0.811 and r=O.798, p<0.001) in the CBF factor between modified FU method (threshold for estimating total brain SPECT counts; 10% and 30% respectively) and the continuous arterial blood sampling method. However, the CBF factors of the modified FU method showed 31.4% and 62.3% higher on the average (threshold; 10% and 30% respectively) than those by the continuous arterial blood sampling method. In conclusion, this newly developed method for rCBF measurements was considered to be useful for routine clinical studies without any blood sampling. (author)

Relationship of white blood cell counts, haemoglobin and ESR with IHD

International Nuclear Information System (INIS)

Shahzad, F.; Shahzad Tawwab, S.; Abbas, A.

2009-01-01

To find any association of white blood cells, haemoglobin and ESR with ischemic heart disease in high risk native population. Methodology: The study included 93 male patients with Ischemic heart disease, between 40 and 60 years of age; 96 age and gender matched subjects. All study participants were non-diabetics. Complete blood cells count, haemoglobin and ESR levels were compared between the patient and control groups. Results: Total leukocyte counts along with neutrophils were significantly higher in the test group compared to the control population (p<0.001) and lymphocytes were significantly lower (p<0.001) in the patient group as compared to the control group. Haemoglobin levels were significantly lower (p<0.001) and ESR was higher (p=0.030) in the patient group as compared to the control group. Conclusion: Although, our findings of the study variables extend previous reports, the prevalence and prognostic importance of theses variables in IHD should be assessed in future experimental studies. These parameters could be important in public health because they are routinely measured by clinicians and may be helpful to predict the risk of future and secondary ischemic events in a high risk population. (author)

Kearns-Sayre syndrome with facial and white matter extensive involvement: a (mitochondrial and nuclear gene related? neurocristopathy?

Directory of Open Access Journals (Sweden)

Agostino Berio

2017-12-01

Full Text Available The Authors report on a patient with Kearns-Sayre syndrome, large mtDNA deletion (7/kb, facial abnormalities and severe central nervous system (CNS white matter radiological features, commonly attributed to spongy alterations. The common origin from neural crest cell (NCC of facial structures (cartilagineous, osseous, vascular and of the peripheral nervous system and of peripheral glia and partially of the CNS white matter are underlined and the facial and glial abnormalities are attributed to the abnormal reproduction/migration of NCC. In this view, the CNS spongy alterations in KSS may be not only a dystrophic process (leukodystrophy but also a dysplastic condition (leukodysplasia. The Authors hypothesize that the symptoms may be related to mtDNA mutations associated to NCC nuclear gene abnormality. SOX 10 gene may be a nuclear candidate gene, as reported in some case of Waardenburg IV syndrome.

Locating a modifier gene of Ovum mutant through crosses between ...

Indian Academy of Sciences (India)

modifier gene of Om in the B6 background. [Tan J., Song ... should be half the rate of those from the normal crosses,. B6 (+/+) ... the genetic background of the B6 strain. The purpose of .... Smirnov test (P > 0.05) and the reproductive rate of N2.

Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

DEFF Research Database (Denmark)

Lassen, L.H.; Jacobsen, V.B.; Haderslev, P.A.

2008-01-01

Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...

Circadian gene expression in peripheral blood leukocytes of rotating night shift nurses.

Science.gov (United States)

Reszka, Edyta; Peplonska, Beata; Wieczorek, Edyta; Sobala, Wojciech; Bukowska, Agnieszka; Gromadzinska, Jolanta; Lie, Jenny-Anne; Kjuus, Helge; Wasowicz, Wojciech

2013-03-01

It has been hypothesized that the underlying mechanism of elevated breast cancer risk among long-term, night-working women involves circadian genes expression alteration caused by exposure to light at night and/or irregular work hours. The aim of the present study was to determine the effect of rotating night shift work on expression of selected core circadian genes. The cross-sectional study was conducted on 184 matched nurses and midwives, who currently work either day or rotating night shifts, to determine the effect of irregular work at night on circadian gene expression in peripheral blood leukocytes. Transcript levels of BMAL1, CLOCK, CRY1, CRY2, PER1, PER2, and PER3 were determined by means of quantitative real-time polymerase chain reaction (PCR). After adjusting for hour of blood collection, there were no statistically significant changes of investigated circadian genes among nurses and midwives currently working rotating night shifts compared to nurses working day shifts. The highest expression of PER1 messenger ribonucleic acid (mRNA) was observed for women currently working shifts who had worked >15 years in rotating night shift work. PER1 gene expression was associated with the lifetime duration of rotating night shift work among women currently working night shifts (P=0.04). PER1 and PER3 transcript levels in blood leukocytes were significantly down-regulated in the later versus early hours of the morning between 06.00-10.00 hours (β-coefficient -0.226, P=0.001 and β-coefficient -0.181, Pnight shift work does not affect circadian gene expression in human circulating leukocytes. In analysis of the peripheral clock in human studies, the hour of blood collection should be precisely specified.

PRAME Gene Expression in Acute Leukemia and Its Clinical Significance

International Nuclear Information System (INIS)

Ding, Kai; Wang, Xiao-ming; Fu, Rong; Ruan, Er-bao; Liu, Hui; Shao, Zong-hong

2012-01-01

To investigate the expression of the preferentially expressed antigen of melanoma (PRAME) gene in acute leukemia and its clinical significance. The level of expressed PRAME mRNA in bone marrow mononuclear cells from 34 patients with acute leukemia (AL) and in 12 bone marrow samples from healthy volunteers was measured via RT-PCR. Correlation analyses between PRAME gene expression and the clinical characteristics (gender, age, white blood count, immunophenotype of leukemia, percentage of blast cells, and karyotype) of the patients were performed. The PRAME gene was expressed in 38.2% of all 34 patients, in 40.7% of the patients with acute myelogenous leukemia (AML, n=27), and in 28.6% of the patients with acute lymphoblastic leukemia (ALL, n=7), but was not expressed in the healthy volunteers. The difference in the expression levels between AML and ALL patients was statistically significant. The rate of gene expression was 80% in M 3 , 33.3% in M 2 , and 28.6% in M 5 . Gene expression was also found to be correlated with CD15 and CD33 expression and abnormal karyotype, but not with age, gender, white blood count or percentage of blast cells. The PRAME gene is highly expressed in acute leukemia and could be a useful marker to monitor minimal residual disease. This gene is also a candidate target for the immunotherapy of acute leukemia

Association of duffy blood group gene polymorphisms with IL8 gene in chronic periodontitis.

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Emília Ângela Sippert

Full Text Available The antigens of the Duffy blood group system (DARC act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group gene polymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher's Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%, -845TC genotype (7.3% vs. 0.7% and the CTA haplotype (3.6% vs. 0.4% were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis.

Association of duffy blood group gene polymorphisms with IL8 gene in chronic periodontitis.

Science.gov (United States)

Sippert, Emília Ângela; de Oliveira e Silva, Cléverson; Visentainer, Jeane Eliete Laguila; Sell, Ana Maria

2013-01-01

The antigens of the Duffy blood group system (DARC) act as a receptor for the interleukin IL-8. IL-8 plays an important role in the pathogenesis of chronic periodontitis due to its chemotactic properties on neutrophils. The aim of this study was to investigate a possible association of Duffy blood group gene polymorphisms with the -353T>A, -845T>C and -738T>A SNPs of the IL8 gene in chronic periodontitis. One hundred and twenty-four individuals with chronic periodontitis and 187 controls were enrolled. DNA was extracted using the salting-out method. The Duffy genotypes and IL8 gene promoter polymorphisms were investigated by PCR-RFLP. Statistical analyses were conducted using the Chi square test with Yates correction or Fisher's Exact Test, and the possibility of associations were evaluated by odds ratio with a 95% confidence interval. When analyzed separately, for the Duffy blood group system, differences in the genotype and allele frequencies were not observed between all the groups analyzed; and, in nonsmokers, the -845C allele (3.6% vs. 0.4%), -845TC genotype (7.3% vs. 0.7%) and the CTA haplotype (3.6% vs. 0.4%) were positively associated with chronic periodontitis. For the first time to our knowledge, the polymorphisms of erythroid DARC plus IL8 -353T>A SNPs were associated with chronic periodontitis in Brazilian individuals. In Afro-Brazilians patients, the FY*02N.01 with IL8 -353A SNP was associated with protection to chronic periodontitis.

Gene-diet-interactions in folate-mediated one-carbon metabolism modify colon cancer risk.

Science.gov (United States)

Liu, Amy Y; Scherer, Dominique; Poole, Elizabeth; Potter, John D; Curtin, Karen; Makar, Karen; Slattery, Martha L; Caan, Bette J; Ulrich, Cornelia M

2013-04-01

The importance of folate-mediated one-carbon metabolism (FOCM) in colorectal carcinogenesis is emphasized by observations that high dietary folate intake is associated with decreased risk of colon cancer (CC) and its precursors. Additionally, polymorphisms in FOCM-related genes have been repeatedly associated with risk, supporting a causal relationship between folate and colorectal carcinogenesis. We investigated ten candidate polymorphisms with defined or probable functional impact in eight FOCM-related genes (SHMT1, DHFR, DNMT1, MTHFD1, MTHFR, MTRR, TCN2, and TDG) in 1609 CC cases and 1974 controls for association with CC risk and for interaction with dietary factors. No polymorphism was statistically significantly associated with overall risk of CC. However, statistically significant interactions modifying CC risk were observed for DNMT1 I311V with dietary folate, methionine, vitamin B2 , and vitamin B12 intake and for MTRR I22M with dietary folate, a predefined one-carbon dietary pattern, and vitamin B6 intake. We observed statistically significant gene-diet interactions with five additional polymorphisms. Our results provide evidence that FOCM-related dietary intakes modify the association between CC risk and FOCM allelic variants. These findings add to observations showing that folate-related gene-nutrient interactions play an important role in modifying the risk of CC. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ambulatory blood pressure monitoring profile in urban African black and European white untreated hypertensive patients matched for age and sex.

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Polónia, Jorge; Madede, Tavares; Silva, José A; Mesquita-Bastos, José; Damasceno, Albertino

2014-08-01

The aim of this study was to compare the 24-h ambulatory blood pressure (ABP) profile in never-treated black hypertensive patients living in Africa, Mozambique (20-80 years), versus never-treated white hypertensive patients living in Europe. ABP recordings of untreated black hypertensive patients and white hypertensive patients with 24-h ABP of 130/80 mmHg or more were retrospectively selected from two computerized database records of ABP and matched for age by decades, sex, and BMI. Black hypertensive patients were n=548, 47 ± 12 years, 52% women, BMI=28.0 ± 8.2 kg/m(2), 7% smokers, 7% diabetics; white hypertensive patients were n=604, 47 ± 15 years, 52% women, BMI=27.4 ± 5.1 kg/m(2), 8.4% diabetics, and 18% smokers (Pwhite hypertensive patients showed higher casual blood pressure (BP) 160/104 ± 19/14 versus 149/97 ± 18/12 mmHg, 24-h ABP 146/92 ± 16/13 versus 139/85 ± 11/10 mmHg, daytime ABP 150/95 ± 16/13 versus 143/88 ± 13/11 mmHg, night-time BP 139/84 ± 17/13 versus 130/78 ± 13/10 mmHg (all Pwhite hypertensive patients for all spectra of age distribution. This might be the reason for the worse cardiovascular prognosis described in black hypertensive patients compared with white hypertensive patients.

Development of antibody-modified chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier as a strategy for inhibiting HIV replication in astrocytes.

Science.gov (United States)

Gu, Jijin; Al-Bayati, Karam; Ho, Emmanuel A

2017-08-01

RNA interference (RNAi)-mediated gene silencing offers a novel treatment and prevention strategy for human immunodeficiency virus (HIV) infection. HIV was found to infect and replicate in human brain cells and can cause neuroinfections and neurological deterioration. We designed dual-antibody-modified chitosan/small interfering RNA (siRNA) nanoparticles to deliver siRNA across the blood-brain barrier (BBB) targeting HIV-infected brain astrocytes as a strategy for inhibiting HIV replication. We hypothesized that transferrin antibody and bradykinin B2 antibody could specifically bind to the transferrin receptor (TfR) and bradykinin B2 receptor (B2R), respectively, and deliver siRNA across the BBB into astrocytes as potential targeting ligands. In this study, chitosan nanoparticles (CS-NPs) were prepared by a complex coacervation method in the presence of siRNA, and antibody was chemically conjugated to the nanoparticles. The antibody-modified chitosan nanoparticles (Ab-CS-NPs) were spherical in shape, with an average particle size of 235.7 ± 10.2 nm and a zeta potential of 22.88 ± 1.78 mV. The therapeutic potential of the nanoparticles was evaluated based on their cellular uptake and gene silencing efficiency. Cellular accumulation and gene silencing efficiency of Ab-CS-NPs in astrocytes were significantly improved compared to non-modified CS-NPs and single-antibody-modified CS-NPs. These results suggest that the combination of anti-Tf antibody and anti-B2 antibody significantly increased the knockdown effect of siRNA-loaded nanoparticles. Thus, antibody-mediated dual-targeting nanoparticles are an efficient and promising delivery strategy for inhibiting HIV replication in astrocytes. Graphical abstract Graphic representation of dual-antibody-conjugated chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier (BBB) for inhibiting HIV replication in astrocytes. a Nanoparticle delivery to the BBB and penetration. b Tf

Modified cyanobacteria

Science.gov (United States)

Vermaas, Willem F J.

2014-06-17

Disclosed is a modified photoautotrophic bacterium comprising genes of interest that are modified in terms of their expression and/or coding region sequence, wherein modification of the genes of interest increases production of a desired product in the bacterium relative to the amount of the desired product production in a photoautotrophic bacterium that is not modified with respect to the genes of interest.

Aging: a portrait from gene expression profile in blood cells.

Science.gov (United States)

Calabria, Elisa; Mazza, Emilia Maria Cristina; Dyar, Kenneth Allen; Pogliaghi, Silvia; Bruseghini, Paolo; Morandi, Carlo; Salvagno, Gian Luca; Gelati, Matteo; Guidi, Gian Cesare; Bicciato, Silvio; Schiaffino, Stefano; Schena, Federico; Capelli, Carlo

2016-08-01

The availability of reliable biomarkers of aging is important not only to monitor the effect of interventions and predict the timing of pathologies associated with aging but also to understand the mechanisms and devise appropriate countermeasures. Blood cells provide an easily available tissue and gene expression profiles from whole blood samples appear to mirror disease states and some aspects of the aging process itself. We report here a microarray analysis of whole blood samples from two cohorts of healthy adult and elderly subjects, aged 43±3 and 68±4 years, respectively, to monitor gene expression changes in the initial phase of the senescence process. A number of significant changes were found in the elderly compared to the adult group, including decreased levels of transcripts coding for components of the mitochondrial respiratory chain, which correlate with a parallel decline in the maximum rate of oxygen consumption (VO2max), as monitored in the same subjects. In addition, blood cells show age-related changes in the expression of several markers of immunosenescence, inflammation and oxidative stress. These findings support the notion that the immune system has a major role in tissue homeostasis and repair, which appears to be impaired since early stages of the aging process.

Catecholamine-related gene expression in blood correlates with tic severity in tourette syndrome.

Science.gov (United States)

Gunther, Joan; Tian, Yingfang; Stamova, Boryana; Lit, Lisa; Corbett, Blythe; Ander, Brad; Zhan, Xinhua; Jickling, Glen; Bos-Veneman, Netty; Liu, Da; Hoekstra, Pieter; Sharp, Frank

2012-12-30

Tourette syndrome (TS) is a heritable disorder characterized by tics that are decreased in some patients by treatment with alpha adrenergic agonists and dopamine receptor blockers. Thus, this study examines the relationship between catecholamine gene expression in blood and tic severity. TS diagnosis was confirmed using Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and tic severity measured using the Yale Global Tic Severity Scale (YGTSS) for 26 un-medicated subjects with TS. Whole blood was collected and Ribonucleic acid (RNA) processed on Affymetrix Human Exon 1.0 ST arrays. An Analysis of Covariance (ANCOVA) identified 3627 genes correlated with tic severity (pdisorders, Attention Deficit Hyperactivity Disorder (ADHD), and Obsessive-Compulsive Disorder (OCD). Correlation of gene expression in peripheral blood with tic severity may allow inferences about catecholamine pathway dysfunction in TS subjects. Findings built on previous work suggest that at least some genes expressed peripherally are relevant for central nervous system (CNS) pathology in the brain of individuals with TS. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Divergence With Age in Blood Pressure in African-Caribbean and White Populations in England: Implications for Screening for Hypertension

NARCIS (Netherlands)

Agyemang, Charles; Humphry, Roger W.; Bhopal, Raj

2012-01-01

BACKGROUND We assessed when blood pressure (BP) and hypertension begin to rise in African-Caribbeans compared to the white population; and whether the change relates to body mass index (BMI). METHODS Secondary analysis of the cross-sectional Health Surveys for England among 22,723 participants

Spaceflight modulates gene expression in the whole blood of astronauts.

Science.gov (United States)

Barrila, Jennifer; Ott, C Mark; LeBlanc, Carly; Mehta, Satish K; Crabbé, Aurélie; Stafford, Phillip; Pierson, Duane L; Nickerson, Cheryl A

2016-01-01

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1 , HSP27 , GPX1 , XRCC1 , BAG-1 , HHR23A , FAP48 , and C-FOS . No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight.

Sleep duration modifies effects of free ad libitum school meals on adiposity and blood pressure

DEFF Research Database (Denmark)

Hjorth, Mads Fiil; Sjödin, Anders Mikael; Dalskov, Stine-Mathilde

2016-01-01

.03;0.38) kg, android fat mass by 0.02 (0.001;0.04) kg, waist circumference by 0.73 (0.23;1.24) cm, blood pressure by 1.5 (0.4;2.6) mmHg, fat intake by 1.1 (0.2;2.0) energy %, and decreased total physical activity by 7.2 (1.6;12.7) % (all P≤0.04), while HOMAIR and blood lipids were not modified by sleep...

The Relationship between Birthweight and Longitudinal Changes of Blood Pressure Is Modulated by Beta-Adrenergic Receptor Genes: The Bogalusa Heart Study

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Wei Chen

2010-01-01

Full Text Available This study examines the genetic influence of β-adrenergic receptor gene polymorphisms (β2-AR Arg16Gly and β3-AR Trp64Arg on the relationship of birthweight to longitudinal changes of blood pressure (BP from childhood to adulthood in 224 black and 515 white adults, aged 21–47 years, enrolled in the Bogalusa Heart Study. Blacks showed significantly lower birthweight and frequencies of β2-AR Gly16 and β3-AR Trp64 alleles and higher BP levels and age-related trends than whites. In multivariable regression analyses using race-adjusted BP and birthweight, low birthweight was associated with greater increase in age-related trend of systolic BP (standardized regression coefficient β=−0.09, P=.002 and diastolic BP (β=−0.07, P=.037 in the combined sample of blacks and whites, adjusting for the first BP measurement in childhood, sex, age, and gestational age. Adjustment for the current body mass index strengthened the birthweight-BP association. Importantly, the strength of the association, measured as regression coefficients, was modulated by the combination of β2-AR and β3-AR genotypes for systolic (P=.042 for interaction and diastolic BP age-related trend (P=.039 for interaction, with blacks and whites showing a similar trend in the interaction. These findings indicate that the intrauterine programming of BP regulation later in life depends on β-AR genotypes.

Cord Blood Ischemia-Modified Albumin Levels in Normal and Intrauterine Growth Restricted Pregnancies

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Nicoletta Iacovidou

2008-01-01

Full Text Available Ischemia-modified albumin (IMA is a sensitive biomarker of cardiac ischemia. Intrauterine growth restriction (IUGR may imply fetal hypoxia, resulting in blood flow centralization in favour of vital organs (brain, heart, adrenals—‘‘brain sparing effect’’. Based on the latter, we hypothesized that cord blood IMA levels should not differ between IUGR and appropriate-for-gestational-age (AGA full-term pregnancies. IMA was measured in blood samples from doubly-clamped umbilical cords of 110 AGA and 57 asymmetric IUGR pregnancies. No significant differences in IMA levels were documented between AGA and IUGR groups. IMA levels were elevated in cases of elective cesarean section (P = .035, and offspring of multigravidas (P = .021. In conclusion, ‘‘brain sparing effect’’ is possibly responsible for the lack of differences in cord blood IMA levels at term, between IUGR and AGA groups. Furthermore, higher oxidative stress could account for the elevated IMA levels in cases of elective cesarean section, and offspring of multigravidas.

Ambient particulate air pollution induces oxidative stress and alterations of mitochondria and gene expression in brown and white adipose tissues

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Harkema Jack R

2011-07-01

Full Text Available Abstract Background Prior studies have demonstrated a link between air pollution and metabolic diseases such as type II diabetes. Changes in adipose tissue and its mitochondrial content/function are closely associated with the development of insulin resistance and attendant metabolic complications. We investigated changes in adipose tissue structure and function in brown and white adipose depots in response to chronic ambient air pollutant exposure in a rodent model. Methods Male ApoE knockout (ApoE-/- mice inhaled concentrated fine ambient PM (PM 2.5 or filtered air (FA for 6 hours/day, 5 days/week, for 2 months. We examined superoxide production by dihydroethidium staining; inflammatory responses by immunohistochemistry; and changes in white and brown adipocyte-specific gene profiles by real-time PCR and mitochondria by transmission electron microscopy in response to PM2.5 exposure in different adipose depots of ApoE-/- mice to understand responses to chronic inhalational stimuli. Results Exposure to PM2.5 induced an increase in the production of reactive oxygen species (ROS in brown adipose depots. Additionally, exposure to PM2.5 decreased expression of uncoupling protein 1 in brown adipose tissue as measured by immunohistochemistry and Western blot. Mitochondrial number was significantly reduced in white (WAT and brown adipose tissues (BAT, while mitochondrial size was also reduced in BAT. In BAT, PM2.5 exposure down-regulated brown adipocyte-specific genes, while white adipocyte-specific genes were differentially up-regulated. Conclusions PM2.5 exposure triggers oxidative stress in BAT, and results in key alterations in mitochondrial gene expression and mitochondrial alterations that are pronounced in BAT. We postulate that exposure to PM2.5 may induce imbalance between white and brown adipose tissue functionality and thereby predispose to metabolic dysfunction.

Meta-analysis of peripheral blood gene expression modules for COPD phenotypes.

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Dominik Reinhold

Full Text Available Chronic obstructive pulmonary disease (COPD occurs typically in current or former smokers, but only a minority of people with smoking history develops the disease. Besides environmental factors, genetics is an important risk factor for COPD. However, the relationship between genetics, environment and phenotypes is not well understood. Sample sizes for genome-wide expression studies based on lung tissue have been small due to the invasive nature of sample collection. Increasing evidence for the systemic nature of the disease makes blood a good alternative source to study the disease, but there have also been few large-scale blood genomic studies in COPD. Due to the complexity and heterogeneity of COPD, examining groups of interacting genes may have more relevance than identifying individual genes. Therefore, we used Weighted Gene Co-expression Network Analysis to find groups of genes (modules that are highly connected. However, module definitions may vary between individual data sets. To alleviate this problem, we used a consensus module definition based on two cohorts, COPDGene and ECLIPSE. We studied the relationship between the consensus modules and COPD phenotypes airflow obstruction and emphysema. We also used these consensus module definitions on an independent cohort (TESRA and performed a meta analysis involving all data sets. We found several modules that are associated with COPD phenotypes, are enriched in functional categories and are overrepresented for cell-type specific genes. Of the 14 consensus modules, three were strongly associated with airflow obstruction (meta p ≤ 0.0002, and two had some association with emphysema (meta p ≤ 0.06; some associations were stronger in the case-control cohorts, and others in the cases-only subcohorts. Gene Ontology terms that were overrepresented included "immune response" and "defense response." The cell types whose type-specific genes were overrepresented in modules (p < 0.05 included

Total white blood cell counts and LPS-induced TNF alpha production by monocytes of pregnant, pseudopregnant and cyclic rats

NARCIS (Netherlands)

Faas, MM; Moes, H; van der Schaaf, G; de Leij, LFMH; Heineman, MJ

Pregnancy in the rat may be associated with an activated innate immune system. Therefore, we investigated monocyte function as well as total white blood cell (WBC) counts during the follicular phase of the ovarian cycle, pregnancy and pseudopregnancy in the rat. Rats were equipped with a permanent

Total white blood cell counts and LPS-induced TNF alpha production by monocytes of pregnant, pseudopregnant and cyclic rats

NARCIS (Netherlands)

Faas, M. M.; Moes, H.; van der Schaaf, G.; de Leij, L. F. M. H.; Heineman, M. J.

2003-01-01

Pregnancy in the rat may be associated with an activated innate immune system. Therefore, we investigated monocyte function as well as total white blood cell (WBC) counts during the follicular phase of the ovarian cycle, pregnancy and pseudopregnancy in the rat. Rats were equipped with a permanent

Activation of anthocyanin synthesis genes by white light in eggplant hypocotyl tissues, and identification of an inducible P-450 cDNA

International Nuclear Information System (INIS)

Toguri, T.; Umemoto, N.; Kobayashi, O.; Ohtani, T.

1993-01-01

Eggplant seedlings (Solanum melongena) grown under red light irradiation showed a normal morphology with green, fully expanded cotyledons. When the seedlings grown under red light were irradiated with ultraviolet-containing white light, anthocyanin synthesis was induced in the hypocotyl tissues, especially when a UV light supplement was added. The accumulation of pigments was closely associated with the expression of genes involved in flavonoid synthesis. These genes include chalcone synthase (CHS) and dihydroflavonol 4-reductase (DFR). Using subtracted probes, which had been enriched for the accumulated mRNA, one white light-responsive cDNA was identified as being a P450 gene by comparison with database sequences. The maximal amino acid homology this cDNA had with other P450s was 36%. This was with CYP71 from avocado (Persea americana). Thus it represents a new P-450 family, which has been named CYP75. The mRNA of this gene was localized in the hypocotyl tissues of eggplant seedlings, which had been white light-irradiated. The transcript was accumulated by changing the light source, as in the case of other flavonoid biosynthesis genes. In delphinidin producing petunia plants, the mRNAs corresponding to the eggplant P-450 and flavonoid biosynthesis genes such as CHS and DFR were most abundant during the mid stage of flower bud development, but could not be detected in leaf tissues. These results suggest that this P-450 gene encodes a hydroxylating enzyme involved in flavonoid biosynthesis. (author)

Responses of proenkephalin Peptide F to aerobic exercise stress in the plasma and white blood cell biocompartments.

Science.gov (United States)

Kraemer, William J; Fragala, Maren S; van Henegouwen, Wendy R H Beijersbergen; Gordon, Scott E; Bush, Jill A; Volek, Jeff S; Triplett, N Travis; Dunn-Lewis, Courtenay; Comstock, Brett A; Szivak, Tunde K; Flanagan, Shawn D; Hooper, David R; Luk, Hui-Ying; Mastro, Andrea M

2013-04-01

Proenkephalin Peptide F [107-140] is an enkephalin-containing peptide found predominantly within the adrenal medulla, co-packaged with epinephrine within the chromaffin granules. In vivo studies indicate that Peptide F has classic opioid analgesia effects; in vitro studies suggest potential immune cell interactions. In this investigation we examined patterns of Peptide F concentrations in different bio-compartments of the blood at rest and following sub-maximal cycle exercise to determine if Peptide F interacts with the white blood cell (WBC) bio-compartment during aerobic exercise. Eight physically active men (n=8) performed sub-maximal (80-85% V˙O2peak) cycle ergometer exercise for 30 min. Plasma Peptide F and WBC Peptide F immunoreactivity were examined pre-exercise, mid-exercise and immediately post-, 5-min post-, 15-min post-, 30-min post- and 60-min post-exercise and at similar time-points during a control condition (30 min rest). Peptide F concentrations significantly (pexercise, compared to pre-exercise concentrations. No significant increases in Peptide F concentrations in the WBC fraction were observed during or after exercise. However, a significant decrease was observed at 30 min post-exercise. An ultradian pattern of Peptide F distribution was apparent during rest. Furthermore, concentrations of T cells, B cells, NK cells, and total WBCs demonstrated significant changes in response to aerobic exercise. Data indicated that Peptide F was bound in significant molar concentrations in the WBC fraction and that this biocompartment may be one of the tissue targets for binding interactions. These data indicate that Peptide F is involved with immune cell modulation in the white blood circulatory biocompartment of blood. Copyright © 2013. Published by Elsevier Inc.

Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation.

Science.gov (United States)

Arnardottir, Erna S; Nikonova, Elena V; Shockley, Keith R; Podtelezhnikov, Alexei A; Anafi, Ron C; Tanis, Keith Q; Maislin, Greg; Stone, David J; Renger, John J; Winrow, Christopher J; Pack, Allan I

2014-10-01

To address whether changes in gene expression in blood cells with sleep loss are different in individuals resistant and sensitive to sleep deprivation. Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 h of continuous wakefulness and subsequent recovery sleep, for a total of 19 time-points per subject, with every 2-h psychomotor vigilance task (PVT) assessment when awake. Sleep laboratory. Fourteen subjects who were previously identified as behaviorally resistant (n = 7) or sensitive (n = 7) to sleep deprivation by PVT. Thirty-eight hours of continuous wakefulness. We found 4,481 unique genes with a significant 24-h diurnal rhythm during a normal sleep-wake cycle in blood (false discovery rate [FDR] sleep. After accounting for circadian effects, two genes (SREBF1 and CPT1A, both involved in lipid metabolism) exhibited small, but significant, linear changes in expression with the duration of sleep deprivation (FDR sleep deprivation was a reduction in the amplitude of the diurnal rhythm of expression of normally cycling probe sets. This reduction was noticeably higher in behaviorally resistant subjects than sensitive subjects, at any given P value. Furthermore, blood cell type enrichment analysis showed that the expression pattern difference between sensitive and resistant subjects is mainly found in cells of myeloid origin, such as monocytes. Individual differences in behavioral effects of sleep deprivation are associated with differences in diurnal amplitude of gene expression for genes that show circadian rhythmicity. © 2014 Associated Professional Sleep Societies, LLC.

Enhanced regulatory gene expressions in the blood and articular cartilage of patients with rheumatoid arthritis

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Elena Vasilyevna Chetina

2012-01-01

Full Text Available Objective: to study the expression ratio of the non-tissue specific regulatory genes mTOR, р21, ATG1, caspase 3, tumor necrosis factor-а (TNF-а, and interleukin-6 (IL-6, as well as matrix metalloproteinase 13 (MMP-13 and X type collagen (COL10A1, cartilage resorption-associated MMP13 and COL10A1 in the blood and knee articular cartilage in patients with rheumatoid arthritis (RA. Subjects and methods. Twenty-five specimens of the distal femoral articular cartilage condyles were studied in 15 RA patients (mean age 52.4+9.1 years after endoprosthetic knee joint replacement and in 10 healthy individuals (mean age 36.0+9.1 years included into the control group. Twenty-eight blood samples taken from 28 RA patients (aged 52+7.6 years prior to endoprosthetic knee joint replacement and 27 blood samples from healthy individuals (mean age 53.6+8.3 years; a control group were also analyzed. Real-time quantitative polymerase chain reaction was applied to estimate the expression of the mTOR, p21, ATG1, caspase 3, TNF-а, IL- 6, COL0A1, and MMP-13 genes. The levels of a protein equivalent in the p70-S6K(activated by mTOR, p21, and caspase 3 genes concerned was measured in the isolated lymphocyte lysates, by applying the commercially available ELISA kits. Total protein in the cell extracts was determined using the Bradford assay procedure. Results. The cartilage samples from patients with end-stage RA exhibited a significantly higher mTOR, ATG1, p21, TNFа, MMP-13, and COL10A1 gene expressions than did those from the healthy individuals. At the same time, IL6 gene expression was much lower than that in the control group. The expressions of the mTOR, ATG1, p21, TNFа, and IL 6 genes in the blood of RA patients were much greater than those in the donors. Caspase 3 expression did not differ essentially in the bloods of the patients with RA and healthy individuals. The bloods failed to show MMP-13 and COL10A1 expressions. High mTOR and p21 gene expressions were

NOS3 Glu298Asp genotype and blood pressure response to endurance training: the HERITAGE family study.

Science.gov (United States)

Rankinen, T; Rice, T; Pérusse, L; Chagnon, Y C; Gagnon, J; Leon, A S; Skinner, J S; Wilmore, J H; Rao, D C; Bouchard, C

2000-11-01

Endothelium-dependent vasodilation is a mechanism that may affect blood pressure response to endurance training. Because NO plays a central role in this process, the endothelial NO synthase gene is a good candidate for the regulation of exercise blood pressure. We investigated the associations between an endothelial NO synthase gene polymorphism (Glu298Asp) and endurance training-induced changes in resting and submaximal exercise blood pressure in 471 white subjects of the HERITAGE Family Study. Two submaximal exercise tests at 50 W were conducted both before and after a 20-week endurance training program. Steady-state exercise blood pressure was measured twice in each test with an automated unit. The Glu298Asp polymorphism was typed with a PCR-based method and digestion with BAN:II. Both systolic and diastolic blood pressure at 50 W decreased in response to the training program, whereas resting blood pressure remained unchanged. The decrease in diastolic blood pressure at 50 W was greater (P=0.0005, adjusted for age, gender, baseline body mass index, and baseline diastolic blood pressure at 50 W) in the Glu/Glu homozygotes (4.4 [SEM 0.4] mm Hg, n=187) than in the heterozygotes (3.1 [0.4] mm Hg, n=213) and the Asp/Asp homozygotes (1.3 [0.7] mm Hg, n=71). The genotype accounted for 2.3% of the variance in diastolic blood pressure at 50 W training response. Both the Glu298 homozygotes and the heterozygotes had a greater (P=0.013) training-induced reduction in rate-pressure product at 50 W than the Asp298 homozygotes. These data suggest that DNA sequence variation in the endothelial NO synthase gene locus is associated with the endurance training-induced decreases in submaximal exercise diastolic blood pressure and rate-pressure product in sedentary normotensive white subjects.

Drug-gene interaction between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and antihypertensive therapy

NARCIS (Netherlands)

Schelleman, Hedi; Klungel, Olaf H; van Duijn, Cornelia M; Witteman, Jacqueline C M; Hofman, Albert; de Boer, Anthonius; Stricker, Bruno H Ch

BACKGROUND: Despite the availability of a variety of effective drugs, inadequate control of blood pressure is common. There are some indications that the angiotensin-converting enzyme (ACE) gene modifies the response to antihypertensive drugs, but the results have been inconclusive. OBJECTIVE: To

Data-driven asthma endotypes defined from blood biomarker and gene expression data.

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Barbara Jane George

Full Text Available The diagnosis and treatment of childhood asthma is complicated by its mechanistically distinct subtypes (endotypes driven by genetic susceptibility and modulating environmental factors. Clinical biomarkers and blood gene expression were collected from a stratified, cross-sectional study of asthmatic and non-asthmatic children from Detroit, MI. This study describes four distinct asthma endotypes identified via a purely data-driven method. Our method was specifically designed to integrate blood gene expression and clinical biomarkers in a way that provides new mechanistic insights regarding the different asthma endotypes. For example, we describe metabolic syndrome-induced systemic inflammation as an associated factor in three of the four asthma endotypes. Context provided by the clinical biomarker data was essential in interpreting gene expression patterns and identifying putative endotypes, which emphasizes the importance of integrated approaches when studying complex disease etiologies. These synthesized patterns of gene expression and clinical markers from our research may lead to development of novel serum-based biomarker panels.

False positive indium-111 white blood cell scan in a closed clavicle fracture

International Nuclear Information System (INIS)

Friedman, R.J.; Gordon, L.

1988-01-01

Aggressive treatment of the multiply injured patient often requires early fixation of many fractures, some of which may be open. Often, patients develop postoperative fevers requiring a thorough workup to rule out infection. Recently, indium-111 white blood cell (WBC) imaging has become a valuable adjunct in the diagnosis of acute infection. The patient described had a simple, closed clavicle fracture with markedly increased activity on an indium-111 WBC scan obtained for fever workup. This subsequently proved to be a normal, healing, noninfected fracture by other diagnostic techniques. Noninfected, simple closed fractures should be added to the list of causes for a false-positive indium-111 WBC scan

Image acquisition and interpretation criteria for Tc-99m-HMPAO-labelled white blood cell scintigraphy : results of a multicentre study

NARCIS (Netherlands)

Erba, Paola A.; Glaudemans, Andor W. J. M.; Veltman, Niels C.; Sollini, Martina; Pacilio, Marta; Galli, Filippo; Dierckx, Rudi A. J. O.; Signore, Alberto

Purpose There is no consensus yet on the best protocol for planar image acquisition and interpretation of radiolabelled white blood cell (WBC) scintigraphy. This may account for differences in reported diagnostic accuracy amongst different centres. Methods This was a multicentre retrospective study

On Orbit Immuno-Based, Label-Free, White Blood Cell Counting System with MicroElectroMechanical Sensor (MEMS) Technology (OILWBCS-MEMS), Phase II

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National Aeronautics and Space Administration — Aurora Flight Sciences Corporation and partner, Draper Laboratory, propose to develop an on-orbit immuno-based label-free white blood cell counting system using MEMS...

On Orbit Immuno-Based, Label-Free, White Blood Cell Counting System with MicroElectroMechanical Sensor (MEMS) Technology (OILWBCS-MEMS), Phase I

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National Aeronautics and Space Administration — Aurora Flight Sciences Corporation and our partner, Draper Laboratory, propose to develop an on orbit immuno-based, label-free, white blood cell counting system for...

Blood pressure effects of high-dose amlodipine-benazepril combination in Black and White hypertensive patients not controlled on monotherapy.

Science.gov (United States)

Chrysant, Steven G

2012-06-01

Black hypertensive patients are more resistant to angiotensin-converting enzyme (ACE) inhibitor monotherapy than White patients. This resistance can be overcome with the combination of ACE inhibitors with diuretics or calcium-channel blockers (CCBs). The objective of this clinical investigation was to evaluate the antihypertensive effectiveness of monotherapy with the ACE inhibitor benazepril or the CCB amlodipine and their combination in Black and White hypertensive patients in two separate studies. This was a post hoc analysis of data from two separate studies, pooled because of their similarities, to increase the sample size. Outpatient Black and White hypertensive patients were selected for these studies. In study H2303, 201 patients of both sexes and races, whose mean seated diastolic blood pressure (MSDBP) was ≥95 mmHg after 4 weeks of single-blind treatment with benazepril 40 mg/day, were randomized into two groups. Group 1 received benazepril 40 mg/day and group 2 received amlodipine/benazepril 5/40 mg/day, which was uptitrated to amlodipine/benazepril 10/40 mg/day at week 4 of the study. In study H2304, 812 similar patients, whose MSDBP was ≥95 mmHg after 4 weeks of single-blind treatment with amlodipine 10 mg/day, were randomized into three groups. Group 1 received amlodipine/benazepril 10/20 mg/day, uptitrated to amlodipine/benazepril 10/40 mg/day after 2 weeks. Group 2 received amlodipine/benazepril 10/20 mg/day. Group 3 received amlodipine 10 mg/day. All three groups were followed up for 6 additional weeks. This report presents the results of post hoc analysis of pooled data from two separate but similar studies. Combination therapy resulted in greater lowering of MSDBP and mean seated systolic blood pressure (MSSBP) than monotherapy with either benazepril or amlodipine (p benazepril 10/20 mg/day resulted in greater blood pressure (BP) reductions in White patients than in Black patients (p benazepril 10/40�

Longevity of rAAV vector and plasmid DNA in blood after intramuscular injection in nonhuman primates: implications for gene doping.

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Ni, W; Le Guiner, C; Gernoux, G; Penaud-Budloo, M; Moullier, P; Snyder, R O

2011-07-01

Legitimate uses of gene transfer technology can benefit from sensitive detection methods to determine vector biodistribution in pre-clinical studies and in human clinical trials, and similar methods can detect illegitimate gene transfer to provide sports-governing bodies with the ability to maintain fairness. Real-time PCR assays were developed to detect a performance-enhancing transgene (erythropoietin, EPO) and backbone sequences in the presence of endogenous cellular sequences. In addition to developing real-time PCR assays, the steps involved in DNA extraction, storage and transport were investigated. By real-time PCR, the vector transgene is distinguishable from the genomic DNA sequence because of the absence of introns, and the vector backbone can be identified by heterologous gene expression control elements. After performance of the assays was optimized, cynomolgus macaques received a single dose by intramuscular (IM) injection of plasmid DNA, a recombinant adeno-associated viral vector serotype 1 (rAAV1) or a rAAV8 vector expressing cynomolgus macaque EPO. Macaques received a high plasmid dose intended to achieve a significant, but not life-threatening, increase in hematocrit. rAAV vectors were used at low doses to achieve a small increase in hematocrit and to determine the limit of sensitivity for detecting rAAV sequences by single-step PCR. DNA extracted from white blood cells (WBCs) was tested to determine whether WBCs can be collaterally transfected by plasmid or transduced by rAAV vectors in this context, and can be used as a surrogate marker for gene doping. We demonstrate that IM injection of a conventional plasmid and rAAV vectors results in the presence of DNA that can be detected at high levels in blood before rapid elimination, and that rAAV genomes can persist for several months in WBCs.

White-coat, masked and sustained hypertension detected by home blood pressure monitoring in adolescents: prevalence and associated factors.

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Jardim, Thiago Veiga; Carneiro, Carolina de Souza; Morais, Polyana; Roriz, Vanessa; Mendonça, Karla Lorena; Nascente, Flávia Miquetichuc; Póvoa, Thaís Inácio Rolim; Barroso, Weimar Kunz Sebba; Sousa, Ana Luiza Lima; Jardim, Paulo César Veiga

2018-06-01

Population-based studies estimating prevalence's of white-coat, masked and sustained hypertension in non-European adolescents are needed, particularly in developing countries. Aiming to determine these estimates and, additionally identify factors associated to these conditions this study was conducted. Cross-sectional study with a representative sample of secondary school students from a Brazilian state capital. Office measurements were performed with validated semi-automatic devices. Home BP (blood pressure) monitoring protocol included two day-time and two evening-time measurements over 6 days. Adolescents' were classified as: normotensives (office and home BP coat hypertensives (office BP ≥95th percentile and home BP coat, masked and sustained hypertension. In a sample of 1024 adolescents, prevalence of white-coat, masked and sustained hypertension was 7.5%, 2.2% and 1.7%, respectively. Male sex was positively associated with white-coat hypertension (OR 2.68; 95%CI 1.58-4.54; p coat (OR 1.23; 95%CI 1.16-1.30; p coat hypertension, masked and sustained hypertension in a population of non-European adolescents assessed by home BP monitoring was 7.5%, 2.2% and 1.7% respectively. Male sex was positively associated with white-coat hypertension in these adolescents while BMI was positively associated with both white-coat and sustained hypertension.

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study

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Muhie Seid Y

2009-12-01

Full Text Available Abstract Background Preterm delivery (PTD is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk. Methods As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age from 14 women who had PTD (cases and 16 women who delivered at term (controls. Gene expressions were measured using the GeneChip® Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes. Results A total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa, were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1, TFAP2A (transcription factor AP2A, Sp1 (specificity protein 1 and Sp3 (specificity protein 3 were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes. Conclusions PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD

A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.

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Simone de Jong

Full Text Available Despite large-scale genome-wide association studies (GWAS, the underlying genes for schizophrenia are largely unknown. Additional approaches are therefore required to identify the genetic background of this disorder. Here we report findings from a large gene expression study in peripheral blood of schizophrenia patients and controls. We applied a systems biology approach to genome-wide expression data from whole blood of 92 medicated and 29 antipsychotic-free schizophrenia patients and 118 healthy controls. We show that gene expression profiling in whole blood can identify twelve large gene co-expression modules associated with schizophrenia. Several of these disease related modules are likely to reflect expression changes due to antipsychotic medication. However, two of the disease modules could be replicated in an independent second data set involving antipsychotic-free patients and controls. One of these robustly defined disease modules is significantly enriched with brain-expressed genes and with genetic variants that were implicated in a GWAS study, which could imply a causal role in schizophrenia etiology. The most highly connected intramodular hub gene in this module (ABCF1, is located in, and regulated by the major histocompatibility (MHC complex, which is intriguing in light of the fact that common allelic variants from the MHC region have been implicated in schizophrenia. This suggests that the MHC increases schizophrenia susceptibility via altered gene expression of regulatory genes in this network.

GAD1 Gene Expression in Blood of Patients with First-Episode Psychosis.

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Jie Yin Yee

Full Text Available γ-Aminobutyric acid (GABA, the primary inhibitory neurotransmitter, has often been studied in relation to its role in the pathophysiology of schizophrenia. GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD, derived from two genes, GAD1 and GAD2. GAD1 is expressed as both GAD67 and GAD25 mRNA transcripts with the former reported to have a lower expression level in schizophrenia compared to healthy controls and latter was reported to be predominantly expressed fetally, suggesting a role in developmental process. In this study, GAD67 and GAD25 mRNA levels were measured by quantitative PCR (qPCR in peripheral blood of subjects with first-episode psychosis (FEP and from healthy controls. We observed low GAD25 and GAD67 gene expression levels in human peripheral blood. There was no difference in GAD25 and GAD67 gene expression level, and GAD25/GAD67 ratio between patients with FEP and healthy controls. PANSS negative symptoms were associated with levels of GAD25 mRNA transcripts in patients with FEP. While the current study provides information on GAD25 and GAD67 mRNA transcript levels in whole blood of FEP patients, further correlation and validation work between brain regions, cerebrospinal fluid and peripheral blood expression profiling are required to provide a better understanding of GAD25 and GAD67.

Seasonal changes in the expression of energy metabolism-related genes in white adipose tissue and skeletal muscle in female Japanese black bears.

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Shimozuru, Michito; Nagashima, Akiko; Tanaka, Jun; Tsubota, Toshio

2016-01-01

Bears undergo annual cycles in body mass: rapid fattening in autumn (i.e., hyperphagia), and mass loss in winter (i.e., hibernation). To investigate how Japanese black bears (Ursus thibetanus japonicus) adapt to such extreme physiological conditions, we analyzed changes in the mRNA expression of energy metabolism-related genes in white adipose tissues and skeletal muscle throughout three physiological stages: normal activity (June), hyperphagia (November), and hibernation (March). During hyperphagia, quantitative real-time polymerase chain reaction analysis revealed the upregulation of de novo lipogenesis-related genes (e.g., fatty acid synthase and diacylglycerol O-acyltransferase 2) in white adipose tissue, although the bears had been maintained with a constant amount of food. In contrast, during the hibernation period, we observed a downregulation of genes involved in glycolysis (e.g., glucose transporter 4) and lipogenesis (e.g., acetyl-CoA carboxylase 1) and an upregulation of genes in fatty acid catabolism (e.g., carnitine palmitoyltransferase 1A) in both tissue types. In white adipose tissues, we observed upregulation of genes involved in glyceroneogenesis, including pyruvate carboxylase and phosphoenolpyruvate carboxykinase 1, suggesting that white adipose tissue plays a role in the recycling of circulating free fatty acids via re-esterification. In addition, the downregulation of genes involved in amino acid catabolism (e.g., alanine aminotransferase) and the TCA cycle (e.g., pyruvate carboxylase) indicated a role of skeletal muscle in muscle protein sparing and pyruvate recycling via the Cori cycle. These examples of coordinated transcriptional regulation would contribute to rapid mass gain during the pre-hibernation period and to energy preservation and efficient energy production during the hibernation period. Copyright © 2016 Elsevier Inc. All rights reserved.

HPRT gene locus mutation in peripheral blood lymphocytes induced by internal exposure to radionuclides

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Jingyong, Zhao; Yongzhong, Xu; Tao, Zhao; Fengmei, Cui; Liuyi, Wang; Qinhua, Lao [Suzhou Univ., Suzhou (China). Radiation Medicine Department

2001-07-01

HPRT gene locus mutation in peripheral blood lymphocytes induced by internal exposure to radionuclides was performed and the relationships between mutation frequency and dose were studied. Rats were injected intravenously with radionuclides, the blood was sampled at different time after injection; HPRT gene locus mutation frequency (GMF) were examined by methods of multi-nucleus cell and Brdurd assay, working out the Dose-response function. GMF rose with the increase of dose and dose-rates and were clearly interrelated. The HPRT gene locus mutation is very sensitive to radiation and may be used as a biological dosimeter.

A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers

International Nuclear Information System (INIS)

Guinan, Emer M; Hussey, Juliette; McGarrigle, Sarah A; Healy, Laura A; O’Sullivan, Jacintha N; Bennett, Kathleen; Connolly, Elizabeth M

2013-01-01

Breast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. For women who carry the deleterious mutation in either of the BRCA genes, BRCA1 or BRCA2, the risk of developing breast or ovarian cancer is significantly increased. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. The influence of obesity-related biomarkers, which may explain the link between obesity, physical activity and breast cancer risk, has not been investigated prospectively in this group. This paper describes the design of a prospective cohort study investigating the role of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene mutation carriers. Participants will be recruited from breast cancer family risk clinics and genetics clinics. Lifestyle risk factors that will be investigated will include body composition, metabolic syndrome and its components, physical activity and dietary intake. PBMC telomere length will be measured as a potential predictor of breast cancer occurrence. Measurements will be completed on entry to the study and repeated at two years and five years. Participants will also be followed annually by questionnaire to track changes in risk factor status and to record cancer occurrence. Data will be analysed using multiple regression models. The study has an accrual target of 352 participants. The results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene. Additionally, the study will attempt to identify potential blood biomarkers which may be predictive

Gene methylation parallelisms between peripheral blood cells and oral mucosa samples in relation to overweight.

Science.gov (United States)

San-Cristobal, Rodrigo; Navas-Carretero, Santiago; Milagro, Fermín I; Riezu-Boj, J Ignacio; Guruceaga, Elizabeth; Celis-Morales, Carlos; Livingstone, Katherine M; Brennan, Lorraine; Lovegrove, Julie A; Daniel, Hannelore; Saris, Wim H; Traczyk, Iwonna; Manios, Yannis; Gibney, Eileen R; Gibney, Michael J; Mathers, John C; Martinez, J Alfredo

2016-08-01

Epigenetics has an important role in the regulation of metabolic adaptation to environmental modifications. In this sense, the determination of epigenetic changes in non-invasive samples during the development of metabolic diseases could play an important role in the procedures in primary healthcare practice. To help translate the knowledge of epigenetics to public health practice, the present study aims to explore the parallelism of methylation levels between white blood cells and buccal samples in relation to obesity and associated disorders. Blood and buccal swap samples were collected from a subsample of the Spanish cohort of the Food4Me study. Infinium HumanMethylation450 DNA Analysis was carried out for the determination of methylation levels. Standard deviation for β values method and concordance correlation analysis were used to select those CpG which showed best parallelism between samples. A total of 277 CpGs met the criteria and were selected for an enrichment analysis and a correlation analysis with anthropometrical and clinical parameters. From those selected CpGs, four presented high associations with BMI (cg01055691 in GAP43; r = -0.92 and rho = -0.84 for blood; r = -0.89 and rho = -0.83 for buccal sample), HOMA-IR (cg00095677 in ATP2A3; r = 0.82 and rho = -0.84 for blood; r = -0.8 and rho = -0.83 for buccal sample) and leptin (cg14464133 in ADARB2; r = -0.9182 and rho = -0.94 for blood; r = -0.893 and rho = -0.79 for buccal sample). These findings demonstrate the potential application of non-invasive buccal samples in the identification of surrogate epigenetic biomarkers and identify methylation sites in GAP43, ATP2A3 and ADARB2 genes as potential targets in relation to overweight management and insulin sensibility.

Evaluation of Sex-Specific Gene Expression in Archived Dried Blood Spots (DBS

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Scott Jewell

2012-08-01

Full Text Available Screening newborns for treatable serious conditions is mandated in all US states and many other countries. After screening, Guthrie cards with residual blood (whole spots or portions of spots are typically stored at ambient temperature in many facilities. The potential of archived dried blood spots (DBS for at-birth molecular studies in epidemiological and clinical research is substantial. However, it is also challenging as analytes from DBS may be degraded due to preparation and storage conditions. We previously reported an improved assay for obtaining global RNA gene expression from blood spots. Here, we evaluated sex-specific gene expression and its preservation in DBS using oligonucleotide microarray technology. We found X inactivation-specific transcript (XIST, lysine-specific demethylase 5D (KDM5D (also known as selected cDNA on Y, homolog of mouse (SMCY, uncharacterized LOC729444 (LOC729444, and testis-specific transcript, Y-linked 21 (TTTY21 to be differentially-expressed by sex of the newborn. Our finding that trait-specific RNA gene expression is preserved in unfrozen DBS, demonstrates the technical feasibility of performing molecular genetic profiling using such samples. With millions of DBS potentially available for research, we see new opportunities in using newborn molecular gene expression to better understand molecular pathogenesis of perinatal diseases.

Concentration of 12 Metals and Metalloids in the Blood of White Stork (Ciconia ciconia): Basal Values and Influence of Age and Gender.

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Maia, Ana Raquel; Soler-Rodriguez, Francisco; Pérez-López, Marcos

2017-11-01

The white stork (Ciconia ciconia) is being increasingly used in biomonitoring programmes of environmental contaminants due to its growing population in Europe; however, studies on inorganic elements are scarce. The blood of 70 white storks was collected and analysed by inductively coupled plasma mass spectroscopy (ICP-MS) to determine the presence of the following elements: lead (Pb), mercury (Hg), arsenic (As), nickel (Ni), iron (Fe), zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), chromium (Cr), cobalt (Co), and cadmium (Cd). Our main goals were to determine the mean concentrations of these elements in the blood and to study its association with age and gender. Mean concentrations were highest for Fe, followed by Zn, and lowest for Co and Cd. The metal levels were similar to the values referred in the literature for the same species from different locations. No statistically significant differences were found between males and females. Regarding age, statistically significant differences were observed for Ni, Cu, Se, Hg, and Pb between young and adult animals (except for Pb, values in adults were higher than in fledglings). Many element concentrations were correlated, with the strongest correlations between the pairs Hg-Se, Hg-As, and Fe-Zn, mainly in adults. This study provides the baseline data for a monitoring program based on white stork blood as a nondestructive sample.

Differential white cell count by centrifugal microfluidics.

Energy Technology Data Exchange (ETDEWEB)

Sommer, Gregory Jon; Tentori, Augusto M.; Schaff, Ulrich Y.

2010-07-01

We present a method for counting white blood cells that is uniquely compatible with centrifugation based microfluidics. Blood is deposited on top of one or more layers of density media within a microfluidic disk. Spinning the disk causes the cell populations within whole blood to settle through the media, reaching an equilibrium based on the density of each cell type. Separation and fluorescence measurement of cell types stained with a DNA dye is demonstrated using this technique. The integrated signal from bands of fluorescent microspheres is shown to be proportional to their initial concentration in suspension. Among the current generation of medical diagnostics are devices based on the principle of centrifuging a CD sized disk functionalized with microfluidics. These portable 'lab on a disk' devices are capable of conducting multiple assays directly from a blood sample, embodied by platforms developed by Gyros, Samsung, and Abaxis. [1,2] However, no centrifugal platform to date includes a differential white blood cell count, which is an important metric complimentary to diagnostic assays. Measuring the differential white blood cell count (the relative fraction of granulocytes, lymphocytes, and monocytes) is a standard medical diagnostic technique useful for identifying sepsis, leukemia, AIDS, radiation exposure, and a host of other conditions that affect the immune system. Several methods exist for measuring the relative white blood cell count including flow cytometry, electrical impedance, and visual identification from a stained drop of blood under a microscope. However, none of these methods is easily incorporated into a centrifugal microfluidic diagnostic platform.

Novel Applications of Modified Ultrafiltration and Autologous Priming Techniques to Reduce Blood Product Exposure on ECMO.

