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Blight, Keril Jaye. "Studies of the hepatic expression of hepatitis C virus markers /." Title page, contents and abstract only, 1994. http://web4.library.adelaide.edu.au/theses/09PH/09phb6482.pdf.
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Thesis (Ph. D.)--University of Adelaide, Dept. of Microbiology and Immunology, 1995?Includes five copies of author's previously published articles in back pocket. Includes bibliographical references (leaves 120-142).
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Lexander, Helena. "Protein expression in prostate cancer /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-617-4/.
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Gillaspy, Glenda E. "Expression of genes and differentiation markers in human glioblastoma cell lines." Case Western Reserve University School of Graduate Studies / OhioLINK, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=case1055265679.
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Moulin, Danielle S. "Regulation of expression of the CFTR gene." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298347.
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Gulyás, Miklós. "Mesothelial differentiation, mesothelioma and tumor markers in serous cavities /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-566-2/.
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Valdman, Alexander. "Molecular genetic markers of prostate cancer development /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-618-9/.
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Roupaka, Sofia. "Functional genomics approach to identifying peripheral markers for sheep scrapie." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/33306.
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Scrapie is a transmissible spongiform encephalopathy (TSE) of sheep and goats, for which there is currently no ante-mortem diagnostic test. A rapid, ante-mortem diagnostic test for scrapie would also potentially be important for other TSEs such as bovine spongiform encephalopathy (BSE) and variant Creutzfeldt Jakob's disease (vCJD). The hypothesis of this study was that there is differential gene expression in the blood and peripheral tissues of scrapie infected animals, and that a panel of differentially expressed genes could be identified and used as surrogate markers of infection. An expression screening approach, using real-time PCR and an EST microarray, was used to identify genes that were differentially expressed between SSBP/1 infected and mock-infected control sheep. The animals used in this study were New Zealand Cheviot sheep of three genotypes, the highly susceptible VRQ/VRQ (incubation time 193 ± 12 days), the intermediately susceptible VRQ/ARR (incubation time 325 ± 36 days) and the disease resistant ARR/ARR (no clinical signs of disease), experimentally infected with scrapie strain SSBP/1 and sacrificed at various time points post infection. No differentially expressed candidates were identified in blood. Other microarray experiments in our group had demonstrated evidence of differential expression in spleen fractions enriched for follicular dendritic cells (FDCs). These data were analysed and candidates were selected for quantitative real-time PCR validation, with a view to assessing the expression of validated candidates in blood as a more targeted approach to identifying markers of infection. The gene Early Growth Response 1 (EGR1) emerged as an interesting candidate as its expression was found to be significantly up-regulated in FDC-enriched spleen samples of VRQ/VRQ and ARR/ARR animals over a number of time points post infection. EGR1 expression was steady among all mock-infected controls. There was, however, no evidence of differential expression of EGR1 in blood. This is the first report of differential expression of EGR1 in preclinical spleen samples in sheep. EGR1 is an attractive candidate for a surrogate marker of preclinical infection, as its levels rise very early after infection and remain elevated for a sustained amount of time in the VRQ/VRQ sheep. Elevated expression is also detectable in VRQ/ARR and in ARR/ARR sheep. Further studies with larger sample numbers would be necessary to more accurately estimate the extent of differential expression and to assess its true worth as a diagnostic marker. Expression studies in samples from other TSEs and non-TSE neuropathological disease would also be necessary to establish whether differential expression of EGR1 is specific to TSE disease.
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Grover, Rajiv. "Oncogene expression in malignant melanoma : markers of prognosis and targets for gene therapy." Thesis, Queen Mary, University of London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266579.
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Burk, Janina, Claudia Gittel, Sandra Heller, Bastian Pfeiffer, Felicitas Paebst, Annette B. Ahrberg, and Walter Brehm. "Gene expression of tendon markers in mesenchymal stromal cells derived from different sources." Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-157823.
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Background: Multipotent mesenchymal stromal cells (MSC) can be recovered from a variety of tissues in the body. Yet, their functional properties were shown to vary depending on tissue origin. While MSC have emerged as a favoured cell type for tendon regenerative therapies, very little is known about the influence of the MSC source on
their properties relevant to tendon regeneration. The aim of this study was to assess and compare the expression of tendon extracellular matrix proteins and tendon differentiation markers in MSC derived from different sources as well as in native tendon tissue. MSC isolated from equine bone marrow, adipose tissue, umbilical cord tissue, umbilical cord blood and tendon tissue were characterized and then subjected to mRNA analysis by real-time polymerase chain reaction. Results: MSC derived from adipose tissue displayed the highest expression of collagen 1A2, collagen 3A1 and decorin compared to MSC from all other sources and native tendon tissue (p < 0.01). Tenascin-C and scleraxis
expressions were highest in MSC derived from cord blood compared to MSC derived from other sources, though both tenascin-C and scleraxis were expressed at significantly lower levels in all MSC compared to native tendon tissue (p < 0.01). Conclusions: These findings demonstrate that the MSC source impacts the cell properties relevant to tendon regeneration. Adipose derived MSC might be superior regarding their potential to positively influence tendon matrix reorganization.
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Peake, Simon Thomas Charles. "Aberrant expression of homing markers on dendritic cells drives inflammation in Crohn's disease." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/31866.
