Spelling suggestions: "subject:"biomarkers.""
121 |
Etude du risque de transmission du paludisme le long de la frontière birmano-thaïlandaise par l’utilisation de biomarqueurs spécifiques d’exposition humaine aux piqures d’Anopheles et au Plasmodium / Risk of malaria transmission along the Thailand-Myanmar border by the use of specific biomarker of human exposure to Anopheles bites and Plasmodium sppYa-Umphan, Phubeth 24 November 2017 (has links)
Le long de la frontière entre la Thaïlande et le Myanmar (TMB), le paludisme se caractérise par une forte hétérogénéité de la transmission, une forte prévalence en porteurs sub-microscopiques et par l’émergence de la résistance à l’artémisinine chez Plasmodium falciparum. L'identification précoce des « foyers » infectieux et leurs éliminations sont nécessaires pour contenir la résistance à l'artémisinine. L'objectif de cette thèse était de démontrer l’intérêt d’utiliser des biomarqueurs sérologiques de l'exposition humaine aux piqûres d'anophèles (gSG6-P1) et au Plasmodium (CSP & MSP1-19) pour quantifier le contact homme-vecteur et identifier les foyers résiduels de transmission. Des papiers filtres contenant du sang ont été prélevés sur une cohorte de 2600 personnes suivie tous les 3 mois jusqu'à 18 mois et analysés par dosage immuno-enzymatique (ELISA). Nos résultats ont montré que les niveaux de réponse IgG à l'antigène gSG6-P1 variaient selon le village, la saison et l'âge et étaient positivement corrélés à l'abondance des espèces anophèles et des vecteurs primaires de paludisme. Une association significative et positive a été observée entre la réponse de l'anticorps au gSG6-P1 et le taux d'inoculation entomologique (EIR), démontrant ainsi que l'hétérogénéité de la transmission du paludisme était directement associée à un comportement de piqûre hétérogène. Des études complémentaires ont montré que le biomarqueur salivaire était pertinent pour détecter des variations micro géographiques dans la transmission à P. falciparum. Cela s’est traduit par des chevauchements significatifs entre les foyers infectieux à P. falciparum et ceux à forts répondeurs en anticorps anti-salive d’anopheles (gSG6-P1). Dans l'ensemble, ces résultats indiquent que le biomarqueur salivaire d'Anopheles est prometteur pour les études épidémiologiques et pourrait guider la mise en œuvre d’interventions de lutte antivectorielle « ciblées » afin d'éliminer les foyers résiduels de paludisme. / Malaria along the Thailand-Myanmar border (TMB) displays geographical heterogeneity and is characterized by high prevalence of submicroscopic carriage and the emergence artemisinin resistance in P. falciparum. Timely identification and elimination of remaining P. falciparum transmission “hotspots” is essential to contain artemisinine resistance. The aim of this study was to address the relevance of using serological biomarkers of human exposure to anopheles bites (gSG6-P1) and Plasmodium antigens to identify remaining sources of transmission and to measure spatial and temporal changes in human vector contact along the TMB. Blood spots were collected in filter papers among a cohort of 2600 people followed every 3 months up to 18 months, and used for analysis by enzyme-linked immunosorbent assay (ELISA). Our findings showed that the levels of IgG responses to gSG6-P1 antigen varied according to village, season, and age and were positively associated with the abundance of total Anopheles species and primary malaria vectors. A significant and positive association was noted between the Antibody response to gSG6-P1 and the entomological inoculation rate (EIR) hence demonstrating that heterogeneity in malaria transmission was directly associated with heterogeneous biting behavior. Further investigations showed that salivary biomarker was relevant to detect small scale variations in P. falciparum malaria. This was supported by scan statistics showing that P. falciparum clusters partially overlap the gSG6-P1 clusters. Altogether, these findings indicates Anopheles salivary biomarker as great potential for epidemiological studies and could be useful to guide the implementation of hotspot–targeted vector control interventions with the aim to achieve malaria elimination.