Science.gov (United States)

Neal, James R; Blau, Caitlin L; Cornelius, Amanda M; Pike, Roxann B; Dearani, Joseph A; Mora, Bassem N

2016-03-01

Patients needing the assistance of extracorporeal membrane oxygenation (ECMO) are at risk of hemodilution and, in some instances, may require exposure to large amounts of allogeneic blood products. Patient outcomes can be improved by taking steps to reduce transfusions and hemodilution. Currently, modified ultrafiltration (MUF) is used across the world to reduce hemodilution after cardiopulmonary bypass (CPB). Another common technique during bypass initiation is autologous priming. By applying modified versions of these techniques, ECMO patients may potentially benefit. Usually, patients requiring immediate transition from CPB to ECMO are not stable enough to tolerate MUF. Through alterations of the CPB and ECMO circuit tubing, MUF can be performed once on ECMO. Another technique to potentially lower the transfusion requirements for ECMO patients is a complete circuit blood transfer during an ECMO circuit exchange. While selective component changes are preferred if possible, occasionally a complete circuit change must be done. To minimize hemodilution or prevent priming with blood products, the original ECMO circuit's blood can be transferred to the new ECMO circuit before connecting to the patient. Both of these techniques, in our opinion, helped to reduce the number of transfusions that our ECMO patients have seen during these critical time periods.

Detection of stx1 and stx2 Genes in Pennsylvanian White-Tailed Deer

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Steven A. Mauro

2011-06-01

Full Text Available Shiga toxin-producing E. coli carrying the stx1 and/or stx2 genes can cause multi-symptomatic illness in humans. A variety of terrestrial and aquatic environmental reservoirs of stx have been described. Culture based detection of microbes in deer species have found a low percentage of samples that have tested positive for Stx-producing microbes, suggesting that while deer may contain these microbes, their overall abundance in deer is low. In this study, quantitative PCR (qPCR was utilized to test for the presence of stx genes in white-tailed deer fecal matter in western Pennsylvania. In this culture independent screening, nearly half of the samples tested positive for the stx2 gene, with a bias towards samples that were concentrated with stx2. This study, while limited in scope, suggests that deer may be a greater reservoir for stx than was previously thought.

Characterization of ORF89 - A latency-related gene of white spot syndrome virus

International Nuclear Information System (INIS)

Hossain, M.S.; Khadijah, Siti; Kwang, Jimmy

2004-01-01

Open reading frame 89 (ORF89) is one of the three genes that are believed to be involved in the latent infection of white spot syndrome virus (WSSV). Here, we report the structure and functional characterization of ORF89. cDNA sequencing, 5' RLM-RACE, and 3' RLM-RACE showed that ORF89 gene is transcribed into an unspliced mRNA of 4436 nucleotides, which is predicted to encode a protein of 1437 amino acids. ORF89 expressed an approximately 165-kDa protein in Sf9 cells that localized in the nucleus. Amino acids 678-683 were found to be essential for nuclear localization. Cotransfection assays demonstrated that ORF89 protein repressed its own promoter as well as those of a protein kinase and the thymidine-thymidylate kinase genes of WSSV. SYBR Green real-time PCR indicated that the repression occurred at the transcriptional level

Tissue- Specific Expression Analysis of Anthocyanin Biosynthetic Genes in White- and Red-Fleshed Grape Cultivars

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Sha Xie

2015-12-01

Full Text Available Yan73, a teinturier (dyer grape variety in China, is one of the few Vitis vinifera cultivars with red-coloured berry flesh. To examine the tissue-specific expression of genes associated with berry colour in Yan73, we analysed the differential accumulation of anthocyanins in the skin and flesh tissues of two red-skinned grape varieties with either red (Yan73 or white flesh (Muscat Hamburg based on HPLC-MS analysis, as well as the differential expression of 18 anthocyanin biosynthesis genes in both varieties by quantitative RT-PCR. The results revealed that the transcripts of GST, OMT, AM3, CHS3, UFGT, MYBA1, F3′5′H, F3H1 and LDOX were barely detectable in the white flesh of Muscat Hamburg. In particular, GST, OMT, AM3, CHS3 and F3H1 showed approximately 50-fold downregulation in the white flesh of Muscat Hamburg compared to the red flesh of Yan73. A correlation analysis between the accumulation of different types of anthocyanins and gene expression indicated that the cumulative expression of GST, F3′5′H, LDOX and MYBA1 was more closely associated with the acylated anthocyanins and the 3′5′-OH anthocyanins, while OMT and AM3 were more closely associated with the total anthocyanins and methoxylated anthocyanins. Therefore, the transcripts of OMT, AM3, GST, F3′5′H, LDOX and MYBA1 explained most of the variation in the amount and composition of anthocyanins in skin and flesh of Yan73. The data suggest that the specific localization of anthocyanins in the flesh tissue of Yan73 is most likely due to the tissue-specific expression of OMT, AM3, GST, F3′5′H, LDOX and MYBA1 in the flesh.

Breeding near a landfill may influence blood metals (Cd, Pb, Hg, Fe, Zn) and metalloids (Se, As) in white stork (Ciconia ciconia) nestlings.

Science.gov (United States)

de la Casa-Resino, Irene; Hernández-Moreno, David; Castellano, Antonio; Pérez-López, Marcos; Soler, Francisco

2014-10-01

Cadmium, lead, mercury, selenium, iron, zinc and arsenic levels were measured in blood samples from 59 free-ranging white stork nestlings from colonies located in three different environmental conditions in Western Spain. The reference colony was situated in "Llanos de Cáceres y Sierra de Fuentes", an Area of Special Interest for Bird Protection. A second colony was located close to (4.9 km) an urban landfill and a third one was close to both an intensive agricultural area and an urban landfill (1.5 km). Blood samples were diluted and elemental analysis was performed using inductively coupled plasma mass spectrometer. In all cases, the essential metals zinc and iron were found at the highest mean concentrations followed by lead > selenium > mercury > arsenic > cadmium. Regarding toxic metals, the highest concentrations were found for lead (ranging from 23.27 to 146.4 µg/L) although in all cases the concentrations were lower than those considered to cause subclinical effects. The metals levels detected in the chick's blood were not related to the previously reported levels in the soil next to the colonies, which may indicate that landfills are the main source of metals in white stork nestlings. The present data showed that metal levels in white stork chicks may be influenced by the use of landfills as feeding areas by the parents. However, more studies on the metal content in the feed of white stork and the influence of the distance to the landfill are necessary to establish the causality of these findings.

Cerebral blood flow and oxygen metabolism in senile dementia of Alzheimer's type and vascular dementia with deep white matter changes

International Nuclear Information System (INIS)

Tohgi, H.; Yonezawa, H.; Takahashi, S.; Sato, N.; Kato, E.; Kudo, M.; Hatano, K.; Sasaki, T.

1998-01-01

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO 2 ), oxygen extraction fraction (rOEF), and cerebral blood volume (rCBV) were investigated using positron emission tomography (PET) in 16 patients with senile dementia of Alzheimer's type (SDAT), and compared with those of 6 nondemented and 3 demented patients with deep white matter high signal (DWMH) on T2-weighted MRI and 6 controls. rCBF, rCMRO 2 and rCBV were determined using C 15 O 2 , 15 O 2 and C 15 O, respectively. rCBF and CMRO 2 were significantly decreased in the frontal, parietal and temporal cortex (P 2 was significantly reduced in only the frontal and temporal cortex of demented patients (P < 0.05). rOEF was significantly increased in the parietal cortex of patients with SDAT and in the white matter of patients with SDAT or DWMH (P < 0.05), and the increase in the frontal white matter significantly paralleled the progression of dementia in patients with SDAT (P < 0.05). rCBV was significantly decreased in the parietal and temporal cortex of patients with SDAT (P < 0.05), but not in any areas of those with DWMH. (orig.)

Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene

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Tosic, Mirjana; Ott, Jurg; Barral, Sandra

2006-01-01

Oxidative stress could be involved in the pathophysiology of schizophrenia, a major psychiatric disorder. Glutathione (GSH), a redox regulator, is decreased in patients' cerebrospinal fluid and prefrontal cortex. The gene of the key GSH-synthesizing enzyme, glutamate cysteine ligase modifier (GCLM......) subunit, is strongly associated with schizophrenia in two case-control studies and in one family study. GCLM gene expression is decreased in patients' fibroblasts. Thus, GSH metabolism dysfunction is proposed as one of the vulnerability factors for schizophrenia....

Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene

DEFF Research Database (Denmark)

Tosic, Mirjana; Ott, Jurg; Barral, Sandra

2006-01-01

Oxidative stress could be involved in the pathophysiology of schizophrenia, a major psychiatric disorder. Glutathione (GSH), a redox regulator, is decreased in patients' cerebrospinal fluid and prefrontal cortex. The gene of the key GSH-synthesizing enzyme, glutamate cysteine ligase modifier (GCL......) subunit, is strongly associated with schizophrenia in two case-control studies and in one family study. GCLM gene expression is decreased in patients' fibroblasts. Thus, GSH metabolism dysfunction is proposed as one of the vulnerability factors for schizophrenia....

A modified method for the in vivo labeling of red blood cells with /sup 99m/Tc: concise communication

International Nuclear Information System (INIS)

Callahan, R.J.; Froelich, J.W.; McKusick, K.A.; Leppo, J.; Strauss, H.W.

1982-01-01

The rate of incorporation of /sup 99m/Tc into red blood cells pretinned in vivo was measured by collecting blood samples in stannous DTPA solution, which served as a competing ligand for /sup 99m/Tc. This collection technique permitted a measurement of high-affinity red-cell labeling efficiency at the instant of sampling. At 0.5 min after injection only 62% of technetium is tightly bound to the red cell; this rises to 94.5% at 10 min. Based on the graded labeling of the red cells, the in vivo labeling procedure was modified by isolating pertechnetate and red blood cells tinned in vivo in a syringe during the first 10 min of labeling. The pertechnetate is thus prevented from distributing to extravascular compartments, and 90% of the injected /sup 99m/Tc is firmly bound to red blood cells at the time of injection. In a series of 23 patients, seven were tested with the in vivo method and seven with the modified in vivo method, and nine patients were tested with each method on separate occasions. A decrease in gastric activity and improved image quality were found with the modified method compared with the standard method of in vivo red-cell labeling

Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

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Desjardins, Stephane; Belkai, Emilie; Crete, Dominique; Cordonnier, Laurie; Scherrmann, Jean-Michel; Noble, Florence; Marie-Claire, Cynthia

2008-12-01

Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, the behavioral signs of spontaneous withdrawal were observed and a withdrawal score was determined. This score enabled to select the time points at which the animals displayed the mildest and strongest withdrawal signs (12 h and 36 h after the last injection). Oligonucleotide arrays were used to assess differential gene expression in the PBMCs and quantitative real-time RT-PCR to validate the modulation of several candidate genes 12 h and 36 h after the last injection. Among the 812 differentially expressed candidates, several genes (Adcy5, Htr2a) and pathways (Map kinases, G-proteins, integrins) have already been described as modulated in the brain of morphine-treated rats. Sixteen out of the twenty-four tested candidates were validated at 12 h, some of them showed a sustained modulation at 36 h while for most of them the modulation evolved as the withdrawal score increased. This study suggests similarities between the gene expression profile in PBMCs and brain of morphine-treated rats. Thus, the searching of correlations between the severity of the withdrawal and the PBMCs gene expression pattern by transcriptional analysis of blood cells could be promising for the study of the mechanisms of addiction.

Modified formulation of CPDA for storage of whole blood, and of SAGM for storage of red blood cells, to maintain the concentration of 2,3-diphosphoglycerate.

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Kurup, P A; Arun, P; Gayathri, N S; Dhanya, C R; Indu, A R

2003-11-01

A dramatic decrease in the level of 2,3-diphosphoglycerate (2,3-DPG) takes place during the storage of whole blood (WB) in CPDA (citrate-phosphate-dextrose-adenine) and a similar decrease occurs during the storage of red blood cells (RBCs) in SAGM (saline-adenine-glucose-mannitol). The aim of the present study was to prevent this decrease by modifying CPDA and SAGM. The pH of WB anticoagulant or RBC preservative solution was maintained at 7.6 by autoclaving the dextrose solution separately, by incorporating ascorbic acid and nicotinic acid into both CPDA and SAGM (to produce modified CPDA and SAGM solutions), and by reducing the concentration of adenine and adding citrate to the modified SAGM solution. The concentration of 2,3-DPG in WB after 28 days of storage in modified CPDA, and in RBCs stored in modified SAGM, was compared with that in WB or RBCs stored in unmodified solutions. The initial 2,3-DPG levels were maintained after 28 days in the modified formulations [10.63 +/- 2.58 microM/g of haemoglobin (Hb) in the case of modified CPDA and 12.07 +/- 1.47 microM/g of Hb in the case of modified SAGM], whereas in standard CPDA and SAGM solutions, the concentration of 2,3-DPG decreased to very low levels (0.86 +/- 0.97 microM/g Hb for CPDA and 0.12 +/- 0.008 for SAGM). Our modification in the formulation of CPDA or SAGM is effective in arresting the dramatic decrease in the level of 2,3-DPG that occurs during storage of WB and RBCs in unmodified solutions.

Application of Ferriferous Oxide Modified by Chitosan in Gene Delivery

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Yu Kuang

2012-01-01

Full Text Available New approaches to improve the traditional gene carriers are still required. Here we explore Fe3O4 modified with degradable polymers that enhances gene delivery and target delivery using permanent magnetic field. Two magnetic Fe3O4 nanoparticles coated with chitosan (CTS and polyethylene glycol (PEG were synthesized by means of controlled chemical coprecipitation. Plasmid pEGFP was encapsulated as a reported gene. The ferriferous oxide complexes were approximately spherical; surface charge of CTS-Fe3O4 and PEG-Fe3O4 was about 20 mv and 0 mv, respectively. The controlled release of DNA from the CTS-Fe3O4 nanoparticles was observed. Concurrently, a desired Fe3O4 concentration of less than 2 mM was verified as safe by means of a cytotoxicity test in vitro. Presence of the permanent magnetic field significantly increased the transfection efficiency. Furthermore, the passive target property and safety of magnetic nanoparticles were also demonstrated in an in vivo test. The novel gene delivery system was proved to be an effective tool required for future target expression and gene therapy in vivo.

Gene Therapy Vectors with Enhanced Transfection Based on Hydrogels Modified with Affinity Peptides

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Shepard, Jaclyn A.; Wesson, Paul J.; Wang, Christine E.; Stevans, Alyson C.; Holland, Samantha J.; Shikanov, Ariella; Grzybowski, Bartosz A.; Shea, Lonnie D.

2011-01-01

Regenerative strategies for damaged tissue aim to present biochemical cues that recruit and direct progenitor cell migration and differentiation. Hydrogels capable of localized gene delivery are being developed to provide a support for tissue growth, and as a versatile method to induce the expression of inductive proteins; however, the duration, level, and localization of expression isoften insufficient for regeneration. We thus investigated the modification of hydrogels with affinity peptides to enhance vector retention and increase transfection within the matrix. PEG hydrogels were modified with lysine-based repeats (K4, K8), which retained approximately 25% more vector than control peptides. Transfection increased 5- to 15-fold with K8 and K4 respectively, over the RDG control peptide. K8- and K4-modified hydrogels bound similar quantities of vector, yet the vector dissociation rate was reduced for K8, suggesting excessive binding that limited transfection. These hydrogels were subsequently applied to an in vitro co-culture model to induce NGF expression and promote neurite outgrowth. K4-modified hydrogels promoted maximal neurite outgrowth, likely due to retention of both the vector and the NGF. Thus, hydrogels modified with affinity peptides enhanced vector retention and increased gene delivery, and these hydrogels may provide a versatile scaffold for numerous regenerative medicine applications. PMID:21514659

Efficacy of double-stranded RNA against white spot syndrome virus (WSSV non-structural (orf89, wsv191 and structural (vp28, vp26 genes in the Pacific white shrimp Litopenaeus vannamei

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César M. Escobedo-Bonilla

2015-04-01

Full Text Available White spot syndrome virus (WSSV is a major pathogen in shrimp aquaculture. RNA interference (RNAi is a promising tool against viral infections. Previous works with RNAi showed different antiviral efficacies depending on the silenced gene. This work evaluated the antiviral efficacy of double-stranded (ds RNA against two non-structural (orf89, wsv191 WSSV genes compared to structural (vp26, vp28 genes to inhibit an experimental WSSV infection. Gene orf89 encodes a putative regulatory protein and gene white spot virus (wsv191 encodes a nonspecific nuclease; whereas genes vp26 and vp28 encode envelope proteins, respectively. Molecules of dsRNA against each of the WSSV genes were intramuscularly injected (4 μg per shrimp into a group of shrimp 48 h before a WSSV challenge. The highest antiviral activity occurred with dsRNA against orf89, vp28 and vp26 (cumulative mortalities 10%, 10% and 21%, respectively. In contrast, the least effective treatment was wsv191 dsRNA (cumulative mortality 83%. All dead animals were WSSV-positive by one-step PCR, whereas reverse-transcription PCR of all surviving shrimp confirmed inhibition of virus replication. This study showed that dsRNA against WSSV genes orf89, vp28 and vp26 were highly effective to inhibit virus replication and suggest an essential role in WSSV infection. Non-structural WSSV genes such as orf89 can be used as novel targets to design therapeutic RNAi molecules against WSSV infection.

Value of black blood T2* cardiovascular magnetic resonance

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Carpenter John Paul

2011-03-01

Full Text Available Abstract Purpose To assess whether black blood T2* cardiovascular magnetic resonance is superior to conventional white blood imaging of cardiac iron in patients with thalassaemia major (TM. Materials and methods We performed both conventional white blood and black blood T2* CMR sequences in 100 TM patients to determine intra and inter-observer variability and presence of artefacts. In 23 patients, 2 separate studies of both techniques were performed to assess interstudy reproducibility. Results Cardiac T2* values ranged from 4.5 to 43.8 ms. The mean T2* values were not different between black blood and white blood acquisitions (20.5 vs 21.6 ms, p = 0.26. Compared with the conventional white blood diastolic acquisition, the coefficient of variance of the black blood CMR technique was superior for intra-observer reproducibility (1.47% vs 4.23%, p Conclusions Black blood T2* CMR has superior reproducibility and reduced imaging artefacts for the assessment of cardiac iron, in comparison with the conventional white blood technique, which make it the preferred technique for clinical practice.

Fast and robust segmentation of white blood cell images by self-supervised learning.

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Zheng, Xin; Wang, Yong; Wang, Guoyou; Liu, Jianguo

2018-04-01

A fast and accurate white blood cell (WBC) segmentation remains a challenging task, as different WBCs vary significantly in color and shape due to cell type differences, staining technique variations and the adhesion between the WBC and red blood cells. In this paper, a self-supervised learning approach, consisting of unsupervised initial segmentation and supervised segmentation refinement, is presented. The first module extracts the overall foreground region from the cell image by K-means clustering, and then generates a coarse WBC region by touching-cell splitting based on concavity analysis. The second module further uses the coarse segmentation result of the first module as automatic labels to actively train a support vector machine (SVM) classifier. Then, the trained SVM classifier is further used to classify each pixel of the image and achieve a more accurate segmentation result. To improve its segmentation accuracy, median color features representing the topological structure and a new weak edge enhancement operator (WEEO) handling fuzzy boundary are introduced. To further reduce its time cost, an efficient cluster sampling strategy is also proposed. We tested the proposed approach with two blood cell image datasets obtained under various imaging and staining conditions. The experiment results show that our approach has a superior performance of accuracy and time cost on both datasets. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of musculoskeletal sepsis with indium-111 white blood cell imaging

International Nuclear Information System (INIS)

Ouzounian, T.J.; Thompson, L.; Grogan, T.J.; Webber, M.M.; Amstutz, H.C.

1987-01-01

The detection of musculoskeletal sepsis, especially following joint replacement, continues to be a challenging problem. Often, even with invasive diagnostic evaluation, the diagnosis of infection remains uncertain. This is a report on the first 55 Indium-111 white blood cell (WBC) images performed in 39 patients for the evaluation of musculoskeletal sepsis. There were 40 negative and 15 positive Indium-111 WBC images. These were correlated with operative culture and tissue pathology, aspiration culture, and clinical findings. Thirty-eight images were performed for the evaluation of possible total joint sepsis (8 positive and 30 negative images); 17 for the evaluation of nonarthroplasty-related musculoskeletal sepsis (7 positive and 10 negative images). Overall, there were 13 true-positive, 39 true-negative, two false-positive, and one false-negative images. Indium-111 WBC imaging is a sensitive and specific means of evaluating musculoskeletal sepsis, especially following total joint replacement

Sex, Adiposity, and Hypertension Status Modify the Inverse Effect of Marine Food Intake on Blood Pressure in Alaska Native (Yup'ik) People.

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Beaulieu-Jones, Brendin R; O'Brien, Diane M; Hopkins, Scarlett E; Moore, Jason H; Boyer, Bert B; Gilbert-Diamond, Diane

2015-05-01

Alaska Native people currently have a higher prevalence of hypertension than do nonnative Alaskans, although in the 1950s hypertension was rare among Alaska Native people. A novel biomarker of marine foods, the nitrogen isotope ratio (δ¹⁵N) in RBCs was shown to be negatively associated with systolic and diastolic blood pressure. Few studies have examined how individual characteristics modify the association of marine food intake with blood pressure. This exploratory analysis examined whether sex, adiposity, and hypertension modify the inverse association between marine food intake and blood pressure. We used covariate-adjusted linear models to describe the association between δ¹⁵N and blood pressure in 873 adult Alaska Native (Yup'ik) people who resided in 8 communities in southwest Alaska. We separately stratified by sex, body mass index (BMI) group, abdominal obesity, and hypertension status and assessed the interaction between δ¹⁵N and participant characteristics on blood pressure via likelihood ratio tests. The association between δ¹⁵N and systolic blood pressure was modified by sex, BMI status, and abdominal obesity, with the inverse association observed only in the male (β = -1.5; 95% CI: -2.4, -0.6 : , nonobese BMI (β = -1.7; 95% CI: -2.5, -1.0), and non-abdominally obese (β = -1.6; 95% CI: -2.4, -0.9) strata (all P-interaction blood pressure associated with δ¹⁵N was observed in the nonobese BMI (β = -1.1; 95% CI: -1.7, -0.5) and non-abdominally obese (β = -1.1; 95% CI: -1.7, -0.5) strata, although only the interaction between BMI group and δ¹⁵N with diastolic blood pressure was significant. The inverse association between δ¹⁵N and both systolic and diastolic blood pressure was observed in nonhypertensive individuals, although the comparison had limited power. The results were consistent with those identified by using combined RBC concentrations of eicosapentaenoic acid and docosahexaenoic acid as the biomarker of marine food

Effect of white striping myopathy on breast muscle (Pectoralis major) protein turnover and gene expression in broilers.

Science.gov (United States)

Vignale, Karen; Caldas, Justina V; England, Judy A; Boonsinchai, Nirun; Magnuson, Andrew; Pollock, Erik D; Dridi, Sami; Owens, Casey M; Coon, Craig N

2017-04-01

A study was conducted to evaluate the effect of white striping ( ) of broiler breast muscle ( Pectoralis major ) on protein turnover and gene expression of genes related to protein degradation and fatty acid synthesis. A total of 560 day-old male broiler chicks Cobb 500 were allocated in a total of 16 pens, 35 chicks per pen. A completely randomized design was conducted with a 2 × 3 factorial arrangement (2 scores: severe and normal, and 3 breast meat samples sites). At d 60, 20 birds were randomly selected, euthanized, and scored for white striping. Scoring was either normal ( , no WS) or severe ( ). Also, the same day, 17 birds (16 infused, one control) were randomly selected and infused with a solution of 15 N Phen 40% ( ). Breast muscle tissue was taken for gene expression analysis of the following genes: MuRF1, atrogin-1, IGF-1, insulin receptor ( ), fatty acid synthetase, and acetyl CoA carboxylase ( ). Each bird was humanely euthanized after 10 minutes of infusion and scored for WS (NORM or SEV). Samples of the breast muscle ( Pectoralis major ) were taken at different layers (3 samples per bird: ventral, medial, dorsal), along with a sample of excreta for 3-methylhistidine analysis. Out of the 16 breast samples taken, only 10 were selected for analysis based on the WS score (5 NORM and 5 SEV). No significant differences ( P > 0.05) were found in fractional synthesis rate ( ) between SEV WS, NORM and sample sites for breast meat. However, fractional breakdown rate ( ) was significantly higher in birds with SEV WS compared to NORM (8.2 and 4.28, respectively, P white striping are degrading more muscular protein and mobilizing more fat. © 2016 Poultry Science Association Inc.

Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis.

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Tong Zhou

Full Text Available Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ~20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis. Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n = 39 from healthy controls (n = 35, 86% classification accuracy and which served as a molecular signature for complicated sarcoidosis (n = 17. As aberrancies in T cell receptor (TCR signaling, JAK-STAT (JS signaling, and cytokine-cytokine receptor (CCR signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1. In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis.

Combined anti-tumor necrosis factor-α therapy and DMARD therapy in rheumatoid arthritis patients reduces inflammatory gene expression in whole blood compared to DMARD therapy alone

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Carl K Edwards

2012-12-01

Full Text Available Periodic assessment of gene expression for diagnosis and monitoring in rheumatoid arthritis (RA may provide a readily available and useful method to detect subclinical disease progression and follow responses to therapy with disease modifying anti-rheumatic agents (DMARDs or anti-TNF-α therapy. We used quantitative real-time PCR to compare peripheral blood gene expression profiles in active ("unstable" RA patients on DMARDs, stable RA patients on DMARDs, and stable RA patients treated with a combination of a DMARD and an anti-TNF-α agent (infliximab or etanercept to healthy human controls. The expression of 48 inflammatory genes were compared between healthy controls (N=122, unstable DMARD patients (N=18, stable DMARD patients (N=26, and stable patients on combination therapy (N=20. Expression of 13 genes was very low or undetectable in all study groups. Compared to healthy controls, patients with unstable RA on DMARDs exhibited increased expression of 25 genes, stable DMARD patients exhibited increased expression of 14 genes and decreased expression of five genes, and combined therapy patients exhibited increased expression of six genes and decreased expression of 10 genes. These findings demonstrate that active RA is associated with increased expression of circulating inflammatory markers whereas increases in inflammatory gene expression are diminished in patients with stable disease on either DMARD or anti-TNF-α therapy. Furthermore, combination DMARD and anti-TNF-α therapy is associated with greater reductions in circulating inflammatory gene expression compared to DMARD therapy alone. These results suggest that assessment of peripheral blood gene expression may prove useful to monitor disease progression and response to therapy.

Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

DEFF Research Database (Denmark)

Basse, Astrid L.; Dixen, Karen; Yadav, Rachita

2015-01-01

abundance and down-regulation of gene expression related to mitochondrial function and oxidative phosphorylation. Global gene expression profiling demonstrated that the time points grouped into three phases: a brown adipose phase, a transition phase and a white adipose phase. Between the brown adipose...

RECRUITMENT OF PATIENTS WITH HEREDITARY HAEMOCHROMATOSIS AS BLOOD DONORS

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Marko Cukjati

2004-12-01

Full Text Available Background. Hereditary haemochromatosis is the most common inherited disorder in white persons with prevalence of about 1 in 200. Therapeutic phlebotomy is an effective treatment for the disease and prevents its sequele. In addition to their altruism, patients with hereditary haemochromatosis have also medical and monetary incentives for blood donation. Current guidelines do not allow haemochromatosis patients to donate blood. About two thirds of patients are eligible as blood donors and about two thirds of therapeutically drawn blood is suitable for transfusion. Therapeutically drawn blood could increase the blood supply by 1.5 to 30%.Conclusions. The number of states that already accept patients with hereditary haemochromatosis as blood donors is increasing. To avoid monetary incentives they offer free phlebotomies for all patients with hereditary haemochromatosis. There have been no reports about higher incidence of transfusion reactions. In Slovenia the number of therapeutic phlebotomy is increasing. We should evaluate the possibilities for recruitment of haemochromatosis patients as blood donors also in our country. It is necessary to modify regulatory restrictions and to ensure that there is no other incentives than altruism for blood donation.