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CD is a chronic transmural inflammatory disease of the gut. The aetiology of CD is unknown, but is likely to result from dysregulated innate immune responses to gut microbiota leading to over activation of the acquired immune system in a genetically susceptible host. Inflammation occurs anywhere from mouth to anus, in addition to extra-intestinal sites. This compartmentalisation of the inflammatory process is linked to tissue-specific innate immune mechanisms and immune cell homing. DCs play a key role in discriminating between gut commensal microbiota and harmful pathogens, directing T-cell polarisation and directing immune cells to specific anatomical locations by expressing and imprinting homing markers. Improved understanding of the immunopathogenic basis of inflammation in CD has led to the development of more efficacious medical therapy, in particular, targeting the pro-inflammatory cytokine TNFα. The precise mechanism of action of TNFα blockade in CD remains unclear. We found homing marker expression on circulating DCs in patients with CD closely correlates with anatomical phenotype of inflammation. When immune cells are cultured with IFX we found homing marker expression on monocytes and T-cells changed from a gut-homing to skin-homing phenotype., perhaps explaining the phenomenon of 'paradoxical inflammation' seen in some patients treated with anti-TNFα therapy. Blood-enriched DCs isolated from patients with active CD had higher levels of pro-inflammatory cytokines in culture medium. IFX culture resulted in reduced concentrations of pro-inflammatory cytokines and decreased gut-homing marker expression. Finally, we examined the functional effects of IFX-pre-treated-LDCs on T-cells. There was a dose-dependent reduction in LDC stimulatory capacity with increasing concentrations of IFX, but no changes in T-cell phenotype. The effect of IFX on the immune system goes beyond TNFα blockade alone. This work has identified several mechanisms by which IFX interacts with immune cells in vitro, which may result in changes to CD inflammatory process in vivo.
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Ying, Jiawei [Verfasser], and Bruno [Akademischer Betreuer] Reichart. "Gene expression of inflammation markers in cardiac xenotransplantation / Jiawei Ying ; Betreuer: Bruno Reichart." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1218465646/34.
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Stoltzfus, Patricia. "Molecular markers reflecting malignant transformation and tumor progression /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-888-2.
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Nopp, Anna. "Characterisation of eosinophil activity markers : relation to allergic inflammation and apoptosis /." Stockholm : Karolinska Univ. Press, 2002. http://diss.kib.ki.se/2002/91-7349-129-2.
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Mathias, Daniel, Ronald E. J. Mitchel, Mirela Barclay, Heather Wyatt, Michelle Bugden, Nicholas D. Priest, Stewart C. Whitman, Markus Scholz, Manja Kamprad, and Annegret Glasow. "Low-dose irradiation affects expression of inflammatory markers in the heart of ApoE -/- mice." Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-169681.
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Epidemiological studies indicate long-term risks of ionizing radiation on the heart, even at moderate doses. In this study, we investigated the inflammatory, thrombotic and fibrotic late responses of the heart after low-dose irradiation (IR) with specific emphasize on the dose rate. Hypercholesterolemic ApoE-deficient mice were sacrificed 3 and 6 months after total body irradiation (TBI) with 0.025, 0.05, 0.1, 0.5 or 2 Gy at low (1 mGy/min) or high dose rate (150 mGy/min). The expression of inflammatory and thrombotic markers was quantified in frozen heart sections (CD31, E-selectin, thrombomodulin, ICAM-1, VCAM-1, collagen IV, Thy-1, and CD45) and in plasma samples (IL6, KC, MCP-1, TNFα, INFγ, IL-1β, TGFβ, INFγ, IL-10, sICAM-1, sE-selectin, sVCAM-1 and fibrinogen) by fluorescence analysis and ELISA. We found that even very low irradiation doses induced adaptive late responses, such as increases of capillary density and changes in collagen IV and Thy-1 levels indicating compensatory regulation. Slight decreases of ICAM-1 levels and reduction of Thy 1 expression at 0.025–0.5 Gy indicate anti-inflammatory effects, whereas at the highest dose (2 Gy) increased VCAM-1 levels on the endocardium may represent a switch to a pro-inflammatory response. Plasma samples partially confirmed this pattern, showing a decrease of proinflammatory markers (sVCAM, sICAM) at 0.025–2.0 Gy. In contrast, an enhancement of MCP-1, TNFα and fibrinogen at 0.05–2.0 Gy indicated a proinflammatory and prothrombotic systemic response. Multivariate analysis also revealed significant age-dependent increases (KC, MCP-1, fibrinogen) and decreases (sICAM, sVCAM, sE-selectin) of plasma markers. This paper represents local and systemic effects of low-dose irradiation, including
also age- and dose rate-dependent responses in the ApoE-/- mouse model. These insights in the multiple inflammatory/thrombotic effects caused by low-dose irradiation might facilitate an individual evaluation and intervention of radiation related, long-term side effects but also give important implications for low dose anti-inflammatory radiotherapy.
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Jardim, Juscelino de Freitas 1989. "Clinicopathological analysis and expression of proliferation markers in advanced stage oral squamous cell carcinoma." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288145.