|
122 |
Auswahl und Validierung immunologischer Indikatoren für entzündliche Erkrankungen bei HochleistungsmilchkühenZoldan, Katharina 08 March 2016 (has links)
Die vorliegende Arbeit beschäftigt sich mit der Identifikation neuer immunologischer Indikatoren (Biomarker) für den allgemeinen Gesundheitszustand von Hochleistungsmilchkühen. Diese Biomarker sollen möglichst einfach und schnell mittels eines Stalltests nachweisbar sein, weshalb die gelösten Proteine in der Milch im Fokus standen. Die neuen Biomarker sollten nicht nur Mastitis, sondern vor allem auch Entzündungen außerhalb des Euters anzeigen können. Zu Beginn sollte das Gesamtspektrum an Immunkomponenten erfasst werden, weshalb zunächst auf Proteinexpressionsebene angesetzt wurde. Das schloss die Analyse von vorhandenen Immunzellpopulationen in Blut- und Milchproben ein, um einen Überblick über potentielle Produzenten der immunologischen Indikatoren zu erhalten. Es konnte erstmals Cluster of Differentiation (CD) 25 (alpha-Kette des Interleukin-2-Rezeptors, IL2R) auf bovinen polymorphnukleären, neutrophilen Granulozyten (PMN) aus peripherem Blut nachgewiesen werden. Die Expression (mittlere Fluoreszenzintensität, MFI) von CD25 stieg dabei mit dem Schweregrad der entzündlichen Erkrankung an. Die Ergebnisse konnten auf Transkript- wie auch auf Proteinexpressionsebene bestätigt werden. Gleiche Tendenzen waren auch für Milchzellen erkennbar. In der statistischen Analyse zeigte CD25 auf PMN im peripheren Blut ein hohes Abgrenzungsvermögen für erkrankte Kühe. Die Messung von CD25 auf PMN könnte somit zur Bestimmung des allgemeinen Gesundheitszustandes von Hochleistungsmilchkühen genutzt werden.
|
123 |
Analysis of candidate soluble and cellular biomarkers in patients with axial spondyloarthritis compared to chronic low back pain and healthy controlsBauchiero, Caroline Grace 14 February 2024 (has links)
BACKGROUND: Distinguishing patients with axial spondyloarthritis (axial SpA) from patients with other causes of chronic back pain remains a challenge. The lack of reliable biomarkers contributes to the diagnostic delay in axial SpA. Recently, macrophage migration inhibitory factor (MIF) has been proposed as a candidate diagnostic and prognostic biomarker. MIF is a proinflammatory cytokine that was shown to be upregulated in several autoimmune diseases, including axial SpA. The putative role of CD8+ T cells in the disease process suggests further that serum markers of cytotoxicity might have value as serological biomarkers in axial SpA, and that subpopulations of cytotoxic lymphocytes might deserve attention as candidate cellular biomarkers.
OBJECTIVE: The goal of this study was to compare serum levels of MIF and other candidate serum proteins in patients with axial SpA and controls, and to develop a flow cytometry panel to analyze cytotoxic lymphocyte cell subpopulations in these cohorts, including KIR+CD8+ T cells, Granzyme B+ CD8+ T cells, MAIT cells, and InEx cells.
METHODS: Study subjects were recruited from the Brigham and Women’s Hospital Orthopedic and Arthritis Center. Four cohorts were compared: healthy controls (HC), patients with chronic low back pain (cLBP), axial SpA patients not on a biologic (axSpA/-), and axial SpA patients treated with a TNF inhibitor (axSpA/TNFi). Study subjects were matched for age, sex, and race, when possible. Serum was evaluated using the LEGENDplex Human CD8/NK panel (BioLegend) for thirteen markers including IL-17A, IL-6, TNF, granzyme B, and perforin. CRP and MIF were evaluated by DuoSet ELISA (R&D Systems). A high-dimensional flow cytometry panel was designed to evaluate 14 cell populations of interest.