Association of Polymorphisms of Genes Involved in Lipid Metabolism with Blood Pressure and Lipid Values in Mexican Hypertensive Individuals

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Blanca Estela Ríos-González

2014-01-01

Full Text Available Hypertension and dyslipidemia exhibit an important clinical relationship because an increase in blood lipids yields an increase in blood pressure (BP. We analyzed the associations of seven polymorphisms of genes involved in lipid metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC rs1800588, LPL rs328, and MTTP rs1800591 with blood pressure and lipid values in Mexican hypertensive (HT patients. A total of 160 HT patients and 160 normotensive individuals were included. Genotyping was performed through PCR-RFLP, PCR-AIRS, and sequencing. The results showed significant associations in the HT group and HT subgroups classified as normolipemic and hyperlipemic. The alleles FABP2 p.55T, LIPC −514T, and MTTP −493T were associated with elevated systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T were associated with decreased total cholesterol and LDL-C, respectively; APOA5 p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides. The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17–2.93; P=0.001 under the dominant model. These findings indicate that polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and may be important in the development of essential hypertension and dyslipidemia in Mexican HT patients.

Bacterial lipopolysaccharide-induced systemic inflammation alters perfusion of white matter-rich regions without altering flow in brain-irrigating arteries: Relationship to blood-brain barrier breakdown?

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Dhaya, Ibtihel; Griton, Marion; Raffard, Gérard; Amri, Mohamed; Hiba, Bassem; Konsman, Jan Pieter

2018-01-15

To better understand brain dysfunction during sepsis, cerebral arterial blood flow was assessed with Phase Contrast Magnetic Resonance Imaging, perfusion with Arterial Spin Labeling and structure with diffusion-weighted Magnetic Resonance Imaging in rats after intraperitoneal administration of bacterial lipopolysaccharides. Although cerebral arterial flow was not altered, perfusion of the corpus callosum region and diffusion parallel to its fibers were higher after lipopolysaccharide administration as compared to saline injection. In parallel, lipopolysaccharide induced perivascular immunoglobulin-immunoreactivity in white matter. These findings indicate that systemic inflammation can result in increased perfusion, blood-brain barrier breakdown and altered water diffusion in white matter. Copyright © 2017 Elsevier B.V. All rights reserved.

Alternative Splicing and Tissue-specific Elastin Misassembly Act as Biological Modifiers of Human Elastin Gene Frameshift Mutations Associated with Dominant Cutis Laxa*

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Sugitani, Hideki; Hirano, Eiichi; Knutsen, Russell H.; Shifren, Adrian; Wagenseil, Jessica E.; Ciliberto, Christopher; Kozel, Beth A.; Urban, Zsolt; Davis, Elaine C.; Broekelmann, Thomas J.; Mecham, Robert P.

2012-01-01

Elastin is the extracellular matrix protein in vertebrates that provides elastic recoil to blood vessels, the lung, and skin. Because the elastin gene has undergone significant changes in the primate lineage, modeling elastin diseases in non-human animals can be problematic. To investigate the pathophysiology underlying a class of elastin gene mutations leading to autosomal dominant cutis laxa, we engineered a cutis laxa mutation (single base deletion) into the human elastin gene contained in a bacterial artificial chromosome. When expressed as a transgene in mice, mutant elastin was incorporated into elastic fibers in the skin and lung with adverse effects on tissue function. In contrast, only low levels of mutant protein incorporated into aortic elastin, which explains why the vasculature is relatively unaffected in this disease. RNA stability studies found that alternative exon splicing acts as a modifier of disease severity by influencing the spectrum of mutant transcripts that survive nonsense-mediated decay. Our results confirm the critical role of the C-terminal region of tropoelastin in elastic fiber assembly and suggest tissue-specific differences in the elastin assembly pathway. PMID:22573328

Colonic vascular conductance increased by Daikenchuto via calcitonin gene-related peptide and receptor-activity modifying protein 1.

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Kono, Toru; Koseki, Takashi; Chiba, Shinichi; Ebisawa, Yoshiaki; Chisato, Naoyuki; Iwamoto, Jun; Kasai, Shinichi

2008-11-01

Daikencyuto (DKT) is a traditional Japanese medicine (Kampo) and is a mixture of extract powders from dried Japanese pepper, processed ginger, ginseng radix, and maltose powder and has been used as the treatment of paralytic ileus. DKT may increase gastrointestinal motility by an up-regulation of the calcitonin gene-related peptide (CGRP). CGRP is also the most powerful vasoactive substance. In the present study, we investigated whether DKT has any effect on the colonic blood flow in rats. Experiments were performed on fasted anesthetized and artificially ventilated Wistar rats. Systemic mean arterial blood pressure and heart rate were recorded. Red blood cell flux in colonic blood flow was measured using noncontact laser tissue blood flowmetry, and colonic vascular conductance (CVC) was calculated as the ratio of flux to mean arterial blood pressure. We examined four key physiological mechanisms underlying the response using blocker drugs: CGRP1 receptor blocker (CGRP(8-37)), nitric oxide synthase inhibitor, vasoactive intestinal polypeptide (VIP) receptor blocker ([4-Cl-DPhe6, Leu17]-VIP), and substance P receptor blocker (spantide). Reverse transcription-polymerase chain reaction was used for the detection of mRNA of calcitonin receptor-like receptor, receptor-activity modifying protein 1, the component of CGRP 1 receptor and CGRP. After laparotomy, a cannula was inserted into the proximal colon to administer the DKT and to measure CVC at the distal colon. Intracolonal administration of DKT (10, 100, and 300 mg/kg) increased CVC (basal CVC, 0.10 mL/mmHg) from the first 15-min observation period (0.14, 0.17, and 0.17 mL/mmHg, respectively) and with peak response at either 45 min (0.17 mL/mmHg by 10 mg/kg), or 75 and 60 min (0.23 and 0.21 mL/mmHg by 100 and 300 mg/kg, respectively). CGRP(8-37) completely abolished the DKT-induced hyperemia, whereas nitric oxide synthase inhibitor partially attenuated the DKT-induced hyperemia. [4-Cl-DPhe6, Leu17]-VIP and spantide

Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population.

Science.gov (United States)

Asayama, Kei; Thijs, Lutgarde; Li, Yan; Gu, Yu-Mei; Hara, Azusa; Liu, Yan-Ping; Zhang, Zhenyu; Wei, Fang-Fei; Lujambio, Inés; Mena, Luis J; Boggia, José; Hansen, Tine W; Björklund-Bodegård, Kristina; Nomura, Kyoko; Ohkubo, Takayoshi; Jeppesen, Jørgen; Torp-Pedersen, Christian; Dolan, Eamon; Stolarz-Skrzypek, Katarzyna; Malyutina, Sofia; Casiglia, Edoardo; Nikitin, Yuri; Lind, Lars; Luzardo, Leonella; Kawecka-Jaszcz, Kalina; Sandoya, Edgardo; Filipovský, Jan; Maestre, Gladys E; Wang, Jiguang; Imai, Yutaka; Franklin, Stanley S; O'Brien, Eoin; Staessen, Jan A

2014-11-01

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (Pcoat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice. © 2014 American Heart Association, Inc.

Setting Thresholds to Varying Blood Pressure Monitoring Intervals Differentially Affects Risk Estimates Associated With White-Coat and Masked Hypertension in the Population

Science.gov (United States)

Asayama, Kei; Thijs, Lutgarde; Li, Yan; Gu, Yu-Mei; Hara, Azusa; Liu, Yan-Ping; Zhang, Zhenyu; Wei, Fang-Fei; Lujambio, Inés; Mena, Luis J.; Boggia, José; Hansen, Tine W.; Björklund-Bodegård, Kristina; Nomura, Kyoko; Ohkubo, Takayoshi; Jeppesen, Jørgen; Torp-Pedersen, Christian; Dolan, Eamon; Stolarz-Skrzypek, Katarzyna; Malyutina, Sofia; Casiglia, Edoardo; Nikitin, Yuri; Lind, Lars; Luzardo, Leonella; Kawecka-Jaszcz, Kalina; Sandoya, Edgardo; Filipovský, Jan; Maestre, Gladys E.; Wang, Jiguang; Imai, Yutaka; Franklin, Stanley S.; O’Brien, Eoin; Staessen, Jan A.

2015-01-01

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (Phypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice. PMID:25135185

High DNA stability in white blood cells and buffy coat lysates stored at ambient temperature under anoxic and anhydrous atmosphere

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Luis, Aurélie; Colotte, Marthe; Tuffet, Sophie; Bonnet, Jacques

2017-01-01

Conventional storage of blood-derived fractions relies on cold. However, lately, ambient temperature preservation has been evaluated by several independent institutions that see economic and logistic advantages in getting rid of the cold chain. Here we validated a novel procedure for ambient temperature preservation of DNA in white blood cell and buffy coat lysates based on the confinement of the desiccated biospecimens under anoxic and anhydrous atmosphere in original hermetic minicapsules. For this validation we stored encapsulated samples either at ambient temperature or at several elevated temperatures to accelerate aging. We found that DNA extracted from stored samples was of good quality with a yield of extraction as expected. Degradation rates were estimated from the average fragment size of denatured DNA run on agarose gels and from qPCR reactions. At ambient temperature, these rates were too low to be measured but the degradation rate dependence on temperature followed Arrhenius’ law, making it possible to extrapolate degradation rates at 25°C. According to these values, the DNA stored in the encapsulated blood products would remain larger than 20 kb after one century at ambient temperature. At last, qPCR experiments demonstrated the compatibility of extracted DNA with routine DNA downstream analyses. Altogether, these results showed that this novel storage method provides an adequate environment for ambient temperature long term storage of high molecular weight DNA in dehydrated lysates of white blood cells and buffy coats. PMID:29190767

High DNA stability in white blood cells and buffy coat lysates stored at ambient temperature under anoxic and anhydrous atmosphere.

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Anne-Lise Fabre

Full Text Available Conventional storage of blood-derived fractions relies on cold. However, lately, ambient temperature preservation has been evaluated by several independent institutions that see economic and logistic advantages in getting rid of the cold chain. Here we validated a novel procedure for ambient temperature preservation of DNA in white blood cell and buffy coat lysates based on the confinement of the desiccated biospecimens under anoxic and anhydrous atmosphere in original hermetic minicapsules. For this validation we stored encapsulated samples either at ambient temperature or at several elevated temperatures to accelerate aging. We found that DNA extracted from stored samples was of good quality with a yield of extraction as expected. Degradation rates were estimated from the average fragment size of denatured DNA run on agarose gels and from qPCR reactions. At ambient temperature, these rates were too low to be measured but the degradation rate dependence on temperature followed Arrhenius' law, making it possible to extrapolate degradation rates at 25°C. According to these values, the DNA stored in the encapsulated blood products would remain larger than 20 kb after one century at ambient temperature. At last, qPCR experiments demonstrated the compatibility of extracted DNA with routine DNA downstream analyses. Altogether, these results showed that this novel storage method provides an adequate environment for ambient temperature long term storage of high molecular weight DNA in dehydrated lysates of white blood cells and buffy coats.

Transcription of Biotic Stress Associated Genes in White Clover (Trifolium repens L.) Differs in Response to Cyst and Root-Knot Nematode Infection.

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Islam, Afsana; Mercer, Chris F; Leung, Susanna; Dijkwel, Paul P; McManus, Michael T

2015-01-01

The transcription of four members of the Kunitz proteinase inhibitor (KPI) gene family of white clover (Trifolium repens L.), designated as Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5, was investigated at both local infection (roots) and systemic (leaf tissue) sites in white clover in response to infection with the clover root knot nematode (CRKN) Meloidogyne trifoliophila and the clover cyst nematode (CCN) Heterodera trifolii. Invasion by the CRKN resulted in a significant decrease in transcript abundance of Tr-KPI4 locally at both 4 days post-infection (dpi) and at 8 dpi, and an increase in transcription of Tr-KPI1 systemically at 8 dpi. In contrast, an increase in transcript abundance of all four Tr-KPI genes locally at 4 and 8 dpi, and an increase of Tr-KPI1, Tr-KPI2, and Tr-KPI5 at 8 dpi systemically was observed in response to infection with the CCN. Challenge of a resistant (R) genotype and a susceptible (S) genotype of white clover with the CCN revealed a significant increase in transcript abundance of all four Tr-KPI genes locally in the R genotype, while an increase in abundance of only Tr-KPI1, Tr-KPI2, and Tr-KPI5 was observed in the S genotype, and only at 4 dpi. The transcript abundance of a member of the1-AMINOCYCLOPROPANE-1-CARBOXYLATE (ACC) SYNTHASE gene family from white clover (Tr-ACS1) was significantly down-regulated locally in response to CRKN infection at 4 and 8 dpi and at 4 dpi, systemically, while abundance increased locally and systemically at 8 dpi in response to CCN challenge. Conversely, the abundance of the jasmonic acid (JA) signalling gene, CORONATINE-INSENSITIVE PROTEIN 1 from white clover (Tr-COI1) increased significantly at 8 dpi locally in response to CRKN infection, but decreased at 8 dpi in response to CCN infection. The significance of this differential regulation of transcription is discussed with respect to differences in infection strategy of the two nematode species.

Relationship of Hypertension, Blood Pressure, and Blood Pressure Control With White Matter Abnormalities in the Women’s Health Initiative Memory Study (WHIMS)—MRI Trial

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Kuller, Lewis H.; Margolis, Karen L.; Gaussoin, Sarah A.; Bryan, Nick R.; Kerwin, Diana; Limacher, Marian; Wassertheil-Smoller, Sylvia; Williamson, Jeff; Robinson, Jennifer G.

2010-01-01

This paper evaluates the relationship of blood pressure (BP) levels at Women’s Health Initiative (WHI) baseline, treatment of hypertension, and white matter abnormalities among women in conjugated equine estrogen (CEE) and medroxyprogesterone acetate and CEE-alone arms. The WHI Memory Study—Magnetic Resonance Imaging (WHIMS-MRI) trial scanned 1424 participants. BP levels at baseline were significantly positively related to abnormal white matter lesion (WML) volumes. Participants treated for hypertension but who had BP ≥140/90 mm Hg had the greatest amount of WML volumes. Women with untreated BP ≥140/90 mm Hg had intermediate WML volumes. Abnormal WML volumes were related to hypertension in most areas of the brain and were greater in the frontal lobe than in the occipital, parietal, or temporal lobes. Level of BP at baseline was strongly related to amount of WML volumes. The results of the study reinforce the relationship of hypertension and BP control and white matter abnormalities in the brain. The evidence to date supports tight control of BP levels, especially beginning at younger and middle age as a possible and perhaps only way to prevent dementia. PMID:20433539

Visceral Marek's disease in white-peafowl (Pavo cristatus

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G.R. Blume

Full Text Available ABSTRACT Marek's disease (MD is a lymphoproliferative disorder caused by Gallid herpesvirus 2 (MDV that infects mainly domestic gallinaceous birds although wild birds may occasionally be affected. The current report describes the anatomopathological and molecular findings of a case of MD in a white-peafowl (Pavo cristatus. The signs included apathy, hyporexia, and diarrhea. Grossly, 0.5 to 1.5cm in diameter, yellow, soft nodules were observed in the skeletal muscle, lung, kidney, air sacs, small intestine, heart, ovary, ventriculus, and proventriculus. Microscopically, numerous atypical round neoplastic cells were noted. The molecular detection of MDV DNA was implemented to amplify part of the meq gene and products were sequenced for the phylogenetic analysis. Template DNA was obtained from tissues of the affected bird and from blood of all the gallinaceous birds of the Zoo. The expected amplicon for the partial amplification of MDV meq gene was obtained and the amplicons were sequenced. Sequences obtained enabled grouping the strain (accession no. KT768121 with MDV serotype 1 strains from the GenBank. Based on the anatomopathological and molecular findings, the diagnosis of MD in a white-peafowl was reached, and to the authors' knowledge, no previous report regarding MD was published in Pavo cristatus.

Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles.

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Raquel Pinho

Full Text Available The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson's disease (PD progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression

A meta-analysis of gene expression signatures of blood pressure and hypertension.

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Tianxiao Huan

2015-03-01

Full Text Available Genome-wide association studies (GWAS have uncovered numerous genetic variants (SNPs that are associated with blood pressure (BP. Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05. Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%-9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2. Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.

Raman tweezers spectroscopy of live, single red and white blood cells.

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Aseefhali Bankapur

Full Text Available An optical trap has been combined with a Raman spectrometer to make high-resolution measurements of Raman spectra of optically-immobilized, single, live red (RBC and white blood cells (WBC under physiological conditions. Tightly-focused, near infrared wavelength light (1064 nm is utilized for trapping of single cells and 785 nm light is used for Raman excitation at low levels of incident power (few mW. Raman spectra of RBC recorded using this high-sensitivity, dual-wavelength apparatus has enabled identification of several additional lines; the hitherto-unreported lines originate purely from hemoglobin molecules. Raman spectra of single granulocytes and lymphocytes are interpreted on the basis of standard protein and nucleic acid vibrational spectroscopy data. The richness of the measured spectrum illustrates that Raman studies of live cells in suspension are more informative than conventional micro-Raman studies where the cells are chemically bound to a glass cover slip.

Taurine Transporter Gene Expression in Mononuclear Blood Cells of Type 1 Diabetes Patients.

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Napoli, Zaleida; Seghieri, Giuseppe; Bianchi, Loria; Anichini, Roberto; De Bellis, Alessandra; Campesi, Ilaria; Carru, Ciriaco; Occhioni, Stefano; Zinellu, Angelo; Franconi, Flavia

2016-01-01

Taurine transporter gene expression (RNA-TauT) has a role in retinal cell function and is modulated in vitro and in vivo by hyperglycemia and/or oxidative stress. This study was aimed at testing whether RNA-TauT gene expression is modified in blood mononuclear peripheral cells (MPCs) of type 1 diabetic patients, is related to plasma markers of oxidative stress or endothelial dysfunction, or, finally, is related to presence of retinopathy. RNA-TauT was measured in MPCs by real-time PCR-analysis in 35 type 1 diabetic patients and in 33 age- and sex-matched controls, additionally measuring plasma and cell taurine and markers of oxidative stress and endothelial dysfunction. RNA-TauT, expressed as 2(-ΔΔCt), was significantly higher in MPCs of type 1 diabetic patients than in controls [median (interquartile range): 1.32(0.31) versus 1.00(0.15); P = 0.01]. In diabetic patients RNA-TauT was related to HbA1c (r = 0.42; P = 0.01) and inversely to plasma homocysteine (r = -0.39; P = 0.02) being additionally significantly higher in MPCs of patients without retinopathy [(n = 22); 1.36(0.34)] compared to those with retinopathy [(n = 13); 1.16(0.20)], independently from HbA1c or diabetes duration. RNA-TauT gene expression is significantly upregulated in MPCs of type 1 diabetes patients and is related to HbA1c levels and inversely to plasma homocysteine. Finally, in diabetes patients, RNA-TauT upregulation seems to be blunted in patients with retinopathy independently of their metabolic control or longer diabetes duration.

Investigation on Possibility of Transferring OysterMushroom (Pleurotusostreatus Manganese Peroxidase Gene (mnp to the White Button Mushroom (Agaricusbisporus

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Mojgan Parvandi

2017-12-01

Full Text Available Introduction: The white button mushroom does not produce remarkable yield in the third flash. Nutritional deficiency and the inability of this mushroom to efficient use of compost are mentioned as its reasons. Basically, compost includes two major food components, lignocellulose and microbial biomass. But this microbial biomass provides just 10% of button mushroom food needs. According to research studies, differentenzymes in both white button mushroom and oyster mushroom are responsible for decomposition of lignin compounds in compost media, from begin of mycelium grows to the end of fruiting. Lacasse, manganese peroxidase, lignin peroxidase, glyoxal oxidase enzymes contribute to degradation of lignin compounds in degradation mushroom has proven by researchers however itis dependent on mushroom types. Manganese peroxidase enzyme (EC. 1.11.1.13 is an extracellular parser lignin enzyme that has a central peroxidase core. Manganese peroxidase enzyme oxidizesMn2+ to Mn3+ and then Mn3+ oxidizes phenolic structure to fonoxile radical. Produced Mn3+ is very active and makes complex by chelating organic acids that is produced by mushrooms such as oxalate or malate. Mn3+ ions become stable by helping of these chelates and it can penetrate through materials such as wood. On the other hand, in recent years, plant biotechnology provides new solutions for old problems such as use of microorganisms, particularly using bacteria for gene transfer and improvement of superlatives. For a sample of this method, Agrobacterium-mediated transformation system can be noted. In addition, the use of suitable promoters for heterologous genes expression in suitable hosts is an important strategy in functional biotechnology that has been raised in edible mushroom genetic engineering. The lack of efficient and sufficient use of compost, low power of white button mushroom in competition with other rivals, lack of yield per area unit due to production costs, pests and diseases

Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.

Science.gov (United States)

Wagner, Sylvia; Zensi, Anja; Wien, Sascha L; Tschickardt, Sabrina E; Maier, Wladislaw; Vogel, Tikva; Worek, Franz; Pietrzik, Claus U; Kreuter, Jörg; von Briesen, Hagen

2012-01-01

The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.

Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.

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Sylvia Wagner

Full Text Available BACKGROUND: The blood-brain barrier (BBB represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytometry and confocal laser scanning microscopy. Furthermore, different in vitro co-incubation experiments were performed with competing ligands of the respective receptor. CONCLUSIONS/SIGNIFICANCE: This study confirms an active endocytotic uptake mechanism and shows the involvement of low density lipoprotein receptor family members, notably the low density lipoprotein receptor related protein, on the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells. This knowledge of the uptake mechanism of ApoE-modified nanoparticles enables future developments to rationally create very specific and effective carriers to overcome the blood-brain barrier.

The Cardiovascular Risk of White-Coat Hypertension

DEFF Research Database (Denmark)

Franklin, Stanley; Thijs, Lutgarde; Asayama, Kei

2016-01-01

BACKGROUND: The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood. OBJECTIVES: Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring...... in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects. METHODS: European Society Hypertension guidelines were used as a 5-stage risk score...

Saponin, an inhibitory agent of carbon dioxide production by white cells : its use in the microbiologic examination of blood components in an automated bacterial culture system

NARCIS (Netherlands)

van Doorne, Hans; van der Tuuk Adriani, W.P A; van der Ven, L.I; Bosch, E.H; de Natris, T; Smit Sibinga, C.Th.

1998-01-01

BACKGROUND: Blood components with a white cell count >100 x 10(9) per L may cause false-positive results when the BacT/Alert system is used for the microbiologic examination. The effects of different concentrations of saponin on bacterial growth and on carbon dioxide production by blood fractions

Geographical, environmental and pathophysiological influences on the human blood transcriptome.

Science.gov (United States)

Tabassum, Rubina; Nath, Artika; Preininger, Marcela; Gibson, Greg

2013-12-01

Gene expression variation provides a read-out of both genetic and environmental influences on gene activity. Geographical, genomic and sociogenomic studies have highlighted how life circumstances of an individual modify the expression of hundreds and in some cases thousands of genes in a co-ordinated manner. This review places such results in the context of a conserved set of 90 transcripts known as Blood Informative Transcripts (BIT) that capture the major conserved components of variation in the peripheral blood transcriptome. Pathophysiological states are also shown to associate with the perturbation of transcript abundance along the major axes. Discussion of false negative rates leads us to argue that simple significance thresholds provide a biased perspective on assessment of differential expression that may cloud the interpretation of studies with small sample sizes.

Generation of CMAHKO/GTKO/shTNFRI-Fc/HO-1 quadruple gene modified pigs.

Science.gov (United States)

Kim, Geon A; Lee, Eun Mi; Jin, Jun-Xue; Lee, Sanghoon; Taweechaipaisankul, Anukul; Hwang, Jong Ik; Alam, Zahid; Ahn, Curie; Lee, Byeong Chun

2017-08-01

As an alternative source of organs for transplantation into humans, attention has been directed to pigs due to their similarities in biological features and organ size. However, severe immune rejection has prevented successful xenotransplantation using pig organs and tissues. To overcome immune rejection, recently developed genetic engineering systems such as TALEN coupled with somatic cell nuclear transfer (SCNT) to make embryos could be used to produce pigs compatible with xenotransplantation. We used the TALEN system to target the non-Gal antigen cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene in pigs that is naturally deleted in humans. Gal-deleted cells expressing both soluble human tumor necrosis factor receptor I IgG 1 -Fc (shTNFRI-Fc) and human hemagglutinin -tagged-human heme oxygenase-1 (hHO-1) were transfected with a TALEN target for CMAH. Cells lacking CMAH were negatively selected using N-glyconeuraminic acid (Neu5Gc)/magnetic beads and the level of Neu5Gc expression of isolated cells were analyzed by FACS and DNA sequencing. Cloned embryos using 3 different genetically modified cell clones were respectively transferred into 3 recipients, with 55.6% (5/9) becoming pregnant and three cloned pigs were produced. Successful genetic disruption of the CMAH gene was confirmed by sequencing, showing lack of expression of CMAH in tail-derived fibroblasts of the cloned piglets. Besides decreased expression of Neu5Gc in piglets produced by SCNT, antibody-mediated complement-dependent cytotoxicity assays and natural antibody binding for examining immuno-reactivity of the quadruple gene modified pigs derived from endothelial cells and fibroblasts were reduced significantly compared to those of wild type animals. We conclude that by combining the TALEN system and transgenic cells, targeting of multiple genes could be useful for generating organs for xenotransplantation. We produced miniature pigs with quadruple modified genes CMAHKO

Three-generation reproduction toxicity study of genetically modified rice with insect resistant genes.

Science.gov (United States)

Hu, Yichun; Zhuo, Qin; Gong, Zhaolong; Piao, Jianhua; Yang, Xiaoguang

2017-01-01

In the present work, we evaluated the three generation reproductive toxicity of the genetically modified rice with insectresistant cry1Ac and sck genes. 120 Sprague-Dawley (SD) rats were divided into three groups which were fed with genetically modified rice diet (GM group), parental control rice diet (PR group) and AIN-93 control diet (both used as negative control) respectively. Bodyweight, food consumption, reproductive data, hematological parameters, serum chemistry, relative organ weights and histopathology for each generation were examined respectively. All the hematology and serum chemistry parameters, organ/body weight indicators were within the normal range or no change to the adverse direction was observed, although several differences in hematology and serum chemistry parameters (WBC, BUN, LDH of male rat, PLT, PCT, MPV of female rats), reproductive data (rate of morphologically abnormal sperm) were observed between GM rice group and two control groups. No macroscopic or histological adverse effects were found or considered as treatment-related, either. Overall, the three generation study of genetically modified rice with cry1Ac and sck genes at a high level showed no unintended adverse effects on rats's reproductive system. Copyright © 2016. Published by Elsevier Ltd.

Surface characterization and free thyroid hormones response of chemically modified poly(ethylene terephthalate) blood collection tubes

Science.gov (United States)

Jalali Dil, Ebrahim; Kim, Samuel C.; Saffar, Amir; Ajji, Abdellah; Zare, Richard N.; Sattayapiwat, Annie; Esguerra, Vanessa; Bowen, Raffick A. R.

2018-06-01

The surface chemistry and surface energy of chemically modified polyethylene terephthalate (PET) blood collection tubes (BCTs) were studied and the results showed a significant increase in hydrophilicity and polarity of modified PET surface. The surface modification created nanometer-sized, needle-like asperities through molecular segregation at the surface. The surface dynamics of the modified PET was examined by tracking its surface properties over a 280-day period. The results showed surface rearrangement toward a surface with lower surface energy and fewer nanometer-sized asperities. Thromboelastography (TEG) was used to evaluate and compare the thrombogenicity of the inner walls of various types of BCTs. The TEG tracings and data from various types of BCTs demonstrated differences in the reactionand coagulation times but not in clot strength. The performance of the modified tubes in free triiodothyronine (FT3) and free thyroxine (FT4) hormone tests was examined, and it was found that the interference of modified PET tubes was negligible compared to that of commercially available PET BCTs.