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Orientador: Luiz Paulo KowalskiTaxto em português e inglês
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
Made available in DSpace on 2018-08-24T18:08:30Z (GMT). No. of bitstreams: 1 Jardim_JuscelinodeFreitas_M.pdf: 8723200 bytes, checksum: c5a9b07e52853342905f7f5f7df0ed12 (MD5) Previous issue date: 2014
Resumo: O carcinoma de células escamosas (CEC) é a neoplasia maligna mais frequente na cavidade bucal, correspondendo a quase 95% destas lesões, e cerca de 38% dos tumores malignos de cabeça e pescoço. Mais de 50% dos portadores deste tipo de tumor apresentam estágio avançado da doença no momento do diagnóstico, fator que reflete em baixas taxas de sobrevidas em 5 anos. Fatores histopatológicos como invasões perineural e vascular têm sido relacionadas com recorrência e baixas taxas de sobrevida. Ainda, pacientes com mesmo sítio de acometimento e histologia tumorais semelhantes podem ter comportamentos biológicos distintos, frente a isso, a importância da busca por biomarcadores para predizer prognóstico e risco estratificado. O propósito deste estudo consistiu em avaliar o significado clínico e prognóstico dos fenômenos de invasão perineural (IP) e invasão vascular (IV) bem como da imunoexpressão de Mcm-2, Ciclina D1, Ki-67 e p53 em CECs de língua e assoalho em estádio clínico avançado. Foi realizado um levantamento retrospectivo de pacientes com CEC de língua e assoalho de boca em estádio clínico avançado, tratados previamente por cirurgia no departamento de cirurgia de cabeça e pescoço do AC Camargo Cancer Center entre os anos de 1998 e 2009. De 142 casos elegíveis para o estudo, 88 blocos de parafina foram resgatados do departamento de Patologia da mesma instituição e reações de imunoístoquímica foram realizadas para os marcadores já descritos anteriormente. Todas as lâminas passaram por um processo de digitalização através do equipamento Aperio System (Vista, CA, USA). Quantificações das marcações foram obtidas através do software Imagescope (Aperio System, USA) e testes estatísticos com nível de significância de 5% foram tomados para acessar correlações com prognóstico. Os resultados mostraram que tanto IP (p< 0,001) como IV (p= 0,01) influenciaram negativamente a sobrevida em 5 anos dos pacientes. Outros fatores como tamanho tumoral (estádio T) (p=0,003), estádio N+ (p= 0,002) e ruptura de cápsula linfonodal (p< 0,001) também obtiveram impacto em predizer sobrevida. Com relação aos marcadores de proliferação celular, altas taxas de Mcm-2 (p<0,001) e Ciclina D1 (p = 0,005) tiveram relação direta com taxas de sobrevida global menores que 5 anos, enquanto p53 e Ki-67 não alcançaram significância. Mcm-2 também foi altamente relacionado com recorrência (p=0,025), enquanto Ciclina D1 e p53 foram correlacionados com estádio N. Em conclusão, o aumento na expressão de Mcm-2 e Ciclina D1 exibem importante correlação com prognóstico e sobrevida dos pacientes, assim como fatores histopatológicos como invasões perineural
Abstract: Oral squamous cell carcinoma (OSCC) is the most common malignancy in the oral cavity, accounting for almost 95% of these injuries, and about 38% of malignant tumors of the head and neck. More than 50% of all patients have advanced disease at the time of diagnosis, factor that reflects in low survival rates at 5 years. Histopathological factors such as vascular and perineural invasion have been associated with low rates of recurrence and survival. Moreover, patients with the same site and similar histology may have different biological behaviors, due to their differing biological characteristics and therefore exist an interest in the identification of biomarkers that could be used in the clinical practice in order to better prognosticate and risk-stratify patients. The aim of this study was to evaluate the prognostic significance of the perineural invasion (PNI) and lymphovascular invasion (LVI) as well as the expression of Mcm-2, Cyclin D1, Ki-67 and p53 in advanced stage OSCC. A retrospective review of patients with OSCC of the tongue and floor of mouth in advanced clinical stage, treated by surgery in the Department of head and neck of the AC Camargo Cancer Center between the years 1998 and 2009 was conducted. Of 142 eligible cases, 88 paraffin-embedded tissue were rescued from the Department of Pathology of the same institution and immunohistochemistry reactions were performed for markers previously described. All slides have gone digitalized through the equipment Aperio System (Vista, CA, USA). Quantifications were performed from Imagescope software (Aperio System, USA) and statistical tests with significance level of 5% were taken to access correlations with prognosis. Our results showed that both PNI (p<0.001) as LVI (p=0.01) had negatively influence on overall survival of the patients. Other factors as T stage (p=0.003), positive lymph node (p=0.002) and extracapsular nodal spread (p<0.001) also had prognostic impact to predict poor survival. In relation to the proliferative markers, we found that high expression of Mcm-2 (p<0.001) and Cyclin D1 (p=0.005) had strong association with low rates of overall survival, whereas p53 and Ki-67 did not reach significance with this parameter. Mcm-2 was also correlated with recurrence (p=0.025). Cyclin D1 and p53 were significance with the N stage. In conclusion, the increasing expression of Mcm-2 and Cyclin D1 showed important correlation with prognosis and survival as well as histopathological features, such as PNI
Mestrado
Estomatologia
Mestre em Estomatopatologia
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Kenny, Emma. "Peripheral CD4'+ T cell subsets involved in primary and secondary immune responses." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343045.
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Hooi, Wei Yeng. "Search for early molecular markers of the mantled floral variation of oil palm." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTS244.