RESULTS: The severity of back pain in the cLBP controls and axSpA/- patients was comparable (BASDAI Q2 mean 5.0 +/- 1.9 vs. 5.0 +/- 3.0). axSpA/- patients had higher back pain, BASDAI and ASDAS scores than axSpA/TNFi patients consistent with higher disease activity in the biologic naïve group. Serum CRP values were significantly higher in axSpA/- patients compared with HC, cLBP controls, and axSpA/TNFi patients (P= 0.01, P=0.0029, P=0.004 respectively). Serum MIF levels were not statistically different between all four groups (P= 0.8069). Additionally, there were no statistically significant differences between the groups for any of the markers included in the LEGENDplex Human CD8/NK panel. A 32-color staining panel was developed to evaluate cytotoxic cell populations.
CONCLUSION: In contrast to a previous study, we did not find differences in serum MIF levels between axial SpA patients and controls. Of the evaluated serum biomarkers, only CRP values correlated with active axial SpA. We have developed a promising flow cytometry panel that will help analyze subpopulations of cytotoxic cells. This ultimately could shed light on a candidate cellular biomarker. Our results underscore the need for more research into diagnostic biomarkers in axial SpA.
|
124 |
Design and Development of New Chemistry for BiosensingWu, Haiyan January 2017 (has links)
No description available.
|
125 |
Assessment of the Validity, Reliability, and Sensitivity of Fingerstick δ¹³C as an Added Sugar Biomarker in Adolescents: A Controlled Feeding Study ApproachLiu, Sarah Victoria 22 May 2017 (has links)
An estimated 20.5% of adolescents ages 12 – 19 years were obese (≥95th percentile of BMI-for-age) in 2011 – 2014. Consumption of added sugars (AS) has been linked with adverse effects on weight and cardiovascular disease risk factors. Approximately 16% of adolescents’ calories come from AS, of which sugar-sweetened beverages (SSB) are a major contributor. However, the relationship between AS/SSB intake and obesity is controversial, partly due to limitations in self-reported dietary data. Objective dietary intake biomarkers may circumvent this problem. The δ13C biomarker for AS intake is based upon the fact that C4 plants– major source for sugar production in the United States – have elevated δ¹³C values compared to C3 plants, which includes most fruits and vegetables. The δ¹³C value of blood, which is influenced by diet, has been established as a valid, reliable, and sensitive biomarker, but when compared to selfreported AS intake. This investigation evaluated the sensitivity and reliability of the δ13C biomarker, assessed with fingerstick blood samples, in adolescents using a controlled feeding, crossover design. Fingerstick δ¹³C values significantly changed by -0.05‰ and +0.03‰ after subjects completed the 5% and 25% AS diets, respectively (F(1, 30) = 18.828, p < 0.001). High reliability was found between two consecutive fingerstick δ¹³C values on the low (ICC = 0.996) and high (ICC = 0.997) AS diets. Thus, fingerstick δ¹³C may be a sensitive and reliable indicator of AS intake in adolescents. Future investigations should develop an equation to estimate AS intake based on fingerstick δ¹³C / Master of Science
|
126 |
Effects of Physical Activity on the Performance of 24-h Urinary Sucrose and Fructose as a Biomarker of Total Sugars IntakeJanuary 2019 (has links)
abstract: Urinary sucrose and fructose has been suggested as a predictive biomarker of total sugars intake based on research involving UK adults. The purpose of this study was to determine the association between total sugars consumption and 24-hour urinary sucrose and fructose (24uSF) in US adult population and to investigate the effect of physical activity on this association. Fifty seven free-living healthy subjects 20 to 68 years old, participated in a 15-day highly controlled feeding study, consuming their habitual diet, provided by the research metabolic kitchen. Dietary sugars were estimated using Nutrition Data System for Research (NDSR). Subjects collected eight 24-hour urine samples measured for urinary sucrose and fructose. Physical activity was assessed daily using a validated 15-day log that inquired about 38 physical activities across six domains; home activities, transportation, occupation, conditioning, sports and leisure. The mean total sugars intake and added sugars intake of the sample was 112.2 (33.1) g/day and 65.8 (29.0) g/day (9.7%EI), respectively. Significant moderate positive correlation was found between 15-d mean total sugars intake and 8-day mean 24uSF (r = 0.56, p < 0.001). Similarly, added sugars were moderately correlated with 24uSF (r = 0.56, p < 0.001), while no correlation was found between naturally-occurring sugars and 24uSF (r = 0.070, p < 0.001). In a linear multiple regression, total and added sugars each explained 30% of variability in 24uSF (Adjusted R2, p value; total sugars: 0.297, 0.001; added sugars: 0.301, p < 0.001). Physical activity had no effect on the association between dietary and urinary sugars in neither the correlation nor the linear regression analysis. 24uSF can be used as a biomarker for total and added sugars consumption in US adults, although its predictability was weaker compared to findings involving UK adults. No evidence was found showing that physical activity levels affect the association between 24uSF and total sugars intake in US adults. More detailed investigation through future feeding studies including subjects with wide range of sugars intake and of different ethnic/racial backgrounds are needed to better understand the characteristics of the biomarker and its uses. / Dissertation/Thesis / Masters Thesis Nutrition 2019