Age-associated DNA methylation changes in immune genes, histone modifiers and chromatin remodeling factors within 5 years after birth in human blood leukocytes

DEFF Research Database (Denmark)

Acevedo, Nathalie; Reinius, Lovisa E; Vitezic, Morana

2015-01-01

BACKGROUND: Age-related changes in DNA methylation occurring in blood leukocytes during early childhood may reflect epigenetic maturation. We hypothesized that some of these changes involve gene networks of critical relevance in leukocyte biology and conducted a prospective study to elucidate...... factors (for example, HDAC4, KDM2A, KDM2B, JARID2, ARID3A, and SMARCD3) undergo DNA methylation changes in leukocytes during early childhood. These results open new perspectives to understand leukocyte maturation and provide a catalogue of CpG sites that may need to be corrected for age effects when...... the dynamics of DNA methylation. Serial blood samples were collected at 3, 6, 12, 24, 36, 48 and 60 months after birth in ten healthy girls born in Finland and participating in the Type 1 Diabetes Prediction and Prevention Study. DNA methylation was measured using the HumanMethylation450 BeadChip. RESULTS...

Transferrin-modified liposome promotes α-mangostin to penetrate the blood-brain barrier.

Science.gov (United States)

Chen, Zhi-Lan; Huang, Man; Wang, Xia-Rong; Fu, Jun; Han, Min; Shen, You-Qing; Xia, Zheng; Gao, Jian-Qing

2016-02-01

α-Mangostin (α-M) is a polyphenolic xanthone that protects and improves the survival of cerebral cortical neurons against Aβ oligomer-induced toxicity in rats. α-M is a potential candidate as a treatment for Alzheimer's disease (AD). However, the efficacy was limited by the poor penetration of the drug through the blood-brain barrier (BBB). In this study, we modified the α-M liposome with transferrin (Tf) and investigated the intracellular distribution of liposomes in bEnd3 cells. In addition, the transport of α-M across the BBB in the Tf(α-M) liposome group was examined. In vitro studies demonstrated that the Tf(α-M) liposome could cross the BBB in the form of an integrated liposome. Results of the in vivo studies on the α-M distribution in the brain demonstrated that the Tf(α-M) liposome improved the brain delivery of α-M. These results indicated that the Tf liposome is a potential carrier of α-M against AD. The use of α-Mangostin (α-M) as a potential agent to treat Alzheimer's disease (AD) has been reported. However, its use is limited by the poor penetration through the blood brain barrier. The delivery of this agent by transferrin-modified liposomes was investigated by the authors in this study. The positive results could point to a better drug delivery system for brain targeting. Copyright © 2015 Elsevier Inc. All rights reserved.

Adoptive Immunotherapy for Hematological Malignancies Using T Cells Gene-Modified to Express Tumor Antigen-Specific Receptors

Directory of Open Access Journals (Sweden)

Hiroshi Fujiwara

2014-12-01

Full Text Available Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL for melanoma. Currently, along with advances in synthetic immunology, gene-modified T cells retargeted to defined tumor antigens have been introduced as “cellular drugs”. As the functional properties of the adoptive immune response mediated by T lymphocytes are decisively regulated by their T-cell receptors (TCRs, transfer of genes encoding target antigen-specific receptors should enable polyclonal T cells to be uniformly redirected toward cancer cells. Clinically, anticancer adoptive immunotherapy using genetically engineered T cells has an impressive track record. Notable examples include the dramatic benefit of chimeric antigen receptor (CAR gene-modified T cells redirected towards CD19 in patients with B-cell malignancy, and the encouraging results obtained with TCR gene-modified T cells redirected towards NY-ESO-1, a cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. This article overviews the current status of this treatment option, and discusses challenging issues that still restrain the full effectiveness of this strategy, especially in the context of hematological malignancy.

HFE gene variants modify the association between maternal lead burden and infant birthweight: a prospective birth cohort study in Mexico City, Mexico.

Science.gov (United States)

Cantonwine, David; Hu, Howard; Téllez-Rojo, Martha Maria; Sánchez, Brisa N; Lamadrid-Figueroa, Héctor; Ettinger, Adrienne S; Mercado-García, Adriana; Hernández-Avila, Mauricio; Wright, Robert O

2010-07-26

Neonatal growth is a complex process involving genetic and environmental factors. Polymorphisms in the hemochromatosis (HFE) iron regulatory genes have been shown to modify transport and toxicity of lead which is known to affect birth weight. We investigated the role of HFE C282Y, HFE H63 D, and transferrin (TF) P570 S gene variants in modifying the association of lead and infant birthweight in a cohort of Mexican mother-infant pairs. Subjects were initially recruited between 1994-1995 from three maternity hospitals in Mexico City and 411 infants/565 mothers had archived blood available for genotyping. Multiple linear regression models, stratified by either maternal/infant HFE or TF genotype and then combined with interaction terms, were constructed examining the association of lead and birthweight after controlling for covariates. 3.1%, 16.8% and 17.5% of infants (N=390) and 1.9%, 14.5% and 18.9% of mothers (N=533) carried the HFE C282Y, HFE H63D, and TF P570 S variants, respectively. The presence of infant HFE H63 D variants predicted 110.3 g (95% CI -216.1, -4.6) decreases in birthweight while maternal HFE H63 D variants predicted reductions of 52.0 g (95% CI -147.3 to 43.2). Interaction models suggest that both maternal and infant HFE H63 D genotype may modify tibia lead's effect on infant birthweight in opposing ways. In our interaction models, maternal HFE H63 D variant carriers had a negative association between tibia lead and birthweight. These results suggest that the HFE H63 D genotype modifies lead's effects on infant birthweight in a complex fashion that may reflect maternal-fetal interactions with respect to the metabolism and transport of metals.

A genome-wide scan study identifies a single nucleotide substitution in ASIP associated with white versus non-white coat-colour variation in sheep (Ovis aries).

Science.gov (United States)

Li, M-H; Tiirikka, T; Kantanen, J

2014-02-01

In sheep, coat colour (and pattern) is one of the important traits of great biological, economic and social importance. However, the genetics of sheep coat colour has not yet been fully clarified. We conducted a genome-wide association study of sheep coat colours by genotyping 47 303 single-nucleotide polymorphisms (SNPs) in the Finnsheep population in Finland. We identified 35 SNPs associated with all the coat colours studied, which cover genomic regions encompassing three known pigmentation genes (TYRP1, ASIP and MITF) in sheep. Eighteen of these associations were confirmed in further tests between white versus non-white individuals, but none of the 35 associations were significant in the analysis of only non-white colours. Across the tests, the s66432.1 in ASIP showed significant association (P=4.2 × 10(-11) for all the colours; P=2.3 × 10(-11) for white versus non-white colours) with the variation in coat colours and strong linkage disequilibrium with other significant variants surrounding the ASIP gene. The signals detected around the ASIP gene were explained by differences in white versus non-white alleles. Further, a genome scan for selection for white coat pigmentation identified a strong and striking selection signal spanning ASIP. Our study identified the main candidate gene for the coat colour variation between white and non-white as ASIP, an autosomal gene that has been directly implicated in the pathway regulating melanogenesis. Together with ASIP, the two other newly identified genes (TYRP1 and MITF) in the Finnsheep, bordering associated SNPs, represent a new resource for enriching sheep coat-colour genetics and breeding.

Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial.

Directory of Open Access Journals (Sweden)

Arash Hossein-nezhad

Full Text Available Although there have been numerous observations of vitamin D deficiency and its links to chronic diseases, no studies have reported on how vitamin D status and vitamin D3 supplementation affects broad gene expression in humans. The objective of this study was to determine the effect of vitamin D status and subsequent vitamin D supplementation on broad gene expression in healthy adults. (Trial registration: ClinicalTrials.gov NCT01696409.A randomized, double-blind, single center pilot trial was conducted for comparing vitamin D supplementation with either 400 IUs (n = 3 or 2000 IUs (n = 5 vitamin D3 daily for 2 months on broad gene expression in the white blood cells collected from 8 healthy adults in the winter. Microarrays of the 16 buffy coats from eight subjects passed the quality control filters and normalized with the RMA method. Vitamin D3 supplementation that improved serum 25-hydroxyvitamin D concentrations was associated with at least a 1.5 fold alteration in the expression of 291 genes. There was a significant difference in the expression of 66 genes between subjects at baseline with vitamin D deficiency (25(OHD20 ng/ml. After vitamin D3 supplementation gene expression of these 66 genes was similar for both groups. Seventeen vitamin D-regulated genes with new candidate vitamin D response elements including TRIM27, CD83, COPB2, YRNA and CETN3 which have been shown to be important for transcriptional regulation, immune function, response to stress and DNA repair were identified.Our data suggest that any improvement in vitamin D status will significantly affect expression of genes that have a wide variety of biologic functions of more than 160 pathways linked to cancer, autoimmune disorders and cardiovascular disease with have been associated with vitamin D deficiency. This study reveals for the first time molecular finger prints that help explain the nonskeletal health benefits of vitamin D.ClinicalTrials.gov NCT01696409.

Magnetophoretic separation of blood cells at the microscale

International Nuclear Information System (INIS)

Furlani, E P

2007-01-01

We present a method and model for the direct and continuous separation of red and white blood cells in plasma. The method is implemented at the microscale using a microfluidic system that consists of an array of integrated soft-magnetic elements embedded adjacent to a microfluidic channel. The microsystem is passive and is activated via application of a bias field that magnetizes the elements. Once magnetized, the elements produce a nonuniform magnetic field distribution in the microchannel, which gives rise to a force on blood cells as they pass through the microsystem. In whole blood, white blood cells behave as diamagnetic microparticles while red blood cells exhibit diamagnetic or paramagnetic behaviour depending on the oxygenation of their haemoglobin. We develop a mathematical model for predicting the motion of blood cells in the microsystem that takes into account the dominant magnetic, fluidic and buoyant forces on the cells. We use the model to study red/white blood cell transport, and our analysis indicates that the microsystem is capable of rapid and efficient red/white blood cell separation

Dissecting Daily and Circadian Expression Rhythms of Clock-Controlled Genes in Human Blood.

Science.gov (United States)

Lech, Karolina; Ackermann, Katrin; Revell, Victoria L; Lao, Oscar; Skene, Debra J; Kayser, Manfred

2016-02-01

The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study. Statistically significant rhythms in expression were observed for STAT3, SREBF1, TRIB1, and THRA1 in samples from both the S/SD and the CR studies, indicating that their rhythmicity is driven by the endogenous clock. The MKNK2 gene was significantly rhythmic in the S/SD but not the CR study, which implies its exogenously driven rhythmic expression. In addition, we confirmed the circadian expression of PER1, PER3, and REV-ERBα in the CR study samples, while BMAL1 and HSPA1B were not significantly rhythmic in the CR samples; all 5 genes previously showed significant expression in the S/SD study samples. Overall, our results demonstrate that rhythmic expression patterns of clock and selected clock-controlled genes in human blood cells are in part determined by exogenous factors (sleep and fasting state) and in part by the endogenous circadian timing system. Knowledge of the exogenous and endogenous regulation of gene expression rhythms is needed prior to the selection of potential candidate marker genes for future applications in medical and forensic settings. © 2015 The Author(s).

Decoding white coat hypertension

Science.gov (United States)

Bloomfield, Dennis A; Park, Alex

2017-01-01

There is arguably no less understood or more intriguing problem in hypertension that the “white coat” condition, the standard concept of which is significantly blood pressure reading obtained by medical personnel of authoritative standing than that obtained by more junior and less authoritative personnel and by the patients themselves. Using hospital-initiated ambulatory blood pressure monitoring, the while effect manifests as initial and ending pressure elevations, and, in treated patients, a low daytime profile. The effect is essentially systolic. Pure diastolic white coat hypertension appears to be exceedingly rare. On the basis of the studies, we believe that the white coat phenomenon is a common, periodic, neuro-endocrine reflex conditioned by anticipation of having the blood pressure taken and the fear of what this measurement may indicate concerning future illness. It does not change with time, or with prolonged association with the physician, particularly with advancing years, it may be superimposed upon essential hypertension, and in patients receiving hypertensive medication, blunting of the nighttime dip, which occurs in about half the patients, may be a compensatory mechanisms, rather than an indication of cardiovascular risk. Rather than the blunted dip, the morning surge or the widened pulse pressure, cardiovascular risk appears to be related to elevation of the average night time pressure. PMID:28352632

Binding Characteristics Of Ivermectin To Blood Cells | Nweke ...

African Journals Online (AJOL)

The binding characteristics of Ivermectin were determined using scatchard plots. The percentage binding to platelet rich plasma, white blood cells and red blood cells were 90.00 + 1.00, 96-90 + 1.05 and 46.20 + 1.10 S.D respectively. It was found to bind the highest to white blood cells and the least to red blood cells.

Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population

DEFF Research Database (Denmark)

Asayama, Kei; Thijs, Lutgarde; Li, Yan

2014-01-01

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥14...

Sequence-Based Introgression Mapping Identifies Candidate White Mold Tolerance Genes in Common Bean

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Sujan Mamidi

2016-07-01

Full Text Available White mold, caused by the necrotrophic fungus (Lib. de Bary, is a major disease of common bean ( L.. WM7.1 and WM8.3 are two quantitative trait loci (QTL with major effects on tolerance to the pathogen. Advanced backcross populations segregating individually for either of the two QTL, and a recombinant inbred (RI population segregating for both QTL were used to fine map and confirm the genetic location of the QTL. The QTL intervals were physically mapped using the reference common bean genome sequence, and the physical intervals for each QTL were further confirmed by sequence-based introgression mapping. Using whole-genome sequence data from susceptible and tolerant DNA pools, introgressed regions were identified as those with significantly higher numbers of single-nucleotide polymorphisms (SNPs relative to the whole genome. By combining the QTL and SNP data, WM7.1 was located to a 660-kb region that contained 41 gene models on the proximal end of chromosome Pv07, while the WM8.3 introgression was narrowed to a 1.36-Mb region containing 70 gene models. The most polymorphic candidate gene in the WM7.1 region encodes a BEACH-domain protein associated with apoptosis. Within the WM8.3 interval, a receptor-like protein with the potential to recognize pathogen effectors was the most polymorphic gene. The use of gene and sequence-based mapping identified two candidate genes whose putative functions are consistent with the current model of pathogenicity.

Gene flow in genetically modified wheat.

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Silvan Rieben

Full Text Available Understanding gene flow in genetically modified (GM crops is critical to answering questions regarding risk-assessment and the coexistence of GM and non-GM crops. In two field experiments, we tested whether rates of cross-pollination differed between GM and non-GM lines of the predominantly self-pollinating wheat Triticum aestivum. In the first experiment, outcrossing was studied within the field by planting "phytometers" of one line into stands of another line. In the second experiment, outcrossing was studied over distances of 0.5-2.5 m from a central patch of pollen donors to adjacent patches of pollen recipients. Cross-pollination and outcrossing was detected when offspring of a pollen recipient without a particular transgene contained this transgene in heterozygous condition. The GM lines had been produced from the varieties Bobwhite or Frisal and contained Pm3b or chitinase/glucanase transgenes, respectively, in homozygous condition. These transgenes increase plant resistance against pathogenic fungi. Although the overall outcrossing rate in the first experiment was only 3.4%, Bobwhite GM lines containing the Pm3b transgene were six times more likely than non-GM control lines to produce outcrossed offspring. There was additional variation in outcrossing rate among the four GM-lines, presumably due to the different transgene insertion events. Among the pollen donors, the Frisal GM line expressing a chitinase transgene caused more outcrossing than the GM line expressing both a chitinase and a glucanase transgene. In the second experiment, outcrossing after cross-pollination declined from 0.7-0.03% over the test distances of 0.5-2.5 m. Our results suggest that pollen-mediated gene flow between GM and non-GM wheat might only be a concern if it occurs within fields, e.g. due to seed contamination. Methodologically our study demonstrates that outcrossing rates between transgenic and other lines within crops can be assessed using a phytometer

Gene flow in genetically modified wheat.

Science.gov (United States)

Rieben, Silvan; Kalinina, Olena; Schmid, Bernhard; Zeller, Simon L

2011-01-01

Understanding gene flow in genetically modified (GM) crops is critical to answering questions regarding risk-assessment and the coexistence of GM and non-GM crops. In two field experiments, we tested whether rates of cross-pollination differed between GM and non-GM lines of the predominantly self-pollinating wheat Triticum aestivum. In the first experiment, outcrossing was studied within the field by planting "phytometers" of one line into stands of another line. In the second experiment, outcrossing was studied over distances of 0.5-2.5 m from a central patch of pollen donors to adjacent patches of pollen recipients. Cross-pollination and outcrossing was detected when offspring of a pollen recipient without a particular transgene contained this transgene in heterozygous condition. The GM lines had been produced from the varieties Bobwhite or Frisal and contained Pm3b or chitinase/glucanase transgenes, respectively, in homozygous condition. These transgenes increase plant resistance against pathogenic fungi. Although the overall outcrossing rate in the first experiment was only 3.4%, Bobwhite GM lines containing the Pm3b transgene were six times more likely than non-GM control lines to produce outcrossed offspring. There was additional variation in outcrossing rate among the four GM-lines, presumably due to the different transgene insertion events. Among the pollen donors, the Frisal GM line expressing a chitinase transgene caused more outcrossing than the GM line expressing both a chitinase and a glucanase transgene. In the second experiment, outcrossing after cross-pollination declined from 0.7-0.03% over the test distances of 0.5-2.5 m. Our results suggest that pollen-mediated gene flow between GM and non-GM wheat might only be a concern if it occurs within fields, e.g. due to seed contamination. Methodologically our study demonstrates that outcrossing rates between transgenic and other lines within crops can be assessed using a phytometer approach and that gene

Deterministic hydrodynamics: Taking blood apart

Science.gov (United States)

Davis, John A.; Inglis, David W.; Morton, Keith J.; Lawrence, David A.; Huang, Lotien R.; Chou, Stephen Y.; Sturm, James C.; Austin, Robert H.

2006-10-01

We show the fractionation of whole blood components and isolation of blood plasma with no dilution by using a continuous-flow deterministic array that separates blood components by their hydrodynamic size, independent of their mass. We use the technology we developed of deterministic arrays which separate white blood cells, red blood cells, and platelets from blood plasma at flow velocities of 1,000 μm/sec and volume rates up to 1 μl/min. We verified by flow cytometry that an array using focused injection removed 100% of the lymphocytes and monocytes from the main red blood cell and platelet stream. Using a second design, we demonstrated the separation of blood plasma from the blood cells (white, red, and platelets) with virtually no dilution of the plasma and no cellular contamination of the plasma. cells | plasma | separation | microfabrication

Applications of Gene Editing Technologies to Cellular Therapies.

Science.gov (United States)

Rein, Lindsay A M; Yang, Haeyoon; Chao, Nelson J

2018-03-27

Hematologic malignancies are characterized by genetic heterogeneity, making classic gene therapy with a goal of correcting 1 genetic defect ineffective in many of these diseases. Despite initial tribulations, gene therapy, as a field, has grown by leaps and bounds with the recent development of gene editing techniques including zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR) sequences and CRISPR-associated protein-9 (Cas9) nuclease or CRISPR/Cas9. These novel technologies have been applied to efficiently and specifically modify genetic information in target and effector cells. In particular, CRISPR/Cas9 technology has been applied to various hematologic malignancies and has also been used to modify and improve chimeric antigen receptor-modified T cells for the purpose of providing effective cellular therapies. Although gene editing is in its infancy in malignant hematologic diseases, there is much room for growth and application in the future. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Aqueous extract of Telfairia occidentalis leaves reduces blood sugar ...

African Journals Online (AJOL)

STORAGESEVER

2008-07-18

Jul 18, 2008 ... white blood cell counts), sperm parameters (sperm motility, viability and counts) and blood glucose were determined. ... cantly increased red blood cell count, white blood cell count, packed cell volume and .... improve sperm motility and fertility in smokers (Dawson et al., 1992) and boar (Ivos et al., 1971), ...

Pyruvate kinase blood test

Science.gov (United States)

... medlineplus.gov/ency/article/003357.htm Pyruvate kinase blood test To use the sharing features on this page, ... energy when oxygen levels are low. How the Test is Performed A blood sample is needed. In the laboratory, white blood ...

Effects of Onion Extracts on Growth Performance, Carcass Characteristics and Blood Profiles of White Mini Broilers

Directory of Open Access Journals (Sweden)

B. K. An

2015-02-01

Full Text Available This experiment was carried out to investigate effects of onion extract on growth performance, meat quality and blood profiles of White mini broilers. Total of 600 one-d-old male White mini broiler chicks were divided into four groups and fed control diets (non-medicated commercial diet or antibiotics medicated or experimental diets (non-medicated diets containing 0.3% or 0.5% onion extract for 5 wks. The final body weight (BW and weight gain of the group fed non-medicated control diet were lower than those of medicated control group (p<0.01. The chicks fed diet with 0.3% or 0.5% onion extract showed a similar BW to that of medicated control group. The relative weight of various organs, such as liver, spleen, bursa of Fabricius, abdominal fat, and the activities of serum enzymes were not affected by dietary treatments. There were no significant differences in meat color among groups. Whereas, groups fed diets containing onion extract had slightly lower cooking loss and higher shear force value, but not significantly. The concentrations of serum free cholesterol and triacylglycerol in groups fed diet containing onion extract were significantly decreased compared with those of controls (p<0.01. In conclusion, the onion extracts exerted a growth-promoting effect when added in White mini broiler diets, reflecting potential alternative substances to replace antibiotics.

The impact of preapheresis white blood cell count on autologous peripheral blood stem cell collection efficiency and HSC infusion side effect rate.

Science.gov (United States)

Sakashita, Araci M; Kondo, Andrea T; Yokoyama, Ana Paula H; Lira, Sanny M C; Bub, Carolina B; Souza, Aline M; Cipolletta, Andrea N F; Alvarez, Kelen C; Hamerschlak, Nelson; Kutner, Jose M; Chiattone, Carlos S

2018-01-19

Autologous peripheral blood hematopoietic stem cell (PBSC) collection efficiency (CE) is reportedly affected by the patient's blood properties; however, studies to identify factors correlated with CE have shown inconsistent results. Additionally, variables such as stem cell graft granulocyte content and patient age, sex, and underlying disease, may be associated with hematopietic stem cell (HSC) infusion-related adverse reactions. In this study, we evaluated the correlation of preleukapheresis PB granulocyte count and PBSC harvest variables with CD34 + collection yield and efficiency, and thawed HSC infusion side effect occurrence. We evaluated data from 361 patients who had undergone autologous PBSC transplant. Large volume leukapheresis was the method for PBSC collection. Complete Blood Count and CD34 + cell enumeration were performed in the preapheresis PB and the apheresis product sample. The PBSC grafts were submitted to non-controlled rate freezing after addition of 5% DMSO plus 6% hidroxyethylstarch as a cryoprotectant solution. The cryopreserved graft was thawed in a 37°C water bath and then infused without further manipulation. The CD34 + yield was associated with preapheresis PB CD34 + count and immature granulocyte count. The PBSC CE was negatively correlated with preapheresis white blood cell (WBC), immature granulocyte and granulocyte count. The leukapheresis product total nucleated cell (TNC) and granulocyte content was correlated with the thawed graft infusion side effect occurrence. This study has shown that preapheresis PB WBC and granulocyte counts were associated with leukapheresis CE. Additionally, the leukapheresis product TNC and granulocyte content was correlated with thawed graft infusion side effect occurrence. © 2018 Wiley Periodicals, Inc.

Separation of breast cancer cells from peripherally circulating blood using antibodies fixed in microchannels

Science.gov (United States)

Feng, Juan; Soper, Steven A.; McCarley, Robin L.; Murphy, Michael C.

2004-07-01

Bio-Micro Electro Mechanical System (Bio-MEMS) technology was applied to the problem of early breast cancer detection and diagnosis. A micro-device is being developed to identify and specifically collect tumor cells of low abundance (1 tumor cell among 107 normal blood cells) from circulating whole blood. By immobilizing anti-EpCAM (Epithelial Cell Adhesion Molecule) antibodies on polymer micro-channel walls by chemically modifying the surface of the PMMA, breast cancer cells from the MCF-7 cell line, which over-express EpCAM, were selected from a sample volume by the strong binding affinity between the antibody and antigen. To validate the capture of the breast cancer cells, three fluorochrome markers, each identified by a separate color, were used to reliably identify the cancer cells. The cancer cells were defined by DAPI+ (blue), CD45- and the FITC-cell membrane linker+ (green). White blood cells, which may interfere in the detection of the cancer cells, were identified by DAPI+ (blue), CD45+ (red), and the FITC-cell membrane linker+ (green). EpCAM/anti-EpCAM binding models from the literature were used to estimate an optimal velocity, 2mm/sec, for maximizing the number of cells binding and the critical binding force. At higher velocities, shear forces (> 0.48 dyne) will break existing bonds and prevent the formation of new ones. This detection micro-device can be assembled with other lab-on-a-chip components for follow-up gene and protein analysis.

Synthesis and evaluation of a glutamic acid-modified hPAMAM complex as a promising versatile gene carrier.

Science.gov (United States)

Hemmati, Mohammad; Kazemi, Bahram; Najafi, Farhood; Zarebkohan, Amir; Shirkoohi, Reza

2016-01-01

Hyperbranched poly(amidoamine) (HPAMAM), structurally analogous to polyamidoamine dendrimer (PAMAM) dendrimers, has been suggested to be an effective carrier for gene delivery. In the present study, glutamic acid-modified hPAMAM was developed as a novel non-viral gene carrier for the first time. The hPAMAM was synthesized by using a modified one-pot method. DNA was found to be bound to hPAMAM at different weight ratios (WhPAMAM/WDNA). The resulting HPAMAM-Glu20 was able to efficiently protect the encapsulated-DNA against degradation for over 2 h. In addition to low cytotoxicity, the transfection efficiency of hPAMAM-Glu20 represented much higher (p glutamic amino acid (Glu)-based gene delivery is an economical, effective and biocompatible method.

Knock-down of transcript abundance of a family of Kunitz proteinase inhibitor genes in white clover (Trifolium repens) reveals a redundancy and diversity of gene function.

Science.gov (United States)

Islam, Afsana; Leung, Susanna; Burgess, Elisabeth P J; Laing, William A; Richardson, Kim A; Hofmann, Rainer W; Dijkwel, Paul P; McManus, Michael T

2015-12-01

The transcriptional regulation of four phylogenetically distinct members of a family of Kunitz proteinase inhibitor (KPI) genes isolated from white clover (Trifolium repens; designated Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5) has been investigated to determine their wider functional role. The four genes displayed differential transcription during seed germination, and in different tissues of the mature plant, and transcription was also ontogenetically regulated. Heterologous over-expression of Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5 in Nicotiana tabacum retarded larval growth of the herbivore Spodoptera litura, and an increase in the transcription of the pathogenesis-related genes PR1 and PR4 was observed in the Tr-KPI1 and Tr-KPI4 over-expressing lines. RNA interference (RNAi) knock-down lines in white clover displayed significantly altered vegetative growth phenotypes with inhibition of shoot growth and a stimulation of root growth, while knock-down of Tr-KPI1, Tr-KPI2 and Tr-KPI5 transcript abundance also retarded larval growth of S. litura. Examination of these RNAi lines revealed constitutive stress-associated phenotypes as well as altered transcription of cellular signalling genes. These results reveal a functional redundancy across members of the KPI gene family. Further, the regulation of transcription of at least one member of the family, Tr-KPI2, may occupy a central role in the maintenance of a cellular homeostasis. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

An RNA-seq transcriptome analysis of histone modifiers and RNA silencing genes in soybean during floral initiation process.

Directory of Open Access Journals (Sweden)

Lim Chee Liew

Full Text Available Epigenetics has been recognised to play vital roles in many plant developmental processes, including floral initiation through the epigenetic regulation of gene expression. The histone modifying proteins that mediate these modifications involve the SET domain-containing histone methyltransferases, JmjC domain-containing demethylase, acetylases and deacetylases. In addition, RNA interference (RNAi-associated genes are also involved in epigenetic regulation via RNA-directed DNA methylation and post-transcriptional gene silencing. Soybean, a major crop legume, requires a short day to induce flowering. How histone modifications regulate the plant response to external cues that initiate flowering is still largely unknown. Here, we used RNA-seq to address the dynamics of transcripts that are potentially involved in the epigenetic programming and RNAi mediated gene silencing during the floral initiation of soybean. Soybean is a paleopolyploid that has been subjected to at least two rounds of whole genome duplication events. We report that the expanded genomic repertoire of histone modifiers and RNA silencing genes in soybean includes 14 histone acetyltransferases, 24 histone deacetylases, 47 histone methyltransferases, 15 protein arginine methyltransferases, 24 JmjC domain-containing demethylases and 47 RNAi-associated genes. To investigate the role of these histone modifiers and RNA silencing genes during floral initiation, we compared the transcriptional dynamics of the leaf and shoot apical meristem at different time points after a short-day treatment. Our data reveal that the extensive activation of genes that are usually involved in the epigenetic programming and RNAi gene silencing in the soybean shoot apical meristem are reprogrammed for floral development following an exposure to inductive conditions.