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Titre du projet: Recherche de marqueurs moléculaires précoces de l’anomalie florale mantled du palmier à huile Objectifs : - identifier des marqueurs d’expression de la variation somaclonale mantled par comparaison entre les transcriptomes conformes et variants.- valider la capacité de discrimination des marqueurs sélectionnés lors des stades précoces du processus in vitro. Stratégie et Méthode: Analyse transcriptomique de l’inflorescence normale de palmier à huile et construction d’un transcriptome de référence. Technique : RNAseq, séquençage Illumina.Identification des séquences et voies de régulation d’intérêt. Technique: analyse bioinformatique des données de séquençage.Comparaison entre les trancriptomes issus d’inflorescences normales vs. mantled par re-séquençage de banques obtenues ) partir de différents génotypes clonaux. Technique : Illumina.Identification des séquences présentant de manière cohérente des profils d’expression dépendant du phénotype. Technique : analyse bioinformatique des données de séquençage, analyse statistique des profils d’expression. Validation des marqueurs candidats sur des paires de régénérants normal/mantled issus de lignées clonales variées, ainsi que sur des cultures in vitro à différents stades du processus de régénération. Technique : PCR quantitative (q-PCR)Project title : Search for early molecular markers of the mantled floral variation of oil palmObjectives : - identifying expression markers of the mantled somaclonal variation through the comparison between the true-to-type and the variant transcriptome. - assessing the discriminating power of the selected markers at early stages of the in vitro process.Strategy and Methods : Transcriptomic analysis of the normal oil palm inflorescence, construction of a reference transcriptome. Technique : RNAseq, Illumina sequencing.Identification of sequences and pathways of interest. Technique : bioinformatic analysis of sequencing data.Comparison between the normal and the mantled inflorescence transcriptome through the re-sequencing of libraries generated from several different clonal lines. Technique : Illumina. Identification of sequences displaying consistently a phenotype-dependent differential expression pattern. Technique : bioinformatic analysis of sequencing data, statistical analysis of expression patterns. Validation of candidate markers on normal/mantled regenerant palm pairs from different clonal lines and on normal-/mantled-derived in vitro cultures at various stages of the industrial regeneration process. Technique : quantitative PCR (q-PCR)
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Leung, Cheuk-man, and 梁卓文. "A study of BARX2 expression in esophageal squamous cell carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B47560460.
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Background
Esophageal carcinoma mainly affects middle aged to elderly males. It ranks the
ninth most common cancer world-wide. The main histological types are squamous
cell carcinoma and adenocarcinoma. In Hong Kong, esophagus squamous cell
carcinoma (ESCC) is by far the more common. BARX2 is a human homeobox gene
located at 11q24-q25, encoding a protein of 254 amino acids. Recent researches show
that its expression in breast cancer promotes cellular invasion.
Objectives
The study aimed to test the hypothesis that BARX2 is a prognostic marker in
ESCC. BARX2 expression in ESCC was correlated with patient survival and other
clinicopathologic parameters in a cohort of patients.
Material and Methods
Records of ESCC patients were obtained retrospectively from the computerized
database of Queen Mary Hospital. ESCC patients, who underwent esophagectomy in
the hospital from 1998 to 2005 but without receiving prior chemotherapy or
radiotherapy directed to the tumor, were selected. Tumor staging was done according
to the 6th edition of AJCC Cancer Staging Manual. Immunohistochemical staining
for BARX2 expression was performed on paraffin sections of the primary ESCC
tissues sampled in a tissue microarray constructed for research purposes. The pattern
of BARX2 expression in nucleus and cell cytoplasm of tumor cells was recorded and
the staining intensity scored on a 4-point scale. The scores were statistically analyzed
together with the various clinicopathologic parameters. BARX2 expression and
patient survival time were analyzed by the log-rank test.
Results
A total of 78 ESCC patients were recruited. At the time of data analysis, 52
(66.7%) patients were dead. The overall median survival of patients was 14.3 months.
BARX2 was found to be mainly expressed in the cytoplasm of tumor cells while
non-tumor epithelium showed strong nuclear expression. Patients with high level
BARX2 expression had short survival time, though the difference did not reach
statistical significance (p=0.075). Within the subgroup of lower T-stage ESCC (T1-3),
high level BARX2 expression was significantly associated with shorter survival time
(p=0.042). However, differential BARX2 expression did not affect survival time
within the group of patients who had advanced stage (T4) disease (p=0.525). In
patients who had no regional lymph node metastasis (N0), high level BARX2
expression was associated with shorter survival time (p=0.023). However, when
patients had regional lymph node metastases (N1), BARX2 expression did not affect
patient survival time (p=0.533). Patients whose ESCC showed moderate
differentiation in a three-tier tumor grading system, when accompanied with low level
BARX2 expression, had longer survival time (p=0.029). However, BARX2
expression did not affect survival time when ESCC showed either well differentiation
(p=0.462) or poor differentiation (p=0.637). Multivariate analysis showed patient age
and T-stage to be the only two independent parameters of prognostic significance
(p=0.025 and p=0.036 respectively).
Conclusions
BARX2 expression in ESCC was aberrant and mainly cytoplasmic. It was
inversely correlated with patient survival time in early ESCC disease (T1-T3 or N0).
BARX2 expression evaluated by immunohistochemistry could be a useful and
practical prognostic marker of ESCC in its early stages, when the proper decision on
treatment would be critical for the patients.published_or_final_version
Pathology
Master
Master of Medical Sciences
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ISHIGURO, NAOKI, HIROHITO MITSUYAMA, YOHEI ONO, MOTOSHIGE NAKASHIMA, HIDEKI HIRAIWA, TADAHIRO SAKAI, and TAKASHI HAMADA. "Surface Markers and Gene Expression to Characterize the Differentiation of Monolayer Expanded Human Articular Chondrocytes." Nagoya University School of Medicine, 2013. http://hdl.handle.net/2237/17606.