|
127 |
An untargeted LC-MS investigation of South African children with respiratory chain deficiencies / Leonie VenterVenter, Leonie January 2014 (has links)
Mitochondria are the main site of cellular adenosine triphosphate (ATP) generation which is achieved by a series of multi-subunit complexes and electron carriers which together create the oxidative phosphorylation system (OXPHOS). Whenever a defect in any of the numerous mitochondrial pathways occurs it is commonly referred to as a mitochondrial disorder. Mitochondrial disorders are a heterogeneous group of disorders characterised by impaired energy production and include a wide range of defects of either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) encoded proteins. In cases of dysfunction in the respiratory chain (complex I to IV) it is known to be a respiratory chain deficiency (RCD) which presents a huge challenge for routine diagnosis largely due to the lack of a specific and sensitive biomarker(s). One sure way of confirming the suspicion of a RCD is by performing enzyme analysis on a muscle sample obtained through a biopsy. However, due to the lack of theatre time available to clinicians and the relative large number of false positive patients that are being selected for biopsies, it was decided to develop a biosignature to limit the number of false positive patients from the diagnostic workflow.
An untargeted liquid chromatography mass spectrometry (LC-MS) metabolomics approach was used to investigate RCDs in children from South Africa. Sample preparation, a liquid chromatography time-of-flight mass spectrometry method and data processing methods were standardised. Furthermore the developed methodology made use of reverse phase chromatography in conjunction with positive electrospray ionisation (ESI) and a hydrophilic interaction chromatography (HILIC) in negative electrospray ionisation. Urine samples of 61 patients representing three different experimental groups were analysed. The three experimental groups comprised of patients with respiratory chain deficiencies, clinical referred controls (CRC) and patients suffering from various neuromuscular disorders (NMD). After a variety of data mining steps and statistical analysis a list of 12 features were compiled with the ability to distinguish between patients with RCDs and CRCs. The proposed signature was also tested on the neuromuscular disorder group, but this result indicated that the biosignature performed better when used to differentiate between patients with RCDs and CRCs, since the model was designed with this purpose. An alternative validation study is required to identify the features found with this proposed biosignature, to ensure that this biosignature can be practically implemented as a non-invasive screening method. / MSc (Chemistry), North-West University, Potchefstroom Campus, 2014
|
128 |
An untargeted LC-MS investigation of South African children with respiratory chain deficiencies / Leonie VenterVenter, Leonie January 2014 (has links)
Mitochondria are the main site of cellular adenosine triphosphate (ATP) generation which is achieved by a series of multi-subunit complexes and electron carriers which together create the oxidative phosphorylation system (OXPHOS). Whenever a defect in any of the numerous mitochondrial pathways occurs it is commonly referred to as a mitochondrial disorder. Mitochondrial disorders are a heterogeneous group of disorders characterised by impaired energy production and include a wide range of defects of either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) encoded proteins. In cases of dysfunction in the respiratory chain (complex I to IV) it is known to be a respiratory chain deficiency (RCD) which presents a huge challenge for routine diagnosis largely due to the lack of a specific and sensitive biomarker(s). One sure way of confirming the suspicion of a RCD is by performing enzyme analysis on a muscle sample obtained through a biopsy. However, due to the lack of theatre time available to clinicians and the relative large number of false positive patients that are being selected for biopsies, it was decided to develop a biosignature to limit the number of false positive patients from the diagnostic workflow.