Peripheral blood transcriptome sequencing reveals rejection-relevant genes in long-term heart transplantation.

Science.gov (United States)

Chen, Yan; Zhang, Haibo; Xiao, Xue; Jia, Yixin; Wu, Weili; Liu, Licheng; Jiang, Jun; Zhu, Baoli; Meng, Xu; Chen, Weijun

2013-10-03

Peripheral blood-based gene expression patterns have been investigated as biomarkers to monitor the immune system and rule out rejection after heart transplantation. Recent advances in the high-throughput deep sequencing (HTS) technologies provide new leads in transcriptome analysis. By performing Solexa/Illumina's digital gene expression (DGE) profiling, we analyzed gene expression profiles of PBMCs from 6 quiescent (grade 0) and 6 rejection (grade 2R&3R) heart transplant recipients at more than 6 months after transplantation. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out in an independent validation cohort of 47 individuals from three rejection groups (ISHLT, grade 0,1R, 2R&3R). Through DGE sequencing and qPCR validation, 10 genes were identified as informative genes for detection of cardiac transplant rejection. A further clustering analysis showed that the 10 genes were not only effective for distinguishing patients with acute cardiac allograft rejection, but also informative for discriminating patients with renal allograft rejection based on both blood and biopsy samples. Moreover, PPI network analysis revealed that the 10 genes were connected to each other within a short interaction distance. We proposed a 10-gene signature for heart transplant patients at high-risk of developing severe rejection, which was found to be effective as well in other organ transplant. Moreover, we supposed that these genes function systematically as biomarkers in long-time allograft rejection. Further validation in broad transplant population would be required before the non-invasive biomarkers can be generally utilized to predict the risk of transplant rejection. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Accumulation of Phenolic Compounds and Expression Profiles of Phenolic Acid Biosynthesis-Related Genes in Developing Grains of White, Purple, and Red Wheat.

Science.gov (United States)

Ma, Dongyun; Li, Yaoguang; Zhang, Jian; Wang, Chenyang; Qin, Haixia; Ding, Huina; Xie, Yingxin; Guo, Tiancai

2016-01-01

Polyphenols in whole grain wheat have potential health benefits, but little is known about the expression patterns of phenolic acid biosynthesis genes and the accumulation of phenolic acid compounds in different-colored wheat grains. We found that purple wheat varieties had the highest total phenolic content (TPC) and antioxidant activity. Among phenolic acid compounds, bound ferulic acid, vanillic, and caffeic acid levels were significantly higher in purple wheat than in white and red wheat, while total soluble phenolic acid, soluble ferulic acid, and vanillic acid levels were significantly higher in purple and red wheat than in white wheat. Ferulic acid and syringic acid levels peaked at 14 days after anthesis (DAA), whereas p-coumaric acid and caffeic acid levels peaked at 7 DAA, and vanillic acid levels gradually increased during grain filling and peaked near ripeness (35 DAA). Nine phenolic acid biosynthesis pathway genes (TaPAL1, TaPAL2, TaC3H1, TaC3H2, TaC4H, Ta4CL1, Ta4CL2, TaCOMT1, and TaCOMT2) exhibited three distinct expression patterns during grain filling, which may be related to the different phenolic acids levels. White wheat had higher phenolic acid contents and relatively high gene expression at the early stage, while purple wheat had the highest phenolic acid contents and gene expression levels at later stages. These results suggest that the expression of phenolic acid biosynthesis genes may be closely related to phenolic acids accumulation.

Evidence of major genes for exercise heart rate and blood pressure at baseline and in response to 20 weeks of endurance training: the HERITAGE family study.

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An, P; Borecki, I B; Rankinen, T; Pérusse, L; Leon, A S; Skinner, J S; Wilmore, J H; Bouchard, C; Rao, D C

2003-10-01

Major gene effects on exercise heart rate (HR) and blood pressure (BP) measured at 50 W and 80 % maximal oxygen uptake (VO (2)max) were assessed in 99 White families in the HERITAGE Family Study. Exercise HR and BP were measured both before and after 20 weeks of endurance training. The baseline phenotypes were adjusted for the effects of age and BMI, whereas the training responses (post-training minus baseline) were adjusted for the effects of age, BMI and the corresponding baseline values, within four sex-by-generation groups. Baseline exercise HR at 50 W was under the influence of a major recessive gene and a multifactorial component, which accounted for 30 % and 27 % of the variance, respectively. The training response was found to be under the influence of a major dominant gene, which accounted for 27 % of the variance. These significant major gene effects were independent of the effects of cigarette smoking, baseline VO (2)max, and the resting HR levels. No significant interactions were found between genotype and age, sex, or BMI. No major gene effect was found for exercise BP. Instead, we found the baseline exercise BP at 50 W and 80 % VO (2)max and the training response at 50 W were solely influenced by multifactorial effects, which accounted for about 50 %, 40 % and 20 % of the variance, respectively. No familial resemblance was found for training responses in exercise HR or BP at 80 % VO (2)max. Segregation analysis also was carried out for exercise HR in Whites pooled with a small sample of Blacks in HERITAGE. Similar major effects were found, but the transmission from parents to offspring did not follow Mendelian expectations, suggesting sample heterogeneity. In conclusion, submaximal exercise HR at baseline and in response to endurance training was influenced by putative major genes, with no evidence of interactions with sex, age or BMI, in contrast to a multifactorial etiology for exercise BP.

Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients.

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Felts, Sara J; Van Keulen, Virginia P; Scheid, Adam D; Allen, Kathleen S; Bradshaw, Renee K; Jen, Jin; Peikert, Tobias; Middha, Sumit; Zhang, Yuji; Block, Matthew S; Markovic, Svetomir N; Pease, Larry R

2015-11-01

Melanoma patients exhibit changes in immune responsiveness in the local tumor environment, draining lymph nodes, and peripheral blood. Immune-targeting therapies are revolutionizing melanoma patient care increasingly, and studies show that patients derive clinical benefit from these newer agents. Nonetheless, predicting which patients will benefit from these costly therapies remains a challenge. In an effort to capture individual differences in immune responsiveness, we are analyzing patterns of gene expression in human peripheral blood cells using RNAseq. Focusing on CD4+ peripheral blood cells, we describe multiple categories of immune regulating genes, which are expressed in highly ordered patterns shared by cohorts of healthy subjects and stage IV melanoma patients. Despite displaying conservation in overall transcriptome structure, CD4+ peripheral blood cells from melanoma patients differ quantitatively from healthy subjects in the expression of more than 2000 genes. Moreover, 1300 differentially expressed genes are found in transcript response patterns following activation of CD4+ cells ex vivo, suggesting that widespread functional discrepancies differentiate the immune systems of healthy subjects and melanoma patients. While our analysis reveals that the transcriptome architecture characteristic of healthy subjects is maintained in cancer patients, the genes expressed differentially among individuals and across cohorts provide opportunities for understanding variable immune states as well as response potentials, thus establishing a foundation for predicting individual responses to stimuli such as immunotherapeutic agents.

The Trojan Horse Liposome Technology for Nonviral Gene Transfer across the Blood-Brain Barrier

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Ruben J. Boado

2011-01-01

Full Text Available The application of blood-borne gene therapy protocols to the brain is limited by the presence of the blood-brain barrier (BBB. Viruses have been extensively used as gene delivery systems. However, their efficacy in brain is limited by the lack of transport across the BBB following intravenous (IV administration. Recent progress in the “Trojan Horse Liposome” (THL technology applied to transvascular non-viral gene therapy of the brain presents a promising solution to the trans-vascular brain gene delivery problem. THLs are comprised of immunoliposomes carrying nonviral gene expression plasmids. The tissue target specificity of the THL is provided by peptidomimetic monoclonal antibody (MAb component of the THL, which binds to specific endogenous receptors located on both the BBB and on brain cellular membranes, for example, insulin receptor and transferrin receptor. These MAbs mediate (a receptor-mediated transcytosis of the THL complex through the BBB, (b endocytosis into brain cells and (c transport to the brain cell nuclear compartment. The expression of the transgene in brain may be restricted using tissue/cell specific gene promoters. This manuscript presents an overview on the THL transport technology applied to brain disorders, including lysosomal storage disorders and Parkinson's disease.

Gene expression changes in blood RNA after swimming in a chlorinated pool.

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Salas, Lucas A; Font-Ribera, Laia; Bustamante, Mariona; Sumoy, Lauro; Grimalt, Joan O; Bonnin, Sarah; Aguilar, Maria; Mattlin, Heidi; Hummel, Manuela; Ferrer, Anna; Kogevinas, Manolis; Villanueva, Cristina M

2017-08-01

Exposure to disinfection by-products (DBP) such as trihalomethanes (THM) in swimming pools has been linked to adverse health effects in humans, but their biological mechanisms are unclear. We evaluated short-term changes in blood gene expression of adult recreational swimmers after swimming in a chlorinated pool. Volunteers swam 40min in an indoor chlorinated pool. Blood samples were drawn and four THM (chloroform, bromodichloromethane, dibromochloromethane and bromoform) were measured in exhaled breath before and after swimming. Intensity of physical activity was measured as metabolic equivalents (METs). Gene expression in whole blood mRNA was evaluated using IlluminaHumanHT-12v3 Expression-BeadChip. Linear mixed models were used to evaluate the relationship between gene expression changes and THM exposure. Thirty-seven before-after pairs were analyzed. The median increase from baseline to after swimming were: 0.7 to 2.3 for MET, and 1.4 to 7.1μg/m 3 for exhaled total THM (sum of the four THM). Exhaled THM increased on average 0.94μg/m 3 per 1 MET. While 1643 probes were differentially expressed post-exposure. Of them, 189 were also associated with exhaled levels of individual/total THM or MET after False Discovery Rate. The observed associations with the exhaled THM were low to moderate (Log-fold change range: -0.17 to 0.15). In conclusion, we identified short-term gene expression changes associated with swimming in a pool that were minor in magnitude and their biological meaning was unspecific. The high collinearity between exhaled THM levels and intensity of physical activity precluded mutually adjusted models with both covariates. These exploratory results should be validated in future studies. Copyright © 2017. Published by Elsevier B.V.

Two White Spot Syndrome Virus MicroRNAs Target the Dorsal Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp.

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Ren, Qian; Huang, Xin; Cui, Yalei; Sun, Jiejie; Wang, Wen; Zhang, Xiaobo

2017-04-15

In eukaryotes, microRNAs (miRNAs) serve as regulators of many biological processes, including virus infection. An miRNA can generally target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs has not yet been extensively explored during virus infection. This study found that the Spaztle (Spz)-Toll-Dorsal-antilipopolysaccharide factor (ALF) signaling pathway plays a very important role in antiviral immunity against invasion of white spot syndrome virus (WSSV) in shrimp ( Marsupenaeus japonicus ). Dorsal , the central gene in the Toll pathway, was targeted by two viral miRNAs (WSSV-miR-N13 and WSSV-miR-N23) during WSSV infection. The regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo , leading to virus infection. Our study contributes novel insights into the viral miRNA-mediated Toll signaling pathway during the virus-host interaction. IMPORTANCE An miRNA can target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs during virus infection has not yet been extensively explored. The results of this study indicated that the shrimp Dorsal gene, the central gene in the Toll pathway, was targeted by two viral miRNAs during infection with white spot syndrome virus. Regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo , leading to virus infection. Our study provides new insight into the viral miRNA-mediated Toll signaling pathway in virus-host interactions. Copyright © 2017 American Society for Microbiology.

Identification of a set of endogenous reference genes for miRNA expression studies in Parkinson's disease blood samples.

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Serafin, Alice; Foco, Luisa; Blankenburg, Hagen; Picard, Anne; Zanigni, Stefano; Zanon, Alessandra; Pramstaller, Peter P; Hicks, Andrew A; Schwienbacher, Christine

2014-10-10

Research on microRNAs (miRNAs) is becoming an increasingly attractive field, as these small RNA molecules are involved in several physiological functions and diseases. To date, only few studies have assessed the expression of blood miRNAs related to Parkinson's disease (PD) using microarray and quantitative real-time PCR (qRT-PCR). Measuring miRNA expression involves normalization of qRT-PCR data using endogenous reference genes for calibration, but their choice remains a delicate problem with serious impact on the resulting expression levels. The aim of the present study was to evaluate the suitability of a set of commonly used small RNAs as normalizers and to identify which of these miRNAs might be considered reliable reference genes in qRT-PCR expression analyses on PD blood samples. Commonly used reference genes snoRNA RNU24, snRNA RNU6B, snoRNA Z30 and miR-103a-3p were selected from the literature. We then analyzed the effect of using these genes as reference, alone or in any possible combination, on the measured expression levels of the target genes miR-30b-5p and miR-29a-3p, which have been previously reported to be deregulated in PD blood samples. We identified RNU24 and Z30 as a reliable and stable pair of reference genes in PD blood samples.

The anticoagulant ability of ferulic acid and its applications for improving the blood compatibility of silk fibroin

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Wang Song; Gao Zhen; Chen Xiaomeng; Lian Xiaojie; Zhu Hesun [School of Material Science and Engineering, Beijing Institute of Technology, Beijing 100081 (China); Zheng Jun; Sun Lizhong [Department of Cardiac Surgery, Cardiovascular Institute and Fu Wai Hospital, CAMS and PUMC, Beijing 100037 (China)], E-mail: wangsongbit@hotmail.com

2008-12-15

The hemocompatibility of silk fibroin (SF) was improved with ferulic acid (FA) by graft polymerization. Ferulic acid is an active ingredient of many Chinese herbal medicines, such as Chuanxiong (Rhizoma ligustici wallichii), Danggui (Angelica sinensis) and Awei (Asafoetida giantfennel), which have been used to treat cardiovascular diseases by Chinese physicians for thousands of years. The inhibitory functions of FA on blood coagulation and erythrocyte agglutination were first characterized by a Lee-White test tube method and a micropipette technique, respectively. Then, FA was immobilized on SF by graft polymerization and the surface composition of modified SF was characterized by attenuated total reflectance Fourier-transform infrared (ATR-FTIR), x-ray photoelectron spectroscopy (XPS) and optical microscopy. The anticoagulant activity of modified SF was assessed, respectively, by in vitro clotting time measurements on a photo-optical clot detection instrument and with the Lee-White test tube method. The test results indicated that in comparison to untreated SF, the anticoagulant activity of modified SF has been improved significantly. Moreover, the SF surface composition is altered by FA but its {beta}-sheet conformation is not disturbed.

Dialysate White Blood Cell Change after Initial Antibiotic Treatment Represented the Patterns of Response in Peritoneal Dialysis-Related Peritonitis.

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Tantiyavarong, Pichaya; Traitanon, Opas; Chuengsaman, Piyatida; Patumanond, Jayanton; Tasanarong, Adis

2016-01-01

Background. Patients with peritoneal dialysis-related peritonitis usually have different responses to initial antibiotic treatment. This study aimed to explore the patterns of response by using the changes of dialysate white blood cell count on the first five days of the initial antibiotic treatment. Materials and Methods. A retrospective cohort study was conducted. All peritoneal dialysis-related peritonitis episodes from January 2014 to December 2015 were reviewed. We categorized the patterns of antibiotic response into 3 groups: early response, delayed response, and failure group. The changes of dialysate white blood cell count for each pattern were determined by multilevel regression analysis. Results. There were 644 episodes in 455 patients: 378 (58.7%) of early response, 122 (18.9%) of delayed response, and 144 (22.3%) of failure episodes. The patterns of early, delayed, and failure groups were represented by the average rate reduction per day of dialysate WBC of 68.4%, 34.0%, and 14.2%, respectively (p value patterns, which were categorized by types of responses, have variable rates of WBC declining. Clinicians should focus on the delayed response and failure patterns in order to make a decision whether to continue medical therapies or to aggressively remove the peritoneal catheter.

Accuracy of home versus ambulatory blood pressure monitoring in the diagnosis of white-coat and masked hypertension.

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Kang, Yuan-Yuan; Li, Yan; Huang, Qi-Fang; Song, Jie; Shan, Xiao-Li; Dou, Yu; Xu, Xin-Juan; Chen, Shou-Hong; Wang, Ji-Guang

2015-08-01

We investigated accuracy of home blood pressure (BP) monitoring in the diagnosis of white-coat and masked hypertension in comparison with ambulatory BP monitoring. Our study participants were enrolled in the China Ambulatory and Home BP Registry, and underwent clinic, home, and 24-h ambulatory BP measurements. We defined white-coat hypertension as an elevated clinic SBP/DBP (≥140/90 mmHg) and a normal 24-h ambulatory (coat hypertension (13.1 vs. 19.9%), masked hypertension (17.8 vs. 13.1%), and sustained hypertension (46.4 vs. 39.6%) significantly (P ≤ 0.02) differed between 24-h ambulatory and home BP monitoring. In treated patients (n = 1201), only the prevalence of masked hypertension differed significantly (18.7 vs. 14.5%; P = 0.005). Regardless of the treatment status, home compared with 24-h ambulatory BP had low sensitivity (range 47-74%), but high specificity (86-94%), and accordingly low positive (41-87%), but high negative predictive values (80-94%), and had moderate diagnostic agreement (82-85%) and Kappa statistic (0.41-0.66). In untreated and treated patients, age advancing was associated with a higher prevalence of white-coat hypertension and a lower prevalence of masked hypertension defined by 24-h ambulatory (P ≤ 0.03) but not home BP (P ≥ 0.10). Home BP monitoring has high specificity, but low sensitivity in the diagnosis of white-coat and masked hypertension, and may therefore behave as a complementary to, but not a replacement of, ambulatory BP monitoring.

The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration

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C. Biz

2009-12-01

Full Text Available Metabolic syndrome is associated with an increased risk of developing cardiovascular diseases and Plasminogen activator inhibitor 1 (PAI-1 overexpression may play a significant role in this process. A positive correlation between adipose tissue gene expression of PAI-1 and its serum concentration has been reported. Furthermore, high serum levels of thyroid hormones (T3 and T4 and PAI-1 have been observed in obese children. The present study evaluates the impact of thyroid hormone treatment on white adipose tissue PAI-1 gene expression and its serum concentration. Male Wistar rats (60 days old were treated for three weeks with T4 (50 µg/day, Hyper or with saline (control. Additionally, 3T3-L1 adipocytes were treated for 24 h with T4 (100 nM or T3 (100 nM. PAI-1 gene expression was determined by real-time PCR, while the serum concentration of PAI-1 was measured by ELISA using a commercial kit (Innovative Research, USA. Both the serum concentration of PAI-1 and mRNA levels were similar between groups in retroperitoneal and epididymal white adipose tissue. Using 3T3-L1 adipocytes, in vitro treatment with T4 and T3 increased the gene expression of PAI-1, suggesting non-genomic and genomic effects, respectively. These results demonstrate that thyroid hormones have different effects in vitro and in vivo on PAI-1 gene expression in adipocytes.

Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

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DeYoung Joseph

2009-08-01

Full Text Available Abstract Background Amyotrophic Lateral Sclerosis (ALS is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in gene expression profiles in whole blood of ALS patients. Results Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4% showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA was used to find disease-related networks (modules and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls and third dataset (63 patients and 63 controls, thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS. Conclusion This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.

Gene expression markers of age-related inflammation in two human cohorts.

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Pilling, Luke C; Joehanes, Roby; Melzer, David; Harries, Lorna W; Henley, William; Dupuis, Josée; Lin, Honghuang; Mitchell, Marcus; Hernandez, Dena; Ying, Sai-Xia; Lunetta, Kathryn L; Benjamin, Emelia J; Singleton, Andrew; Levy, Daniel; Munson, Peter; Murabito, Joanne M; Ferrucci, Luigi

2015-10-01

Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (>800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n=2422, ages 40-92 yrs) and InCHIANTI study (n=694, ages 30-104 yrs), with Affymetrix and Illumina expression arrays respectively (>17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing. In FHS, IL6 expression was not associated with IL6 protein levels in blood. 102 genes (0.6% of 17,324 expressed) statistically mediated the age-IL6 association of which 25 replicated in InCHIANTI (including 5 of the 10 largest effect genes). The largest effect gene (SLC4A10, coding for NCBE, a sodium bicarbonate transporter) mediated 19% (adjusted CI 8.9 to 34.1%) and replicated by PCR in InCHIANTI (n=194, 35.6% mediated, p=0.01). Other replicated mediators included PRF1 (perforin, a cytolytic protein in cytotoxic T lymphocytes and NK cells) and IL1B (Interleukin 1 beta): few other cytokines were significant mediators. This transcriptome-wide study on human blood identified a small distinct set of genes that statistically mediate the age-IL6 association. Findings are robust across two cohorts and different expression technologies. Raised IL6 levels may not derive from circulating white cells in age related inflammation. Published by Elsevier Inc.

Gene Expression in Uterine Leiomyoma from Tumors Likely to Be Growing (from Black Women over 35) and Tumors Likely to Be Non-Growing (from White Women over 35)

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Davis, Barbara J.; Risinger, John I.; Chandramouli, Gadisetti V. R.; Bushel, Pierre R.; Baird, Donna Day; Peddada, Shyamal D.

2013-01-01

The study of uterine leiomyomata (fibroids) provides a unique opportunity to investigate the physiological and molecular determinants of hormone dependent tumor growth and spontaneous tumor regression. We conducted a longitudinal clinical study of premenopausal women with leiomyoma that showed significantly different growth rates between white and black women depending on their age. Growth rates for leiomyoma were on average much higher from older black women than for older white women, and we now report gene expression pattern differences in tumors from these two groups of study participants. Total RNA from 52 leiomyoma and 8 myometrial samples were analyzed using Affymetrix Gene Chip expression arrays. Gene expression data was first compared between all leiomyoma and normal myometrium and then between leiomyoma from older black women (age 35 or older) and from older white women. Genes that were found significant in pairwise comparisons were further analyzed for canonical pathways, networks and biological functions using the Ingenuity Pathway Analysis (IPA) software. Whereas our comparison of leiomyoma to myometrium produced a very large list of genes highly similar to numerous previous studies, distinct sets of genes and signaling pathways were identified in comparisons of older black and white women whose tumors were likely to be growing and non-growing, respectively. Key among these were genes associated with regulation of apoptosis. To our knowledge, this is the first study to compare two groups of tumors that are likely to have different growth rates in order to reveal molecular signals likely to be influential in tumor growth. PMID:23785396

Transcriptome analysis describing new immunity and defense genes in peripheral blood mononuclear cells of rheumatoid arthritis patients.

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Vitor Hugo Teixeira

Full Text Available BACKGROUND: Large-scale gene expression profiling of peripheral blood mononuclear cells from Rheumatoid Arthritis (RA patients could provide a molecular description that reflects the contribution of diverse cellular responses associated with this disease. The aim of our study was to identify peripheral blood gene expression profiles for RA patients, using Illumina technology, to gain insights into RA molecular mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: The Illumina Human-6v2 Expression BeadChips were used for a complete genome-wide transcript profiling of peripheral blood mononuclear cells (PBMCs from 18 RA patients and 15 controls. Differential analysis per gene was performed with one-way analysis of variance (ANOVA and P values were adjusted to control the False Discovery Rate (FDR<5%. Genes differentially expressed at significant level between patients and controls were analyzed using Gene Ontology (GO in the PANTHER database to identify biological processes. A differentially expression of 339 Reference Sequence genes (238 down-regulated and 101 up-regulated between the two groups was observed. We identified a remarkably elevated expression of a spectrum of genes involved in Immunity and Defense in PBMCs of RA patients compared to controls. This result is confirmed by GO analysis, suggesting that these genes could be activated systemically in RA. No significant down-regulated ontology groups were found. Microarray data were validated by real time PCR in a set of nine genes showing a high degree of correlation. CONCLUSIONS/SIGNIFICANCE: Our study highlighted several new genes that could contribute in the identification of innovative clinical biomarkers for diagnostic procedures and therapeutic interventions.

Prognostic importance of white coat and masked hypertention

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Gustavsen, Pia; Hansen, Tine

2009-01-01

The growing use of ambulatory blood pressure monitoring has led to an increased awareness of the two types of discrepancy between office blood pressure and ambulatory blood pressure, called white coat hypertension (WCH) and masked hypertension (MH). Based on several longitudinal studies, WCH...

Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression.

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Hollander, Zsuzsanna; Chen, Virginia; Sidhu, Keerat; Lin, David; Ng, Raymond T; Balshaw, Robert; Cohen-Freue, Gabriela V; Ignaszewski, Andrew; Imai, Carol; Kaan, Annemarie; Tebbutt, Scott J; Wilson-McManus, Janet E; McMaster, Robert W; Keown, Paul A; McManus, Bruce M

2013-02-01

Acute rejection in cardiac transplant patients remains a contributory factor to limited survival of implanted hearts. Currently, there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplant acute cellular rejection. Such a development would be of great value in personalizing immunosuppressive treatment. Recipient age, donor age, cold ischemic time, warm ischemic time, panel-reactive antibody, gender mismatch, blood type mismatch and human leukocyte antigens (HLA-A, -B and -DR) mismatch between recipients and donors were tested in 53 heart transplant patients for their power to predict post-transplant acute cellular rejection. Donor transplant biopsy and recipient pre-transplant blood were also examined for the presence of genomic biomarkers in 7 rejection and 11 non-rejection patients, using non-targeted data mining techniques. The biomarker based on the 8 clinical variables had an area under the receiver operating characteristic curve (AUC) of 0.53. The pre-transplant recipient blood gene-based panel did not yield better performance, but the donor heart tissue gene-based panel had an AUC = 0.78. A combination of 25 probe sets from the transplant donor biopsy and 18 probe sets from the pre-transplant recipient whole blood had an AUC = 0.90. Biologic pathways implicated include VEGF- and EGFR-signaling, and MAPK. Based on this study, the best predictive biomarker panel contains genes from recipient whole blood and donor myocardial tissue. This panel provides clinically relevant prediction power and, if validated, may personalize immunosuppressive treatment and rejection monitoring. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Is erythropoietin gene a modifier factor in amyotrophic lateral sclerosis?

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Ghezzi, Serena; Del Bo, Roberto; Scarlato, Marina; Nardini, Martina; Carlesi, Cecilia; Prelle, Alessandro; Corti, Stefania; Mancuso, Michelangelo; Briani, Chiara; Siciliano, Gabriele; Murri, Luigi; Bresolin, Nereo; Comi, Giacomo Pietro

2009-05-01

To investigate the role of erythropoietin (EPO) as genetic determinant in the susceptibility to sporadic amyotrophic lateral sclerosis (SALS). We sequenced a 259-bp region spanning the 3'hypoxia-responsive element of the EPO gene in 222 Italian SALS patients and 204 healthy subjects, matched for age and ethnic origin. No potentially causative variation was detected in SALS subjects; in addition, two polymorphic variants (namely C3434T and G3544T) showed the same genotype and haplotype frequencies in patients and controls. Conversely, a weak but significant association between G3544T and age of disease onset was observed (p=0.04). Overall, our data argue against the hypothesis of EPO as a genetic risk factor for motor neuron dysfunction, at least in Italian population. However, further studies on larger cohort of patients are needed to confirm the evidence of EPO gene as modifier factor.

Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT polymorphism in a prospective cohort study among women in China.

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Qing Lan

Full Text Available A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR, 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003. Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030. Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations.

Differential gene expression profiles of peripheral blood mononuclear cells in childhood asthma.

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Kong, Qian; Li, Wen-Jing; Huang, Hua-Rong; Zhong, Ying-Qiang; Fang, Jian-Pei

2015-05-01

Asthma is a common childhood disease with strong genetic components. This study compared whole-genome expression differences between asthmatic young children and healthy controls to identify gene signatures of childhood asthma. Total RNA extracted from peripheral blood mononuclear cells (PBMC) was subjected to microarray analysis. QRT-PCR was performed to verify the microarray results. Classification and functional characterization of differential genes were illustrated by hierarchical clustering and gene ontology analysis. Multiple logistic regression (MLR) analysis, receiver operating characteristic (ROC) curve analysis, and discriminate power were used to scan asthma-specific diagnostic markers. For fold-change>2 and p childhood asthma model for prediction and diagnosis.