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Bourgeois, Marie Meagher. "Gender and Cocaine Use Influence the Expression of Urinary Markers of Inflammation and Oxidative Stress." Scholar Commons, 2010. http://scholarcommons.usf.edu/etd/3572.
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The purpose of this study was to investigate whether or not gender differences may be present in the expression of a number of urinary proteins which may serve as markers of inflammation and oxidative stress. Males and females have different patterns of illness and different life spans, suggesting basic biological traits exert significant control on the incidence of rhabdomyolysis, renal failure, atherosclerosis, myocardial ischemia, myocardial contraction band formation, autoimmune disorders and general inflammatory diseases. Men are at greater risk for cardiovascular disease; however women, particularly elderly women, have higher fatality rates due to heart failure. Renal diseases progress far more quickly in men, possibly due to testosterone. Men also have higher kidney bulk related to androgen expression. Gender disparity may be most obvious in autoimmune disorders; of the estimated 8.5 million people diagnosed with autoimmune disorders, approximately 80% are women. Hashimoto’s thyroiditis, the most common form of hypothyroidism, is up to 10 times more common in women. Systemic Lupus Erythematosus (SLE), an autoimmune disease characterized by acute and chronic inflammation, is 9 times more common in women. Rheumatoid arthritis (RA), an autoimmune disease affecting approximately 1.3 million people in the United States, is four times more common in women. Diabetes mellitus (DM), affecting more than 17 million people – the majority of which are women, is linked to microvascular and macrovascular diseases such as kidney failure, strokes and atherosclerosis. These conditions are linked to physiological changes that may alter the expression of certain biomarkers of inflammation and oxidative stress.
Over the past several decades, it has become increasingly clear that the role of diet, smoking, and other lifestyle choices clearly influence the etiology and pathophysiology of these diseases. The use of drugs, both licit and illicit, has been clearly linked to many of these diseases. Illicit substances, particularly cocaine, have been demonstrated to produce pathophysiological changes to many systems in the body which can greatly influence the progression of existing and drug-induced disease states leading to systemic damage. A relationship between the expression of markers of inflammation, oxidative stress, cardiac damage, or other systemic injury, gender and cocaine use has not been clearly established.
Urine is an important medium for assessment of general health status. It has classically been used to monitor disease states; glucosuria as an indicator of diabetes and renal dysfunction, microorganisms signifying urinary tract or bladder infection, and biomarkers such as human chorionic gonadotropin to confirm pregnancy. Recently urine has been used to assess biomarker expression and disease states. Urine is an ideal clinical tool for toxicological screens; it is readily accessible, non invasive and typically supplied in sufficient quantity to accommodate multiple tests. In this study, urine specimens were collected and analyzed for creatinine, cocaine, total protein, aldosterone, c-reactive protein (hsCRP), myeloperoxidase (MPO), microalbumin (MAB), neutrophil gelatinase-associated lipocalin (NGAL), heat shock protein 90α (hsp90α), vascular endothelial growth factor (VEGF), myoglobin, pro atrial natriuretic peptide (proANP) and interleukins 1α, 1 β , and 6 using ELISA and colorimetric assays.
Urine specimens that tested negative for all illicit substances in the standard National Institute on Drug Abuse (NIDA) 10 panel showed differences in a number of these biomarkers which strongly suggested significant differences between males and females for aldosterone, IL1α and IL1β. In addition, significance is suggested for MPO and CRP. Although sex specific differences in serum expression have been noted for some of the markers in both animal and human models, this has not been previously demonstrated in human urine. This may have implications for what is typically referred to as ‘normal’ values. Gender specific differences were not apparent in urine specimens that tested positive for cocaine. Also, in males only, the levels of myoglobin and aldosterone significantly increased.
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Dang, Chi Vu Luan. "Identification of predictive markers of immunosenescence, particularly, the study of BACH2 and PRDM1 gene expression." Doctoral thesis, Universite Libre de Bruxelles, 2018. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/271524.
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BACKGROUND Aging is characterized by a progressive decline in immune surveillance that favors tumor development in older patients. One of the mechanisms used by malignant cells to escape immune surveillance is genetic or epigenetic modifications of tumor suppressor genes. Studies in B-cells and our previous report on the correlation between 6q deletion and progression into a T cell lymphoproliferative disease, identifying the BACH2 gene as a candidate tumor suppressor gene. Together, BACH2 and PRDM1 are described as having a fundamental role in oncogenesis, differentiation and apoptosis control of B and T lymphocytes during oxidative stress. Furthermore, several studies in mice model suggested that BACH2 gene is sensitive to DNA damage during aging and plays a role in the cellular senescence process. The impact of these genes in the immune response of the older adult is unclear. OUR HYPOTHESIS 1. Recent reports (including our previous study) on the transcription factor BACH2 and PRDM1 have highlighted their impact on immunological changes. It has been shown that BACH2 is highly sensitive to transcription-blocking DNA lesions in aged mice. Despite the growing interest in BACH's role, there have been many studies in mice models, studies on BACH2 in humans are still limited. This concept prompted us to investigate the variation of BACH2 and PRDM1 expression with age in major lymphocyte subsets from healthy individuals. 2. Apoptosis and senescence are two types of cellular response affected by cancer and aging processes, albeit through different mechanisms. Carcinogenesis is associated with a progressive reduction in the ability of the cells to trigger apoptosis and senescence. The lymphocytes apoptosis process and the markers of cell senescence were thus studied in both populations. 