An untargeted liquid chromatography mass spectrometry (LC-MS) metabolomics approach was used to investigate RCDs in children from South Africa. Sample preparation, a liquid chromatography time-of-flight mass spectrometry method and data processing methods were standardised. Furthermore the developed methodology made use of reverse phase chromatography in conjunction with positive electrospray ionisation (ESI) and a hydrophilic interaction chromatography (HILIC) in negative electrospray ionisation. Urine samples of 61 patients representing three different experimental groups were analysed. The three experimental groups comprised of patients with respiratory chain deficiencies, clinical referred controls (CRC) and patients suffering from various neuromuscular disorders (NMD). After a variety of data mining steps and statistical analysis a list of 12 features were compiled with the ability to distinguish between patients with RCDs and CRCs. The proposed signature was also tested on the neuromuscular disorder group, but this result indicated that the biosignature performed better when used to differentiate between patients with RCDs and CRCs, since the model was designed with this purpose. An alternative validation study is required to identify the features found with this proposed biosignature, to ensure that this biosignature can be practically implemented as a non-invasive screening method. / MSc (Chemistry), North-West University, Potchefstroom Campus, 2014
|
129 |
Cellular prostatic acid phosphatase (cPAcP) serves as a useful biomarker of histone deacetylase (HDAC) inhibitors in prostate cancer cell growth suppressionChou, Yu-Wei, Lin, Fen-Fen, Muniyan, Sakthivel, Lin, Frank C., Chen, Ching-Shih, Wang, Jue, Huang, Chao-Cheng, Lin, Ming-Fong January 2015 (has links)
BACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed solid tumor and the second leading cancer death in the United States, and also one of the major cancer-related deaths in Chinese. Androgen deprivation therapy (ADT) is the first line treatment for metastatic PCa. PCa ultimately relapses with subsequent ADT treatment failure and becomes castrate-resistant (CR). It is important to develop effective therapies with a surrogate marker towards CR PCa. METHOD: Histone deacetylase (HDAC) inhibitors were examined to determine their effects in androgen receptor (AR)/ cellular prostatic acid phosphatase (cPAcP)-positive PCa cells, including LNCaP C-33, C-81, C4-2 and C4-2B and MDA PCa2b androgen-sensitive and androgen-independent cells, and AR/cPAcP-negative PCa cells, including PC-3 and DU 145 cells. Cell growth was determined by cell number counting. Western blot analyses were carried out to determine AR, cPAcP and PSA protein levels. RESULTS: cPAcP protein level was increased by HDAC inhibitor treatment. Valproic acid, a HDAC inhibitor, suppressed the growth of AR/cPAcP-positive PCa cells by over 50% in steroid-reduced conditions, higher than on AR/cPAcP-negative PCa cells. Further, HDAC inhibitor pretreatments increased androgen responsiveness as demonstrated by PSA protein level quantitation. CONCLUSION: Our results clearly demonstrate that HDAC inhibitors can induce cPAcP protein level, increase androgen responsiveness, and exhibit higher inhibitory activities on AR/cPAcP-positive PCa cells than on AR/cPAcP-negative PCa cells. Upon HDAC inhibitor pretreatment, PSA level was greatly elevated by androgens. This data indicates the potential clinical importance of cPAcP serving as a useful biomarker in the identification of PCa patient sub-population suitable for HDAC inhibitor treatment.