Remarkable stability in patterns of blood-stage gene expression during episodes of non-lethal Plasmodium yoelii malaria.

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Cernetich-Ott, Amy; Daly, Thomas M; Vaidya, Akhil B; Bergman, Lawrence W; Burns, James M

2012-08-06

Microarray studies using in vitro cultures of synchronized, blood-stage Plasmodium falciparum malaria parasites have revealed a 'just-in-time' cascade of gene expression with some indication that these transcriptional patterns remain stable even in the presence of external stressors. However, direct analysis of transcription in P. falciparum blood-stage parasites obtained from the blood of infected patients suggests that parasite gene expression may be modulated by factors present in the in vivo environment of the host. The aim of this study was to examine changes in gene expression of the rodent malaria parasite, Plasmodium yoelii 17X, while varying the in vivo setting of replication. Using P. yoelii 17X parasites replicating in vivo, differential gene expression in parasites isolated from individual mice, from independent infections, during ascending, peak and descending parasitaemia and in the presence and absence of host antibody responses was examined using P. yoelii DNA microarrays. A genome-wide analysis to identify coordinated changes in groups of genes associated with specific biological pathways was a primary focus, although an analysis of the expression patterns of two multi-gene families in P. yoelii, the yir and pyst-a families, was also completed. Across experimental conditions, transcription was surprisingly stable with little evidence for distinct transcriptional states or for consistent changes in specific pathways. Differential gene expression was greatest when comparing differences due to parasite load and/or host cell availability. However, the number of differentially expressed genes was generally low. Of genes that were differentially expressed, many involved biologically diverse pathways. There was little to no differential expression of members of the yir and pyst-a multigene families that encode polymorphic proteins associated with the membrane of infected erythrocytes. However, a relatively large number of these genes were expressed during

Plasma and White Blood Cells Show Different miRNA Expression Profiles in Parkinson's Disease.

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Schwienbacher, Christine; Foco, Luisa; Picard, Anne; Corradi, Eloina; Serafin, Alice; Panzer, Jörg; Zanigni, Stefano; Blankenburg, Hagen; Facheris, Maurizio F; Giannini, Giulia; Falla, Marika; Cortelli, Pietro; Pramstaller, Peter P; Hicks, Andrew A

2017-06-01

Parkinson's disease (PD) diagnosis is based on the assessment of motor symptoms, which manifest when more than 50% of dopaminergic neurons are degenerated. To date, no validated biomarkers are available for the diagnosis of PD. The aims of the present study are to evaluate whether plasma and white blood cells (WBCs) are interchangeable biomarker sources and to identify circulating plasma-based microRNA (miRNA) biomarkers for an early detection of PD. We profiled plasma miRNA levels in 99 L-dopa-treated PD patients from two independent data collections, in ten drug-naïve PD patients, and in unaffected controls matched by sex and age. We evaluated expression levels by reverse transcription and quantitative real-time PCR (RT-qPCR) and combined the results from treated PD patients using a fixed effect inverse-variance weighted meta-analysis. We revealed different expression profiles comparing plasma and WBCs and drug-naïve and L-dopa-treated PD patients. We observed an upregulation trend for miR-30a-5p in L-dopa-treated PD patients and investigated candidate target genes by integrated in silico analyses. We could not analyse miR-29b-3p, normally expressed in WBCs, due to the very low expression in plasma. We observed different expression profiles in WBCs and plasma, suggesting that they are both suitable but not interchangeable peripheral sources for biomarkers. We revealed miR-30a-5p as a potential biomarker for PD in plasma. In silico analyses suggest that miR-30a-5p might have a regulatory role in mitochondrial dynamics and autophagy. Further investigations are needed to confirm miR-30a-5p deregulation and targets and to investigate the influence of L-dopa treatment on miRNA expression levels.

Age gene expression and coexpression progressive signatures in peripheral blood leukocytes.

Science.gov (United States)

Irizar, Haritz; Goñi, Joaquín; Alzualde, Ainhoa; Castillo-Triviño, Tamara; Olascoaga, Javier; Lopez de Munain, Adolfo; Otaegui, David

2015-12-01

Both cellular senescence and organismic aging are known to be dynamic processes that start early in life and progress constantly during the whole life of the individual. In this work, with the objective of identifying signatures of age-related progressive change at the transcriptomic level, we have performed a whole-genome gene expression analysis of peripheral blood leukocytes in a group of healthy individuals with ages ranging from 14 to 93 years. A set of genes with progressively changing gene expression (either increase or decrease with age) has been identified and contextualized in a coexpression network. A modularity analysis has been performed on this network and biological-term and pathway enrichment analyses have been used for biological interpretation of each module. In summary, the results of the present work reveal the existence of a transcriptomic component that shows progressive expression changes associated to age in peripheral blood leukocytes, highlighting both the dynamic nature of the process and the need to complement young vs. elder studies with longitudinal studies that include middle aged individuals. From the transcriptional point of view, immunosenescence seems to be occurring from a relatively early age, at least from the late 20s/early 30s, and the 49-56 year old age-range appears to be critical. In general, the genes that, according to our results, show progressive expression changes with aging are involved in pathogenic/cellular processes that have classically been linked to aging in humans: cancer, immune processes and cellular growth vs. maintenance. Copyright © 2015 Elsevier Inc. All rights reserved.

Anchoring of self-assembled plasmid DNA/ anti-DNA antibody/cationic lipid micelles on bisphosphonate-modified stent for cardiovascular gene delivery

Directory of Open Access Journals (Sweden)

Ma G

2013-03-01

Full Text Available Guilei Ma,1,# Yong Wang,1,# Ilia Fishbein,2 Mei Yu,1 Linhua Zhang,1 Ivan S Alferiev,2 Jing Yang,1 Cunxian Song,1 Robert J Levy2 1Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People's Republic of China; 2Children's Hospital of Philadelphia, Abramson Research Building, Philadelphia, PA, USA #These authors contributed equally to this work Purpose: To investigate the anchoring of plasmid DNA/anti-DNA antibody/cationic lipid tri-complex (DAC micelles onto bisphosphonate-modified 316 L coronary stents for cardiovascular site-specific gene delivery. Methods: Stents were first modified with polyallylamine bisphosphonate (PAA-BP, thereby enabling the retention of a PAA-BP molecular monolayer that permits the anchoring (via vector-binding molecules of DAC micelles. DAC micelles were then chemically linked onto the PAA-BP-modified stents by using N-succinimidyl-3-(2-pyridyldithiol-propionate (SPDP as a crosslinker. Rhodamine-labeled DNA was used to assess the anchoring of DAC micelles, and radioactive-labeled antibody was used to evaluate binding capacity and stability. DAC micelles (encoding green fluorescent protein were tethered onto the PAA-BP-modified stents, which were assessed in cell culture. The presence of a PAA-BP molecular monolayer on the steel surface was confirmed by X-ray photoelectron spectroscopy and atomic force microscope analysis. Results: The anchoring of DAC micelles was generally uniform and devoid of large-scale patches of defects. Isotopic quantification confirmed that the amount of antibody chemically linked on the stents was 17-fold higher than that of the physical adsorbed control stents and its retention time was also significantly longer. In cell culture, numerous green fluorescent protein-positive cells were found on the PAA-BP modified stents, which demonstrated high localization and efficiency of gene delivery. Conclusion: The DAC micelle

Vitamin D3 deficiency increases DNA damage and modify the expression of genes associated with hypertension in normotensive and hypertensive rats

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Carla Silva Machado

2015-05-01

Full Text Available Vitamin D3 is a lipophilic micronutrient obtained from the diet (salmon, sardines, mackerel and cod liver oil or by the conversion of 7-dehydrocholesterol on skin after exposure to UVB radiation. This vitamin participates in several cellular processes, contributes to the maintenance of calcium concentrations, acts on phosphorus absorption, and is also related to the development and progression of chronic diseases. In hypertension, it is known that vitamin D3 act on renin-angiotensin-aldosterone system, regulates the gene expression and can induce or attenuate oxidative DNA damage. Vitamin D3 deficiency is present in 30-50% of human population (Pilz et al., 2009, and has been associated with increase of chromosomal instability and DNA damage (Nair-Shalliker; Armstrong; Fenech, 2012. Since experimental and clinical studies have suggested a relationship between vitamin D3 and blood pressure, the aim of this study was to evaluate whether vitamin D3 deficiency or supplementation lead to an increase or decrease in DNA damage, regulates the expression of genes associated with hypertension and changes the systolic blood pressure. Spontaneously hypertensive rats (SHR, used as a model of human essential hypertension, and their normotensive controls (Wistar Kyoto – WKY were fed a control diet (vitamin D3 at 1.000 UI/kg, a deficient diet (vitamin D3 at 0 UI/kg or a supplemented diet (vitamin D3 at 10.000 UI/kg for 12 weeks. DNA damage was assessed by comet assay in cardiac muscle tissue and blood tissue, following the methodology proposed by Singh et al. (1988 and Tice et al. (2000; gene expression of 84 genes was assessed by RT2ProfilerTM PCR Array in cardiac muscle tissue; and systolic blood pressure was measured weekly by a noninvasive method using tail plethysmography. In SHR and WKY rats, vitamin D3 deficiency increased DNA damage in the blood tissue and did not change the DNA damage in cardiac muscle tissue; vitamin D3 supplementation maintained the

Association between antimicrobial resistance and virulence genes in Escherichia coli obtained from blood and faeces

DEFF Research Database (Denmark)

Bagger-Skjøt, Line; Sandvang, Dorthe; Frimodt-Møller, Niels

2007-01-01

Escherichia coli isolates obtained from faeces (n = 85) and blood (n = 123) were susceptibility tested against 17 antimicrobial agents and the presence of 9 virulence genes was determined by PCR. Positive associations between several antimicrobial resistances and 2 VF genes (iutA and traT) were...

Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

Directory of Open Access Journals (Sweden)

Reverter Antonio

2008-09-01

genes. Our guilt-by-association algorithm should be useful for the discovery of additional modifiers of genetic diseases, and more generally, for the ability to associate genes of unknown function to clusters of genes with defined functions allowing for novel biological inference that can be subsequently validated.

Heterotopic expression of class B floral homeotic genes supports a modified ABC model for tulip (Tulipa gesneriana).

Science.gov (United States)

Kanno, Akira; Saeki, Hiroshi; Kameya, Toshiaki; Saedler, Heinz; Theissen, Günter

2003-07-01

In higher eudicotyledonous angiosperms the floral organs are typically arranged in four different whorls, containing sepals, petals, stamens and carpels. According to the ABC model, the identity of these organs is specified by floral homeotic genes of class A, A+B, B+C and C, respectively. In contrast to the sepal and petal whorls of eudicots, the perianths of many plants from the Liliaceae family have two outer whorls of almost identical petaloid organs, called tepals. To explain the Liliaceae flower morphology, van Tunen et al. (1993) proposed a modified ABC model, exemplified with tulip. According to this model, class B genes are not only expressed in whorls 2 and 3, but also in whorl 1. Thus the organs of both whorls 1 and 2 express class A plus class B genes and, therefore, get the same petaloid identity. To test this modified ABC model we have cloned and characterized putative class B genes from tulip. Two DEF- and one GLO-like gene were identified, named TGDEFA, TGDEFB and TGGLO. Northern hybridization analysis showed that all of these genes are expressed in whorls 1, 2 and 3 (outer and inner tepals and stamens), thus corroborating the modified ABC model. In addition, these experiments demonstrated that TGGLO is also weakly expressed in carpels, leaves, stems and bracts. Gel retardation assays revealed that TGGLO alone binds to DNA as a homodimer. In contrast, TGDEFA and TGDEFB cannot homodimerize, but make heterodimers with PI. Homodimerization of GLO-like protein has also been reported for lily, suggesting that this phenomenon is conserved within Liliaceae plants or even monocot species.

Cloning of the cDNA for a human homologue of the Drosophila white gene and mapping to chromosome 21q22.3.

OpenAIRE

Chen, H.; Rossier, C.; Lalioti, M. D.; Lynn, A.; Chakravarti, A.; Perrin, G.; Antonarakis, S. E.

1996-01-01

In an effort to contribute to the transcript map of human chromosome 21 and the understanding of the pathophysiology of trisomy 21, we have used exon trapping to identify fragments of chromosome 21 genes. Two trapped exons, from pools of chromosome 21-specific cosmids, showed homology to the Drosophila white (w) gene. We subsequently cloned the corresponding cDNA for a human homologue of the Drosophila w gene (hW) from human retina and fetal brain cDNA libraries. The gene belongs to the ATP-b...

PROXIMATE AND ELEMENTAL COMPOSITION OF WHITE GRUBS

African Journals Online (AJOL)

DR. AMINU

This study determined the proximate and mineral element composition of whole white grubs using standard methods of analysis. ... and 12.75 ± 3.65% respectively. Mineral contents of white grub in terms of relative concentration .... of intracellular Ca, bone mineralization, blood coagulation, and plasma membrane potential ...

Differential peripheral blood gene expression profile based on Her2 expression on primary tumors of breast cancer patients.

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Oana Tudoran

Full Text Available Breast cancer prognosis and treatment is highly dependent on the molecular features of the primary tumors. These tumors release specific molecules into the environment that trigger characteristic responses into the circulatory cells. In this study we investigated the expression pattern of 84 genes known to be involved in breast cancer signaling in the peripheral blood of breast cancer patients with ER-, PR- primary tumors. The patients were grouped according to Her2 expression on the primary tumors in Her2+ and Her2- cohorts. Transcriptional analysis revealed 15 genes to be differentially expressed between the two groups highlighting that Her2 signaling in primary tumors could be associated with specific blood gene expression. We found CCNA1 to be up-regulated, while ERBB2, RASSF1, CDH1, MKI67, GATA3, GLI1, SFN, PTGS2, JUN, NOTCH1, CTNNB1, KRT8, SRC, and HIC1 genes were down-regulated in the blood of triple negative breast cancer patients compared to Her2+ cohort. IPA network analysis predicts that the identified genes are interconnected and regulate each other. These genes code for cell cycle regulators, cell adhesion molecules, transcription factors or signal transducers that modulate immune signaling, several genes being also associated with cancer progression and treatment response. These results indicate an altered immune signaling in the peripheral blood of triple negative breast cancer patients. The involvement of the immune system is necessary in favorable treatment response, therefore these results could explain the low response rates observed for triple negative breast cancer patients.

A whole-blood transcriptome meta-analysis identifies gene expression signatures of cigarette smoking

NARCIS (Netherlands)

Huan, T. (Tianxiao); R. Joehanes (Roby); C. Schurmann (Claudia); K. Schramm (Katharina); L.C. Pilling (Luke); M.J. Peters (Marjolein); R. Mägi (Reedik); D.L. Demeo (Dawn L.); G.T. O'Connor (George); L. Ferrucci (Luigi); A. Teumer (Alexander); G. Homuth (Georg); R. Biffar (Reiner); U. Völker (Uwe); C. Herder (Christian); M. Waldenberger (Melanie); A. Peters (Annette); S. Zeilinger (Sonja); A. Metspalu (Andres); A. Hofman (Albert); A.G. Uitterlinden (André); D.G. Hernandez (Dena); A. Singleton (Andrew); S. Bandinelli (Stefania); P.J. Munson (Peter); H. Lin (Honghuang); E.J. Benjamin (Emelia); T. Esko (Tõnu); H.J. Grabe (Hans Jörgen); H. Prokisch (Holger); J.B.J. van Meurs (Joyce); D. Melzer (David); D. Levy (Daniel)

2016-01-01

textabstractCigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and smoking-related diseases. We performed a metaanalysis of transcriptome-wide gene expression using whole

Isolation of laccase gene-specific sequences from white rot and brown rot fungi by PCR.

Science.gov (United States)

D'Souza, T M; Boominathan, K; Reddy, C A

1996-01-01

Degenerate primers corresponding to the consensus sequences of the copper-binding regions in the N-terminal domains of known basidiomycete laccases were used to isolate laccase gene-specific sequences from strains representing nine genera of wood rot fungi. All except three gave the expected PCR product of about 200 bp. Computer searches of the databases identified the sequence of each of the PCR products analyzed as a laccase gene sequence, suggesting the specificity of the primers. PCR products of the white rot fungi Ganoderma lucidum, Phlebia brevispora, and Trametes versicolor showed 65 to 74% nucleotide sequence similarity to each other; the similarity in deduced amino acid sequences was 83 to 91%. The PCR products of Lentinula edodes and Lentinus tigrinus, on the other hand, showed relatively low nucleotide and amino acid similarities (58 to 64 and 62 to 81%, respectively); however, these similarities were still much higher than when compared with the corresponding regions in the laccases of the ascomycete fungi Aspergillus nidulans and Neurospora crassa. A few of the white rot fungi, as well as Gloeophyllum trabeum, a brown rot fungus, gave a 144-bp PCR fragment which had a nucleotide sequence similarity of 60 to 71%. Demonstration of laccase activity in G. trabeum and several other brown rot fungi was of particular interest because these organisms were not previously shown to produce laccases. PMID:8837429

Office and Home Blood Pressures as Determinants of Electrocardiographic Left Ventricular Hypertrophy Among Black Nigerians Compared With White Flemish.

Science.gov (United States)

Odili, Augustine N; Thijs, Lutgarde; Yang, Wen-Yi; Ogedengbe, John O; Nwegbu, Maxwell M; Jacobs, Lotte; Wei, Fang-Fei; Feng, Ying-Mei; Zhang, Zhen-Yu; Kuznetsova, Tatiana; Nawrot, Tim S; Staessen, Jan A

2017-11-01

The association of electrocardiographic left ventricular hypertrophy (ECG-LVH) with blood pressure (BP) in Blacks living in sub-Saharan Africa remains poorly documented. In 225 Black Nigerians and 729 White Flemish, we analyzed QRS voltages and voltage-duration products and 12 criteria diagnostic of ECG-LVH in relation to office BP (mean of 5 consecutive readings) and home BP (duplicate morning and evening readings averaged over 1 week). In multivariable analyses, QRS voltage and voltage-duration indexes were generally higher in Blacks than Whites. By using any of 12 criteria, ECG-LVH was more prevalent among Black than White men (54.4% vs. 36.0%) with no ethnic difference among women (17.1%). Precordial voltages and voltage-duration products increased with office and home systolic BP (SBP), and increases were up to 3-fold steeper in Blacks. In Blacks vs. Whites, increases in the Sokolow-Lyon voltage associated with a 10-mm Hg higher SBP were 0.18 mV (95% confidence interval [CI], 0.09-0.26) vs. 0.06 mV (0.02-0.09) and 0.17 mV (0.07-0.28) vs. 0.11 mV (CI, 0.07-0.15) for office and home BP, respectively, with a significant ethnic gradient (P office and home BP in Blacks than Whites. Associations of ECG voltages and voltage-duration products and risk of ECG-LVH with BP are steeper in Black Nigerians compared with a White reference population. In resource-poor settings of sub-Saharan Africa, the ECG in combination with office and home BP is an essential instrument in risk stratification across the entire BP range. © The Author 2017. Published by Oxford University Press on behalf of the American Journal of Hypertension, Ltd.

A Modified Ficoll-Paque Gradient Method for Isolating Mononuclear Cells from the Peripheral and Umbilical Cord Blood of Humans for Biobanks and Clinical Laboratories.

Science.gov (United States)

Jia, Yanjuan; Xu, Hui; Li, Yonghong; Wei, Chaojun; Guo, Rui; Wang, Fang; Wu, Yu; Liu, Jing; Jia, Jing; Yan, Junwen; Qi, Xiaoming; Li, Yuanting; Gao, Xiaoling

2018-04-01

Although the Ficoll-Paque method is classically used to isolate peripheral blood mononuclear cells (PBMCs), modifications in this method are required for a more rapid and economic output for biobanks and clinical laboratories, particularly in developing countries. In this study, we addressed this issue by modifying the Ficoll-Paque method for the isolation of PBMCs or mononuclear cells from the peripheral and the umbilical cord blood of healthy and diseased (infected, anemic, and chronic obstructive pulmonary disease) adult individuals. In the modified method, we initiated the cell isolation process from the buffy coat layer, which appears in the interface between the plasma and sediments after centrifugation, instead of using the whole blood as described in the classic method. Although the PBMC yield by the modified method was about 12% less than in the classic method, the number of PBMCs isolated by the modified method was more than one million, which is enough for different research/diagnostic purposes, such as multi-omics detection. Assessment of cell viability and purity by hematology analyzer and trypan blue showed no significant difference between the viability and purity of the PBMCs isolated by these two methods in almost all groups, except samples from the infected and cord blood groups, where lower PBMC purity with higher granulocyte contamination were observed. In addition, at delayed processing time points, all parameters for the two methods were decreased in a time-dependent manner, especially at 8, 12, or 24 hours after the sample collection. In summary, the performance of PBMC isolation by the classic and modified methods mainly relies on the PBMC ratio in original samples. The modified method could be preferred for PBMC isolation because of its time and cost savings, especially for the biobanks and clinical laboratories in developing countries.

Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer.

Science.gov (United States)

Neslund-Dudas, Christine; Levin, Albert M; Rundle, Andrew; Beebe-Dimmer, Jennifer; Bock, Cathryn H; Nock, Nora L; Jankowski, Michelle; Datta, Indrani; Krajenta, Richard; Dou, Q Ping; Mitra, Bharati; Tang, Deliang; Rybicki, Benjamin A

2014-05-01

Black men have historically had higher blood lead levels than white men in the U.S. and have the highest incidence of prostate cancer in the world. Inorganic lead has been classified as a probable human carcinogen. Lead (Pb) inhibits delta-aminolevulinic acid dehydratase (ALAD), a gene recently implicated in other genitourinary cancers. The ALAD enzyme is involved in the second step of heme biosynthesis and is an endogenous inhibitor of the 26S proteasome, a master system for protein degradation and a current target of cancer therapy. Using a case-only study design, we assessed potential gene-environment (G × E) interactions between lifetime occupational Pb exposure and 11 tagSNPs within ALAD in black (N = 260) and white (N = 343) prostate cancer cases. Two ALAD tagSNPs in high linkage disequilibrium showed significant interaction with high Pb exposure among black cases (rs818684 interaction odds ratio or IOR = 2.73, 95% CI 1.43-5.22, P = 0.002; rs818689 IOR = 2.20, 95% CI 1.15-4.21, P = 0.017) and an additional tagSNP, rs2761016, showed G × E interaction with low Pb exposure (IOR = 2.08, 95% CI 1.13-3.84, P = 0.019). Further, the variant allele of rs818684 was associated with a higher Gleason grade in those with high Pb exposure among both blacks (OR 3.96, 95% CI 1.01-15.46, P = 0.048) and whites (OR 2.95, 95% CI 1.18-7.39, P = 0.020). Genetic variation in ALAD may modify associations between Pb and prostate cancer. Additional studies of ALAD, Pb, and prostate cancer are warranted and should include black men. Prostate 74:637-646, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Fixation of radioactive cerium-144 on white blood cells. Possibilities for use in physiopathology; Fixation du cerium radioactif ({sup 144}Ce) sur les globules blancs. Possibilites d'emploi en physiopathologie

Energy Technology Data Exchange (ETDEWEB)

Aeberhardt, A [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1958-07-01

From the study of the means of transport of cerium in the blood of various laboratory animals, after intra-venous injection of {sup 144}Ce-{sup 144}Pr without carrier, we have been able to show up the part played by the white cells in the transport of this fission product during its passage in the blood. This observation has led to the study, in vitro, of the methods of cerium fixation on the white cells, with a view to determining the possibilities of using this property for white cell labelling, the methods used up to the present not being entirely satisfactory. Using the method for the separation of the known constituents of the blood proposed by us in 1956, we have studied the cerium fixation under various conditions: - on suspensions of white cells from the rabbit, - on a suspension of human white cells, - on the white cells in whole from the rabbit. (author) [French] L'etude du mode de transport du cerium dans le sang chez differents animaux de laboratoire, apres injection intra-veineuse de {sup 144}Ce-{sup 144}Pr sans entraineur, nous a permis de mettre en evidence le rale des globules blancs dans le transport de ce produit de fission au cours de son passage dans le sang. Cette constatation nous a conduit a etudier, in vitro, les modalites de la fixation du cerium sur les globules blancs afin de preciser les possibilites d'utilisation de cette propriete pour le marquage des globules blancs, les methodes employees jusqu'ici ne donnant pas entiere satisfaction. Disposant de la methode de separation des elements figures du sang que nous avons proposee en 1956, nous avons etudie la fixation du cerium, dans diverses conditions: - sur des suspensions de globules blancs de lapin, - sur une suspension de globules blancs humains, - sur les globules blancs dans le sang total de lapin. (auteur)

Prevalence of the white-coat effect at multiple visits before and during treatment.

NARCIS (Netherlands)

Verberk, W.J.; Kroon, A.A.; Thien, Th.; Lenders, J.W.M.; Montfrans, G.A. van; Smit, A.J.; Leeuw, P.W. de

2006-01-01

OBJECTIVE: To investigate the prevalence and persistence of the white-coat effect (WCE) and white-coat hypertension (WCH) on multiple blood pressure measurement occasions in hypertensive patients with and without treatment. DESIGN: Essential hypertensive patients in whom we took office blood

Prevalence of the white-coat effect at multiple visits before and during treatment

NARCIS (Netherlands)

Verberk, Willem J.; Kroon, Abraham A.; Thien, Theo; Lenders, Jacques W. M.; van Montfrans, Gert A.; Smit, Andries J.; de Leeuw, Peter W.

2006-01-01

OBJECTIVE: To investigate the prevalence and persistence of the white-coat effect (WCE) and white-coat hypertension (WCH) on multiple blood pressure measurement occasions in hypertensive patients with and without treatment. DESIGN: Essential hypertensive patients in whom we took office blood

Degradation of endogenous and exogenous genes of genetically modified rice with Cry1Ab during food processing.

Science.gov (United States)

Zhang, Wei; Xing, Fuguo; Selvaraj, Jonathan Nimal; Liu, Yang

2014-05-01

In order to assess the degradation of endogenous and exogenous genes during food processing, genetically modified rice with Cry1Ab was used as raw material to produce 4 processed foods: steamed rice, rice noodles, rice crackers, and sweet rice wine. The results showed various processing procedures caused different degrees of degradation of both endogenous and exogenous genes. During the processing of steamed rice and rice noodles, the procedures were so mild that only genes larger than 1500 bp were degraded, and no degradation of NOS terminator and Hpt gene was detected. For rice crackers, frying was the most severe procedure, followed by microwaving, baking, boiling, 1st drying, and 2nd drying. For sweet rice wine, fermentation had more impact on degradation of genes than the other processing procedures. All procedures in this study did not lead to degradation of genes to below 200 bp, except for NOS terminator. In the case of stability of the genes studied during processing of rice crackers and sweet rice wine, SPS gene was the most, followed by the Cry1Ab gene, Hpt gene, Pubi promoter, and NOS terminator. In our study, we gained some information about the degradation of endogenous and exogenous genes during 4 foods processing, compared the different stabilities between endogenous and exogenous genes, and analyzed different effects of procedure on degradation of genes. In addition, the fragments of endogenous and exogenous genes about 200 bp could be detected in final products, except NOS terminator. As a result, we provided some base information about risk assessment of genetically modified (GM) food and appropriate length of fragment to detect GM component in processed foods. © 2014 Institute of Food Technologists®

Short-term variability and nocturnal decline in ambulatory blood pressure in normotension, white-coat hypertension, masked hypertension and sustained hypertension: a population-based study of older individuals in Spain.