3. Chronic lymphocytic leukemia, one of the aging-related diseases, is characterized by the accumulation of “anergic” phenotypes in both B-cells and T-cells. In chronic lymphocytic leukemia, malignant cell anergy is associated with failure of inducing PRDM1 (BLIMP1), a critical regulator of differentiation into plasma cells, and that epigenetic modification account for such failure. We thus examined the expression of specific transcription factors BACH2 and PRDM1 in the leukemic lymphocytes subsets and compared the results with age-matched normal population. POPULATION & METHODS Blood samples were obtained from 60 healthy donors, aged from 20 to 90 years, and 41 untreated chronic lymphocytic leukemia were studied. Lymphocyte subsets (CD19+ B-cells, CD8 T-cells, CD4 T-cells, CD4 naïve T-cells, CD4 effector memory T-cells) were isolated for subsequent molecular analyses using the MACS Technology (Miltenyi), with the purity of each lymphocyte subpopulation between 95%-99%. BACH2, PRDM1, IL-4, IFNG, TP53, CDKN2A (p16INK4A), PDCD1 (PD-1) and CD274 (PD-L1) mRNA transcripts were quantified using qRT-PCR. BACH2 protein expression was examined by Western blotting. To investigate BACH2-target genes in apoptosis, we performed a “Human Apoptosis EpiTect ChIP qPCR Array” profiles including 84 key genes involved in programmed cell death. Etoposide was used to induce intracellular oxidative stress followed by cell apoptosis. Apoptotic cells were identified with the annexin-V-FITC apoptosis detection kit (BD Pharmingen). To measure ß-galactosidase by flow cytometry, we used Fluorescein-di-beta-D-galactopyranoside as a substrate for beta-galactosidase (Molecular Probes).RESULTS 1. BACH2 and PRDM1 gene expression were strongly correlated with age in healthy donor’s major lymphocyte subsets. BACH2 mRNA expression declined by age, with statistically significant differences observed in all lymphocyte subsets: CD4+, CD4+ naïve, CD4+ memory, CD8+ T-cells and CD19+ B-cells (p<0.0001, <0.0001, 0.0118, <0.0001 and 0.0004 respectively). In contrast, PRDM1 gene expression significantly increased with age in the same subpopulations. The phenotypic changes of immune lymphocytes are related to the BACH2 and PRDM1 gene expression. Along with the decline of BACH2, the older group had a severe decrease in number and quality of cytotoxic T-cells (p=0.0005 and <0.0001), while increasing the rate exhausted T-cells that highly expressed of PD-1 and PD-L1. Both PCCD1 (PD-1) and CD274 (PD-L1) gene expression had inversely correlated with BACH2 in the same lymphocyte subsets (p=0.0342; 0.0254 and 0.0429 respectively). Western blotting analysis demonstrated that BACH2 protein expressions in the T and B cell subpopulations significantly correlated with transcript expression. 2. Age-related BACH2 down-regulation enhanced the increasing of senescent cells and the resistance to apoptosis in the major lymphocyte subsets. We, further, found the correlation of BACH2 with senescence markers, such as p16INK4A (CDKN2A) and SA-β-GAL along with loss of CD28+ on T-lymphocytes. ChIP-qPCR Array demonstrated that BACH2 bound directly several genes involved in programmed cell death. A reduction in apoptosis was observed with age in CD4+ T-cells and CD19+ B-cells (p=0.03 in both subpopulations). As recently reported for BACH2-deficient mice, our data show that BACH2 down-regulation is strongly correlated with a decrease in CD4+ T-cell and CD19+ B-cell apoptosis (r=0.57 and 0.61). 3. Decreases in BACH2 mRNA expression were greater in CD4+ and CD8+ T-cells, as well as leukemic B-cell subpopulations from untreated CLL patients, compared with age-matched healthy donors (p=0.0006; 0.0003 and 0.0083, respectively). As expected, PRDM1 was significantly upregulated in the CD4+ and CD8+ T-cell subpopulations (p=0.003 and 0.001, respectively) from CLL patients but not their leukemic B-cells. CONCLUSION In this research work, we examined BACH2 and PRDM1 gene expression to investigate its potential as a predictive marker of aging. Our data suggest BACH2 and PRDM1 mRNA expression, in the inverse correlation, associated with the phenotypic changes of immune lymphocytes in aging. Age-related BACH2 down-regulation enhanced the increasing of exhausted phenotypes, senescent cells and resistance to cell apoptosis. BACH2 and PRDM1 could involve in cellular and immunological functions deterioration of the immunosenescence process. Further investigations on BACH2 and PRDM1 genetic mutations provide a better understanding of the role of the unbalanced expression of those genes in lymphocytes functions and survival according to age.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
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Li, Ronggai. "Characterisation of cell markers, cytokines and transcription factors involved in B cell responses from cartilaginous fish." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=20771.
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Cartilaginous fish are the most ancient lineage to possess an adaptive immune system however nothing is known about the processes involved in the development, maintenance or proliferation of B cells in this group. In this thesis studies were undertaken to explore whether transcription factors, cytokines and cell surface markers that are involved in B cell immune responses in mammals are also present in cartilaginous fish. Through sequence database mining forty-one genes involved in B cell immune biology were found; of these twelve were B cell transcription factors. The presence of important B cell transcription factors, such as EBF1, pax5, E2A, Blimp1, PU.1 and Bcl6 suggests that B cells in cartilaginous fish probably undergo a similar developmental pathway as those in mammals. Eight cytokines, eleven cytokine receptors and four B cell surface markers were also identified, including CD40L, BAFF and CD79α that were further studied in this thesis. I cloned CD40L and BAFF from cartilaginous fish, both members of the tumour necrosis factor family and found cartilaginous fish BAFF genes have an extra exon that forms a unique α-helix insertion, and which may impact on receptor binding. The importance of all three molecules for the adaptive immune response was indicated by relatively high expression in shark immune tissue, such as spleen, gut-associated lymphoid tissue, gill and the Leydig organ, and the fact that their expression could be induced by immunostimulants, such as pokeweed mitogen. The finding that CD79α expression significantly correlates with those of immunoglobulin heavy-chains and the co-expression of CD79α and IgM on the B cell surface indicate that as in mammals CD79α in cartilaginous fish is expressed by B cells and associates with surface-bound immunoglobulin to form the active B cell receptor. Thus CD79α may serve as a pan B cell marker in future immunological studies in cartilaginous fish.