|
130 |
Evaluation of biomarkers for testicular toxicityElkin, Naomi D. January 2010 (has links)
Non-clinical safety assessment is essential during the drug development process in the pharmaceutical industry, and involves numerous, detailed in vitro and in vivo toxicology tests (general, reproductive and genetic), and safety pharmacology studies. The testis is a common organ for adverse drug effects leading to attrition of potential compounds. It would, therefore, be useful to detect testicular toxicity as early as possible in the drug development process. Histopathology is the standard method for assessing testis toxicity, but a biomarker for ‘early warning’ detection of testicular toxicity would be far more useful in non-clinical toxicology studies. The aim of this thesis was to evaluate the feasibility of this approach. It is thought that proteins can leak from seminiferous tubules into testicular interstitial fluid following testicular damage, due to either loss of integrity of the blood-testis barrier (BTB) or germ cell damage. A potential biomarker protein could, therefore, leak out of seminiferous tubules into interstitial fluid and then into blood following toxicological insult to the testis. A suitable biomarker protein must be testis specific, abundant, and not normally be present in blood. It may also need to have a low molecular weight. To investigate if proteins do leak out of seminiferous tubules following testicular damage, three known testicular toxicants which affect different aspects of the testis were used; cadmium chloride causes disruption to the blood-testis barrier and spermatogenesis, methoxyacetic acid (MAA) specifically causes a loss of pachytene spermatocytes, and 1,3-dinitrobenzene (DNB) causes Sertoli cell vacuolation and subsequent germ cell disruption. Adult male Wistar rats were treated with various doses of these toxicants to give mild and moderate responses. Samples were collected 24 hours later. Testicular damage was investigated by immunohistochemistry for well-known germ cell markers (DAZL, VASA) and using a general antibody to seminiferous tubule proteins. The integrity of the BTB was evaluated using immunofluorescent co-localisation of occludin, ZO-1, claudin-11, N-cadherin and β-catenin, and a biotin tracer. Protein leakage was investigated using analysis of interstitial fluid samples by 1D gel electrophoresis and staining with Coomassie-based dye or Western blotting for germ cell proteins and with the general antibody to seminiferous tubule proteins. Protein leakage from seminiferous tubules into interstitial fluid was observed with high dose cadmium chloride treatment. This was coincident with a loss of integrity of the BTB. No leakage was observed with MAA treatment which caused a specific loss of pachytene spermatocytes, or DNB which caused Sertoli cell vacuolation. With both treatments the BTB did not appear to be damaged suggesting that protein leakage occurs only following loss of integrity of the BTB. This was further investigated using treatments reported to specifically disrupt the BTB, namely intra-testicular administration of glycerol or transforming growth factor-β3, with samples collected 48 hours later. The damage caused was very localised, although BTB disruption with glycerol treatment caused some protein leakage. The presence of germ cell proteins in interstitial fluid samples before and after the development of the BTB during normal development was also evaluated, although most proteins of interest were not expressed in germ cells of the immature testis before BTB formation. Finally, five potential biomarker candidate proteins (ADAM3, Calpastatin, DAZL, FABP9, VASA) were selected and investigated using samples from the testicular toxicant studies. Smaller molecular weight proteins were thought to be more likely to leak out of seminiferous tubules, however, VASA, a large molecular protein (76kDa) was shown to leak into interstitial fluid following high dose cadmium chloride treatment. However, FABP9 (low molecular weight) was found to be the most promising biomarker for loss of BTB integrity. The results suggest that a biomarker could only be detected if there is a loss of integrity of the BTB and severe disruption of spermatogenesis, thus conferring no real advantage over present histopathology-based toxicity evaluations. Therefore, an automated immunohistochemistry and image analysis method was investigated as a refined method for detection of testicular toxicity at the end of a toxicology study, and shown to have promise.
|
Page generated in 0.0541 seconds