Science.gov (United States)

Gijón-Conde, Teresa; Graciani, Auxiliadora; López-García, Esther; Guallar-Castillón, Pilar; García-Esquinas, Esther; Rodríguez-Artalejo, Fernando; Banegas, José R

2017-06-01

Blood pressure (BP) variability and nocturnal decline in blood pressure are associated with cardiovascular outcomes. However, little is known about whether these indexes are associated with white-coat and masked hypertension. We performed a cross-sectional analysis of 1047 community-dwelling individuals aged ⩾60 years in Spain in 2012. Three observer-measured home BPs and 24-h ambulatory blood pressure monitoring (ABPM) were performed under standardized conditions. BP variability was defined as BP s.d. and coefficient of variation. Differences in BP variability and nocturnal BP decrease between groups were adjusted for sociodemographic and clinical covariates using generalized linear models. Of the cohort, 21.7% had white-coat hypertension, 7.0% had masked hypertension, 21.4% had sustained hypertension, and 49.9% were normotensive. Twenty-four hour, daytime and night-time systolic BP s.d. and coefficients of variation were significantly higher in subjects with white-coat hypertension than those with normotension (Pcoat hypertension than in those with normotension (Pcoat hypertension group and lowest in the masked hypertension group in all patients and untreated patients (Pcoat hypertension, 78.1% of subjects with masked hypertension, and 72.2% of subjects with sustained hypertension (Pcoat hypertension and blunted nocturnal BP decrease was observed more frequently in subjects with masked hypertension. These findings may help to explain the reports of increased cardiovascular risk in patients with white-coat hypertension and poor prognosis in those with masked hypertension, highlighting the importance of ABPM.

Connexin 43 Gene Therapy Delivered by Polymer-Modified Salmonella in Murine Tumor Models

Directory of Open Access Journals (Sweden)

Wei-Kuang Wang

2014-04-01

Full Text Available The use of preferentially tumor-targeting bacteria as vectors is one of the most innovative approaches for the treatment of cancer. This method is based on the observation that some obligate or facultative anaerobic bacteria are capable of selectively multiplying in tumors and inhibiting their growth. Previously, we found that the tumor-targeting efficiency of Salmonella could be modulated by modifying the immune response to these bacteria by coating them with poly(allylamine hydrochloride (PAH, and these organisms are designated PAH-S.C. (S. choleraesuis. PAH can provide a useful platform for the chemical modification of Salmonella, perhaps by allowing a therapeutic gene to bind to tumor-targeting Salmonella. This study aimed to investigate the benefits of the use of PAH-S.C. for gene delivery. To evaluate this modulation, the invasion activity and gene transfer of DNA-PAH-S.C. were measured in vitro and in vivo. Treatment with PAH-S.C. carrying a tumor suppressor gene (connexin 43 resulted in inhibition of tumor growth, which suggested that tumor-targeted gene therapy using PAH-S.C. carrying a therapeutic gene could exert antitumor activities. This technique represents a promising strategy for the treatment of tumors.

Comparative Transcriptome Analysis of Mink (Neovison vison) Skin Reveals the Key Genes Involved in the Melanogenesis of Black and White Coat Colour.

Science.gov (United States)

Song, Xingchao; Xu, Chao; Liu, Zongyue; Yue, Zhigang; Liu, Linling; Yang, Tongao; Cong, Bo; Yang, Fuhe

2017-09-29

Farmed mink (Neovison vison) is one of the most important fur-bearing species worldwide, and coat colour is a crucial qualitative characteristic that contributes to the economic value of the fur. To identify additional genes that may play important roles in coat colour regulation, Illumina/Solexa high-throughput sequencing technology was used to catalogue the global gene expression profiles in mink skin with two different coat colours (black and white). RNA-seq analysis indicated that a total of 12,557 genes were differentially expressed in black versus white minks, with 3,530 genes up-regulated and 9,027 genes down-regulated in black minks. Significant differences were not observed in the expression of MC1R and TYR between the two different coat colours, and the expression of ASIP was not detected in the mink skin of either coat colour. The expression levels of KITLG, LEF1, DCT, TYRP1, PMEL, Myo5a, Rab27a and SLC7A11 were validated by qRT-PCR, and the results were consistent with RNA-seq analysis. This study provides several candidate genes that may be associated with the development of two coat colours in mink skin. These results will expand our understanding of the complex molecular mechanisms underlying skin physiology and melanogenesis in mink and will provide a foundation for future studies.

Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels

Directory of Open Access Journals (Sweden)

Morón Francisco J

2007-01-01

Full Text Available Abstract Background Genes implicated in common complex disorders such as obesity, type 2 diabetes mellitus (T2DM or cardiovascular diseases are not disease specific, since clinically related disorders also share genetic components. Cysteine protease Calpain 10 (CAPN10 has been associated with T2DM, hypertension, hypercholesterolemia, increased body mass index (BMI and polycystic ovary syndrome (PCOS, a reproductive disorder of women in which isunlin resistance seems to play a pathogenic role. The calpain 5 gene (CAPN5 encodes a protein homologue of CAPN10. CAPN5 has been previously associated with PCOS by our group. In this new study, we have analysed the association of four CAPN5 gene variants(rs948976A>G, rs4945140G>A, rs2233546C>T and rs2233549G>A with several cardiovascular risk factors related to metabolic syndrome in general population. Methods Anthropometric measurements, blood pressure, insulin, glucose and lipid profiles were determined in 606 individuals randomly chosen from a cross-sectional population-based epidemiological survey in the province of Segovia in Central Spain (Castille, recruited to investigate the prevalence of anthropometric and physiological parameters related to obesity and other components of the metabolic syndrome. Genotypes at the four polymorphic loci in CAPN5 gene were detected by polymerase chain reaction (PCR. Results Genotype association analysis was significant for BMI (p ≤ 0.041, diastolic blood pressure (p = 0.015 and HDL-cholesterol levels (p = 0.025. Different CAPN5 haplotypes were also associated with diastolic blood pressure (DBP (0.0005 ≤ p ≤ 0.006 and total cholesterol levels (0.001 ≤ p ≤ 0.029. In addition, the AACA haplotype, over-represented in obese individuals, is also more frequent in individuals with metabolic syndrome defined by ATPIII criteria (p = 0.029. Conclusion As its homologue CAPN10, CAPN5 seems to influence traits related to increased risk for cardiovascular diseases. Our

Relationship between diurnal blood pressure and renal histopathological changes in white coat hypertension.

Science.gov (United States)

Tatar, Erhan; Uslu, Adam; Tasli, Funda; Karatas, Murat

2017-08-01

Multiple epidemiological studies have clearly demonstrated the macrovascular risks associated with white coat hypertension (WCH) or sustained hypertension (SH). In patients with WCH, there is no literature available on renal histopathological changes and that on blood pressure pattern and native kidney outcome is scant. We aimed to clarify the relationship between blood pressure variables and pathological features of kidney biopsies in living kidney donors with WCH. This cross-sectional study included living kidney donors with WCH (n = 10) and SH (n = 10), and 20 healthy kidney donors with similar demographic features (control group). Kidney allograft biopsy samples were obtained during transplantation and chronic glomerular, vascular and tubulointertitial changes were semiquantitatively scored according to the Banff classification. The mean age of the 20 hypertensive subjects (Group 1) and controls (Group 2) was 59.3 ± 8.5 versus 59.6 ± 7.6 years and almost half were female. There was no difference in renal function parameters between the groups; however, kidney histopathology in Group 1 was worse than Group 2 with a chronicity index of 2.80 ± 1.67 versus 1.75 ± 1.16 (p = 0.02). There was no difference between histopathological scores of patients with WCH or SH (chronicity index: 2.60 ± 1.43 vs. 2.70 ± 1.70, p = 0.88). Night-to-day mean arterial pressure (MAP) ratio was significantly associated with chronicity index in patients with WCH. Moreover, WCH patients with non-dipper hypertensive pattern had a worse chronicity index. Significant histopathological alterations in the kidney were observed in patients with WCH and SH, and were accentuated in WCH patients with non-dipper blood pressure pattern.

Next generation semiconductor based-sequencing of a nutrigenetics target gene (GPR120) and association with growth rate in Italian Large White pigs.

Science.gov (United States)

Fontanesi, Luca; Bertolini, Francesca; Scotti, Emilio; Schiavo, Giuseppina; Colombo, Michela; Trevisi, Paolo; Ribani, Anisa; Buttazzoni, Luca; Russo, Vincenzo; Dall'Olio, Stefania

2015-01-01

The GPR120 gene (also known as FFAR4 or O3FAR1) encodes for a functional omega-3 fatty acid receptor/sensor that mediates potent insulin sensitizing effects by repressing macrophage-induced tissue inflammation. For its functional role, GPR120 could be considered a potential target gene in animal nutrigenetics. In this work we resequenced the porcine GPR120 gene by high throughput Ion Torrent semiconductor sequencing of amplified fragments obtained from 8 DNA pools derived, on the whole, from 153 pigs of different breeds/populations (two Italian Large White pools, Italian Duroc, Italian Landrace, Casertana, Pietrain, Meishan, and wild boars). Three single nucleotide polymorphisms (SNPs), two synonymous substitutions and one in the putative 3'-untranslated region (g.114765469C > T), were identified and their allele frequencies were estimated by sequencing reads count. The g.114765469C > T SNP was also genotyped by PCR-RFLP confirming estimated frequency in Italian Large White pools. Then, this SNP was analyzed in two Italian Large White cohorts using a selective genotyping approach based on extreme and divergent pigs for back fat thickness (BFT) estimated breeding value (EBV) and average daily gain (ADG) EBV. Significant differences of allele and genotype frequencies distribution was observed between the extreme ADG-EBV groups (P < 0.001) whereas this marker was not associated with BFT-EBV.

Prevalence of the white-coat effect at multiple visits before and during treatment

NARCIS (Netherlands)

Verberk, Willem J.; Kroon, Abraham A.; Thien, Theo; Lenders, Jacques W. M.; van Montfrans, Gert A.; Smit, Andries J.; de Leeuw, Peter W.

2006-01-01

Objective To investigate the prevalence and persistence of the white-coat effect (WCE) and white-coat hypertension (WCH) on multiple blood pressure measurement occasions in hypertensive patients with and without treatment. Design Essential hypertensive patients in whom we took office blood pressure

Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

NARCIS (Netherlands)

Osorio, A.; Milne, R. L.; Alonso, R.; Pita, G.; Peterlongo, P.; Teulé, A.; Nathanson, K. L.; Domchek, S. M.; Rebbeck, T.; Lasa, A.; Konstantopoulou, I.; Hogervorst, F. B.; Verhoef, S.; van Dooren, M. F.; Jager, A.; Ausems, M. G. E. M.; Aalfs, C. M.; van Asperen, C. J.; Vreeswijk, M.; Waisfisz, Q.; van Roozendaal, C. E.; Ligtenberg, M. J.; Easton, D. F.; Peock, S.; Cook, M.; Oliver, C. T.; Frost, D.; Curzon, B.; Evans, D. G.; Lalloo, F.; Eeles, R.; Izatt, L.; Davidson, R.; Adlard, J.; Eccles, D.; Ong, K.-r; Douglas, F.; Downing, S.; Brewer, C.; Walker, L.; Nevanlinna, H.; Aittomäki, K.; Couch, F. J.; Fredericksen, Z.; Lindor, N. M.; Godwin, A.; Isaacs, C.; Caligo, M. A.; Loman, N.; Jernström, H.; Barbany-Bustinza, G.; Liljegren, A.; Ehrencrona, H.; Stenmark-Askmalm, M.; Feliubadaló, L.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Bonanni, B.; Fortuzzi, S.; Johannsson, O. T.; Chenevix-Trench, G.; Chen, X.-C.; Beesley, J.; Spurdle, A. B.; Sinilnikova, O. M.; Healey, S.; McGuffog, L.; Antoniou, A. C.; Brunet, J.; Radice, P.; Benítez, J.; Hogervorst, F. B. L.; Verheus, M.; van 't Veer, L. J.; van Leeuwen, F. E.; Rookus, M. A.; Collée, M.; van den Ouweland, A. M. W.; Hooning, M. J.; Tilanus-Linthorst, M. M. A.; Seynaeve, C.; Wijnen, J. T.; Vreeswijk, M. P.; Tollenaar, R. A.; Devilee, P.; Hoogerbrugge, N.; Ausems, M. G.; van der Luijt, R. B.; van Os, T. A.; Gille, J. J. P.; Meijers-Heijboer, H. E. J.; Gomez-Garcia, E. B.; Blok, Marinus J.; Caanen, B.; Oosterwijk, J. C.; van der Hout, A. H.; Mourits, M. J.; Vasen, H. F.; Peock, Susan; Cook, Margaret; Oliver, Clare; Frost, Debra; Miedzybrodzka, Zosia; Gregory, Helen; Morrison, Patrick; Jeffers, Lisa; Cole, Trevor; McKeown, Carole; Ong, Kai-Ren; Hoffman, Jonathan; Donaldson, Alan; Paterson, Joan; Downing, Sarah; Taylor, Amy; Murray, Alexandra; Rogers, Mark T.; McCann, Emma; Kennedy, M. John; Barton, David; East, South; Porteous, Mary; Drummond, Sarah; Brewer, Carole; Kivuva, Emma; Searle, Anne; Goodman, Selina; Hill, Kathryn; Davidson, Rosemarie; Bradshaw, Nicola; Snadden, Lesley; Longmuir, Mark; Watt, Catherine; Gibson, Sarah; Izatt, Louise; Jacobs, Chris; Langman, Caroline; Whaite, Anna; Dorkins, Huw; Barwell, Julian; Adlard, Julian; Chu, Carol; Miller, Julie; Ellis, Ian; Evans, D. Gareth; Lalloo, Fiona; Taylor, Jane; Side, Lucy; Male, Alison; Berlin, Cheryl; Eason, Jacqueline; Collier, Rebecca; Douglas, Fiona; Claber, Oonagh; Walker, Lisa; McLeod, Diane; Halliday, Dorothy; Durell, Sarah; Stayner, Barbara; Eeles, Ros; Shanley, Susan; Rahman, Nazneen; Houlston, Richard; Bancroft, Elizabeth; D'Mello, Lucia; Page, Elizabeth; Ardern-Jones, Audrey; Kohut, Kelly; Wiggins, Jennifer; Castro, Elena; Mitra, Anitra; Robertson, Lisa; Cook, Jackie; Quarrell, Oliver; Bardsley, Cathryn; Hodgson, Shirley; Goff, Sheila; Brice, Glen; Winchester, Lizzie; Eddy, Charlotte; Tripathi, Vishakha; Attard, Virginia; Eccles, Diana; Lucassen, Anneke; Crawford, Gillian; McBride, Donna; Smalley, Sarah; Godwin, A. K.; Karlsson, Per; Nordling, Margareta; Bergman, Annika; Einbeigi, Zakaria; Stenmark- Askmalm, Marie; Liedgren, Sigrun; Borg, Ake; Loman, Niklas; Olsson, Håkan; Kristoffersson, Ulf; Jernström, Helena; Harbst, Katja; Henriksson, Karin; Lindblom, Annika; Arver, Brita; Wachenfeldt, Anna von; Liljegren, Annelie; Barbany-Bustinza, Gisela; Rantala, Johanna; Melin, Beatrice; Grönberg, Henrik; Stattin, Eva-Lena; Emanuelsson, Monica; Ehrencrona, Hans; Rosenquist Brandell, Richard; Dahl, Niklas

2011-01-01

Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation

Development of a blood-based gene expression algorithm for assessment of obstructive coronary artery disease in non-diabetic patients

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Ellis Stephen G

2011-03-01

Full Text Available Abstract Background Alterations in gene expression in peripheral blood cells have been shown to be sensitive to the presence and extent of coronary artery disease (CAD. A non-invasive blood test that could reliably assess obstructive CAD likelihood would have diagnostic utility. Results Microarray analysis of RNA samples from a 195 patient Duke CATHGEN registry case:control cohort yielded 2,438 genes with significant CAD association (p RT-PCR analysis of these 113 genes in a PREDICT cohort of 640 non-diabetic subject samples was used for algorithm development. Gene expression correlations identified clusters of CAD classifier genes which were reduced to meta-genes using LASSO. The final classifier for assessment of obstructive CAD was derived by Ridge Regression and contained sex-specific age functions and 6 meta-gene terms, comprising 23 genes. This algorithm showed a cross-validated estimated AUC = 0.77 (95% CI 0.73-0.81 in ROC analysis. Conclusions We have developed a whole blood classifier based on gene expression, age and sex for the assessment of obstructive CAD in non-diabetic patients from a combination of microarray and RT-PCR data derived from studies of patients clinically indicated for invasive angiography. Clinical trial registration information PREDICT, Personalized Risk Evaluation and Diagnosis in the Coronary Tree, http://www.clinicaltrials.gov, NCT00500617

Assessment of a six gene panel for the molecular detection of circulating tumor cells in the blood of female cancer patients

International Nuclear Information System (INIS)

Obermayr, Eva; Heinze, Georg; Tong, Dan; Zeillinger, Robert; Sanchez-Cabo, Fatima; Tea, Muy-Kheng M; Singer, Christian F; Krainer, Michael; Fischer, Michael B; Sehouli, Jalid; Reinthaller, Alexander; Horvat, Reinhard

2010-01-01

The presence of circulating tumor cells (CTC) in the peripheral blood of cancer patients has been described for various solid tumors and their clinical relevance has been shown. CTC detection based on the analysis of epithelial antigens might be hampered by the genetic heterogeneity of the primary tumor and loss of epithelial antigens. Therefore, we aimed to identify new gene markers for the PCR-based detection of CTC in female cancer patients. Gene expression of 38 cancer cell lines (breast, ovarian, cervical and endometrial) and of 10 peripheral blood mononuclear cell (PBMC) samples from healthy female donors was measured using microarray technology (Applied Biosystems). Differentially expressed genes were identified using the maxT test and the 50% one-sided trimmed maxT-test. Confirmatory RT-qPCR was performed for 380 gene targets using the AB TaqMan ® Low Density Arrays. Then, 93 gene targets were analyzed using the same RT-qPCR platform in tumor tissues of 126 patients with primary breast, ovarian or endometrial cancer. Finally, blood samples from 26 healthy women and from 125 patients (primary breast, ovarian, cervical, or endometrial cancer, and advanced breast cancer) were analyzed following OncoQuick enrichment and RNA pre-amplification. Likewise, hMAM and EpCAM gene expression was analyzed in the blood of breast and ovarian cancer patients. For each gene, a cut-off threshold value was set at three standard deviations from the mean expression level of the healthy controls to identify potential markers for CTC detection. Six genes were over-expressed in blood samples from 81% of patients with advanced and 29% of patients with primary breast cancer. EpCAM gene expression was detected in 19% and 5% of patients, respectively, whereas hMAM gene expression was observed in the advanced group (39%) only. Multimarker analysis using the new six gene panel positively identified 44% of the cervical, 64% of the endometrial and 19% of the ovarian cancer patients. The

Microarray and RT-PCR screening for white spot syndrome virus immediate-early genes in cycloheximide-treated shrimp

International Nuclear Information System (INIS)

Liu Wangjing; Chang Yunshiang; Wang Chunghsiung; Kou, Guang-Hsiung; Lo Chufang

2005-01-01

Here, we report for the first time the successful use of cycloheximide (CHX) as an inhibitor to block de novo viral protein synthesis during WSSV (white spot syndrome virus) infection. Sixty candidate IE (immediate-early) genes were identified using a global analysis microarray technique. RT-PCR showed that the genes corresponding to ORF126, ORF242 and ORF418 in the Taiwan isolate were consistently CHX-insensitive, and these genes were designated ie1, ie2 and ie3, respectively. The sequences for these IE genes also appear in the two other WSSV isolates that have been sequenced. Three corresponding ORFs were identified in the China WSSV isolate, but only an ORF corresponding to ie1 was predicted in the Thailand isolate. In a promoter activity assay in Sf9 insect cells using EGFP (enhanced green fluorescence protein) as a reporter, ie1 showed very strong promoter activity, producing higher EGFP signals than the insect Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) ie2 promoter

Is white-coat hypertension a harbinger of increased risk?

Science.gov (United States)

Kollias, Anastasios; Ntineri, Angeliki; Stergiou, George S

2014-09-01

White-coat hypertension is defined by elevated office and normal out-of-office blood pressure (home or ambulatory) in untreated subjects. This condition is common in clinical practice and requires appropriate work-up for detection and management. Many studies have examined the relationship between white-coat hypertension and cardiovascular risk but with marked heterogeneity in the definitions and methodology applied. Thus, the results have been inconsistent leading to confusion in scientific research and clinical practice. Some but not all the relevant studies suggested that white-coat hypertension is associated with subclinical target-organ damage, yet the cross-sectional design of these studies and the fact that these indices are only surrogate end points do not allow firm conclusions to be drawn. In recent years, longitudinal studies have examined the prognostic significance of white-coat hypertension in terms of cardiovascular morbidity and mortality. Most of them indicate that white-coat hypertensive compared with normotensive subjects present a moderate-in most cases not significant-increase in risk. Meta-analyses of raw data from large databases, such as the International Database on Ambulatory blood pressure and Cardiovascular Outcomes (IDACO) and the International Database on HOme blood pressure in relation to Cardiovascular Outcomes (IDHOCO) allowed separate powered analyses in untreated subjects and provided a clearer picture regarding the modest risk associated with white-coat hypertension, especially in the long term. White-coat hypertension is regarded as an intermediate phenotype between normotension and hypertension associated with increased risk of developing sustained hypertension, and therefore requires regular follow-up using nonpharmacological measures.

Ex-Vivo Gene Therapy Using Lentiviral Mediated Gene Transfer Into Umbilical Cord Blood Derived Stem Cells

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Hanieh Jalali

2016-02-01

Full Text Available Background Introduction of therapeutic genes into the injured site of nervous system can be achieved using transplantation of cellular vehicles containing desired gene. To transfer exogenous genes into the cellular vehicles, lentiviral vectors are one of interested vectors because of advantages such high transduction efficiency of dividing and non-dividing cells. Unrestricted somatic stem cells are subclasses of umbilical cord blood derived stem cells which are appreciate candidates to use as cellular vehicles for ex vivo gene therapy of nervous system. Objectives In current study we investigated the effect of lentiviral vector transduction on the neuronal related features of unrestricted somatic stem cells to indicate the probable and unwanted changes related to transduction procedure. Materials and Methods In this experimental study, lentiviral vector containing green fluorescent protein (GFP were transduced into unrestricted somatic stem cells and its effect was investigated with using MTT assay, qPCR and immunohistochemistry techniques. For statistical comparison of real time PCR results, REST software (2009, Qiagen was used. Results Obtained results showed lentiviral vector transduction did not have cytotoxic effects on unrestricted somatic stem cells and did not change neuronal differentiation capacity of them as well the expression of some neuronal related genes and preserved them in multilineage situation. Conclusions In conclusion, we suggested that lentiviral vectors could be proper vectors to transfer therapeutic gene into unrestricted somatic stem cells to provide a cellular vehicle for ex vivo gene therapy of nervous system disorders.

Molecular detection of aminoglycoside-modifying enzyme genes in Acinetobacter baumannii clinical isolates.

Science.gov (United States)

Heidary, Mohsen; Salimi Chirani, Alireza; Khoshnood, Saeed; Eslami, Gita; Atyabi, Seyyed Mohammad; Nazem, Habibollah; Fazilati, Mohammad; Hashemi, Ali; Soleimani, Saleh

2017-06-01

Acinetobacter baumannii is a major opportunistic pathogen in healthcare settings worldwide. In Iran, there are only few reports on the prevalence of aminoglycoside resistance genes among A. baumannii isolates. The aim of this study was to investigate the existence of aminoglycoside-modifying enzyme (AME) genes from A. baumannii strains collected at a university teaching hospital in Iran. One hundred A. baumannii strains were collected between 2014 and 2015 from hospitalized patients at Loghman Hakim Hospital, Tehran, Iran. Antimicrobial susceptibility was determined by disk diffusion method according to the Clinical and Laboratory Standards Institute recommendations. The DNA was extracted using a kit obtained from Bioneer Co. (Korea) and was used as a template for polymerase chain reaction. The most active antimicrobial agent against these strains was colistin. The rate of extended-spectrum cephalosporin resistance was 97%. The aadA1, aadB, aac(6')-Ib, and aac(3)-IIa genes were found in 85%, 77%, 72%, and 68% of A. baumannii isolates, respectively. This study showed a high prevalence rate of AME genes in A. baumannii. This prevalence rate has explained that further aminoglycoside resistance genes may have role in the resistance of clinical isolates of A. baumannii. Therefore, control and treatment of serious infections caused by this opportunistic pathogen should be given more consideration.

Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes

DEFF Research Database (Denmark)

Vinther-Jensen, T; Nielsen, Troels Tolstrup; Budtz-Jørgensen, E

2016-01-01

Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has......-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance...

Dietary methanol regulates human gene activity.

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Anastasia V Shindyapina

Full Text Available Methanol (MeOH is considered to be a poison in humans because of the alcohol dehydrogenase (ADH-mediated conversion of MeOH to formaldehyde (FA, which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD. There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling.

[A comparative study of blood culture conventional method vs. a modified lysis/centrifugation technique for the diagnosis of fungemias].

Science.gov (United States)

Santiago, Axel Rodolfo; Hernández, Betsy; Rodríguez, Marina; Romero, Hilda

2004-12-01

The purpose of this work was to compare the efficacy of blood culture conventional method vs. a modified lysis/centrifugation technique. Out of 450 blood specimens received in one year, 100 where chosen for this comparative study: 60 from patients with AIDS, 15 from leukemic patients, ten from febrile neutropenic patients, five from patients with respiratory infections, five from diabetics and five from septicemic patients. The specimens were processed, simultaneously, according to the above mentioned methodologies with daily inspections searching for fungal growth in order to obtain the final identification of the causative agent. The number (40) of isolates recovered was the same using both methods, which included; 18 Candida albicans (45%), ten Candida spp. (25%), ten Histoplasma capsulatum (25%), and two Cryptococcus neoformans (5%). When the fungal growth time was compared by both methods, growth was more rapid when using the modified lysis/centrifugation technique than when using the conventional method. Statistical analysis revealed a significant difference (pcentrifugation technique showed to be more efficacious than the conventional one, and therefore the implementation of this methodology is highly recommended for the isolation of fungi from blood.

Evidence of inflammatory immune signaling in chronic fatigue syndrome: A pilot study of gene expression in peripheral blood

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Vernon Suzanne D

2008-09-01

Full Text Available Abstract Background Genomic profiling of peripheral blood reveals altered immunity in chronic fatigue syndrome (CFS however interpretation remains challenging without immune demographic context. The object of this work is to identify modulation of specific immune functional components and restructuring of co-expression networks characteristic of CFS using the quantitative genomics of peripheral blood. Methods Gene sets were constructed a priori for CD4+ T cells, CD8+ T cells, CD19+ B cells, CD14+ monocytes and CD16+ neutrophils from published data. A group of 111 women were classified using empiric case definition (U.S. Centers for Disease Control and Prevention and unsupervised latent cluster analysis (LCA. Microarray profiles of peripheral blood were analyzed for expression of leukocyte-specific gene sets and characteristic changes in co-expression identified from topological evaluation of linear correlation networks. Results Median expression for a set of 6 genes preferentially up-regulated in CD19+ B cells was significantly lower in CFS (p = 0.01 due mainly to PTPRK and TSPAN3 expression. Although no other gene set was differentially expressed at p Conclusion Dissection of blood microarray profiles points to B cell dysfunction with coordinated immune activation supporting persistent inflammation and antibody-mediated NK cell modulation of T cell activity. This has clinical implications as the CD19+ genes identified could provide robust and biologically meaningful basis for the early detection and unambiguous phenotyping of CFS.

HPRT gene mutation frequency and the factor of influence in adult peripheral blood lymphocytes

International Nuclear Information System (INIS)

Zhao Jingyong; Zheng Siying; Cui Fengmei; Wang Liuyi; Lao Qinhua; Wu Hongliang

2002-01-01

Objective: To study the HPRT gene loci mutation frequencies and the factor of influence in peripheral blood lymphocytes of adult with ages ranging from 21-50. Methods: HPRT gene mutation frequency (GMf) were examined by the technique of multinuclear cell assay. Relation between GMf and years were fitted with a computer. Results: Relation could be described by the following equation: y = 0.7555 + 0.0440x, r = 0.9829. Smoking has influence on GMf and sex hasn't. Conclusion: HPRT gene mutation frequency increases with increasing of age. Increasing rate is 0.00440% per year