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Petty, Aaron. "Novel MIG-7 expression increases tumor cell invasion and tumor progression." Online access for everyone, 2008. http://www.dissertations.wsu.edu/Thesis/Spring2008/a_petty_040908.pdf.
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Swagell, Christopher Dean. "Molecular markers of obesity and diabetes." Thesis, Queensland University of Technology, 2007. https://eprints.qut.edu.au/35762/1/Christopher_Swagell_Thesis.pdf.
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Recently it has been shown that the consumption of a diet high in saturated fat is associated with impaired insulin sensitivity and increased incidence of type 2 diabetes. In contrast, diets that are high in monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs), especially very long chain n-3 fatty acids (FAs), are protective against disease. However, the molecular mechanisms by which saturated FAs induce the insulin resistance and hyperglycaemia associated with metabolic syndrome and type 2 diabetes are not clearly defined.
It is possible that saturated FAs may act through alternative mechanisms compared to MUFA and PUFA to regulate of hepatic gene expression and metabolism. It is proposed that, like MUFA and PUFA, saturated FAs regulate the transcription of target genes. To test this hypothesis, hepatic gene expression analysis was undertaken in a human hepatoma cell line, Huh-7, after exposure to the saturated FA, palmitate. These experiments showed that palmitate is an effective regulator of gene expression for a wide variety of genes. A total of 162 genes were differentially expressed in response to palmitate. These changes not only affected the expression of genes related to nutrient transport and metabolism, they also extend to other cellular functions including, cytoskeletal architecture, cell growth, protein synthesis and oxidative stress response. In addition, this thesis has shown that palmitate exposure altered the expression patterns of several genes that have previously been identified in the literature as markers of risk of disease development, including CVD, hypertension, obesity and type 2 diabetes. The altered gene expression patterns associated with an increased risk of disease include apolipoprotein-B100 (apo-B100), apo-CIII, plasminogen activator inhibitor 1, insulin-like growth factor-I and insulin-like growth factor binding protein 3. This thesis reports the first observation that palmitate directly signals in cultured human hepatocytes to regulate expression of genes involved in energy metabolism as well as other important genes.
Prolonged exposure to long-chain saturated FAs reduces glucose phosphorylation and glycogen synthesis in the liver. Decreased glucose metabolism leads to elevated rates of lipolysis, resulting in increased release of free FAs. Free FAs have a negative effect on insulin action on the liver, which in turn results in increased gluconeogenesis and systemic dyslipidaemia. It has been postulated that disruption of glucose transport and insulin secretion by prolonged excessive FA availability might be a non-genetic factor that has contributed to the staggering rise in prevalence of type 2 diabetes. As glucokinase (GK) is a key regulatory enzyme of hepatic glucose metabolism, changes in its activity may alter flux through the glycolytic and de novo lipogenic pathways and result in hyperglycaemia and ultimately insulin resistance. This thesis investigated the effects of saturated FA on the promoter activity of the glycolytic enzyme, GK, and various transcription factors that may influence the regulation of GK gene expression. These experiments have shown that the saturated FA, palmitate, is capable of decreasing GK promoter activity. In addition, quantitative real-time PCR has shown that palmitate incubation may also regulate GK gene expression through a known FA sensitive transcription factor, sterol regulatory element binding protein-1c (SREBP-1c), which upregulates GK transcription.
To parallel the investigations into the mechanisms of FA molecular signalling, further studies of the effect of FAs on metabolic pathway flux were performed. Although certain FAs reduce SREBP-1c transcription in vitro, it is unclear whether this will result in decreased GK activity in vivo where positive effectors of SREBP-1c such as insulin are also present. Under these conditions, it is uncertain if the inhibitory effects of FAs would be overcome by insulin. The effects of a combination of FAs, insulin and glucose on glucose phosphorylation and metabolism in cultured primary rat hepatocytes at concentrations that mimic those in the portal circulation after a meal was examined. It was found that total GK activity was unaffected by an increased concentration of insulin, but palmitate and eicosapentaenoic acid significantly lowered total GK activity in the presence of insulin. Despite the fact that total GK enzyme activity was reduced in response to FA incubation, GK enzyme translocation from the inactive, nuclear bound, to active, cytoplasmic state was unaffected. Interestingly, none of the FAs tested inhibited glucose phosphorylation or the rate of glycolysis when insulin is present. These results suggest that in the presence of insulin the levels of the active, unbound cytoplasmic GK are sufficient to buffer a slight decrease in GK enzyme activity and decreased promoter activity caused by FA exposure. Although a high fat diet has been associated with impaired hepatic glucose metabolism, there is no evidence from this thesis that FAs themselves directly modulate flux through the glycolytic pathway in isolated primary hepatocytes when insulin is also present.
Therefore, although FA affected expression of a wide range of genes, including GK, this did not affect glycolytic flux in the presence of insulin. However, it may be possible that a saturated FA-induced decrease in GK enzyme activity when combined with the onset of insulin resistance may promote the dys-regulation of glucose homeostasis and the subsequent development of hyperglycaemia, metabolic syndrome and type 2 diabetes.
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Trufant, Joshua William. "Phactr1 as a novel biomarker to distinguish malignant melanoma from nevus." Yale University, 2010. http://ymtdl.med.yale.edu/theses/available/etd-04222010-200934/.
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An experienced dermatopathologist can reliably diagnose most cutaneous malignant melanomas based on well-established morphologic characteristics. However, in a minority of cases, traditional histopathologic evaluation and immunohistochemistry (IHC) are inadequate to confidently distinguish melanoma from benign melanocytic lesions such as Spitz nevi and dysplastic nevi. The advent of high-throughput gene expression array technology has resulted in the identification of hundreds of potential molecular diagnostic biomarkers, but no single chromosomal, DNA, RNA or protein marker has yet been shown to differentiate melanoma from nevus with sensitivity and specificity approaching 100%. We selected the protein products of 11 genesATP1B1, CYCLIN D1, DLX-1, HOXB13, LIF, MEIS2, MITF, MYC, PHACTR1, PTPRF and TWISTup-regulated in melanoma cell-culture and tissue-based expression arrays as candidate diagnostic biomarkers for preliminary investigation. Based on the results of our pilot studies, we proposed that increased expression of Phactr1 protein, as measured by IHC, could be used to differentiate malignant melanomas from nevi. We applied Phactr1 monoclonal antibody to a 480-core tissue microarray that included samples from 28 nevi and 62 primary melanomas. A simple scoring algorithm derived from this data distinguished primary melanoma from nevus in the training set with 92% sensitivity and 100% specificity. These data suggest that Phactr1 immunohistochemical staining is a potentially useful aid in the clinical diagnosis of primary cutaneous melanoma.
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Homer, Elizabeth Gene. "Differentiation of neuroblastoma cell line B104 and characterisation of its ability to support HSV-1 replication." Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260844.
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Sousa, Joana. "Study of broodstock conditioning and determination of markers of gamete quality in the european clam Ruditapes decussatus." Thesis, Brest, 2014. http://www.theses.fr/2014BRES0034/document.
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La palourde grise européenne, Ruditapes decussatus est un coquillage d’importance socio-économique en Europe du Sud. Sa production est basée sur le recrutement naturel, qui est sujet à de fortes fluctuations annuelles. Au Portugal, les principales zones de production de cette espèce sont les lagunes de Ria de Aveiro et Ria Formosa. Ces populations présentent des réponses différentes à l'induction de la ponte, résultat d’intérêt dans un contexte d'amélioration de la production aquacole. L'objectif de cette thèse était d'améliorer les connaissances sur la reproduction de R. decussatus en utilisant des approches génomiques et cellulaires avec pour principales applications : le conditionnement de géniteurs et la qualité des gamètes.Le cycle de reproduction de ces populations a été caractérisé par histologie pour le développement gonadique, l’aire gonadique et le diamètre de l’ovocyte. À l'exception de la dynamique de la gamétogénèse, aucune différence significative n’a été identifiée entre populations. Grâce à un effort de séquençage (Illumina) de banque d’ADNc de différents tissus/stades pour enrichir en transcrits liés à la reproduction, une puce à ADN (oligoarray) représentant 51 678 contigs a été produite et utilisée afin de caractériser les bases transcriptomiques de la reproduction de R. decussatus. Des gènes différentiellement exprimés et la voie “N-Glycan biosynthesis”, impliquées dans l'interaction spermatozoïde – ovocyte, ont été soulignés, ce qui suggère que la reconnaissance entre gamètes puisse expliquer en partie les différences de succès d'induction de ponte entre ces populations. De plus, le transcriptome d’ovocytes collectés chez 15 femelles a été analysé par puce à ADN avec pour objectif d'identifier des potentiels marqueurs de la qualité des ovocytes. Des gènes codant pour des protéines chaperonnes, dont certains caractérisés comme des ARNm maternels essentiels pour le développement précoce, sont apparus différentiellement exprimés entre ovocytes de bonne et mauvaise qualité établie sur le taux de larves D obtenu. La présente étude fournit de nouvelles informations génomiques précieuses pour la compréhension de la reproduction de cette espèce et liste des gènes candidats codant la protéine disulforide isomerase (PDI), des calmodulines et la caspase 8 comme points de départ possibles pour des études fonctionnelles. Leur implication dans les phases importantes de la reproduction comme l’interaction spermatozoïde-ovocyte, la protection de l'ovocyte, la régulation du calcium et l'apoptose ont font des marqueurs potentiels de la qualité ovocytaire de cette espèceThe European clam, Ruditapes decussatus is considered a high value seafood product in Southern Europe. Its production is almost based on natural recruitment, which is subject to annual fluctuations. In Portugal, two of the main production areas of this species are Ria de Aveiro and Ria Formosa Lagoons. These populations were characterized by different responses to spawning induction, which is of great interest in a context of improvement of aquaculture. The purpose of this thesis was to improve the cellular and genomic knowledge on the reproduction of R. decussatus with major applications: broodstock conditioning and gamete quality.The reproductive cycle of the two populations was histologically characterized by comparing the gonadal development, gonadal area and oocyte diameter. With the exception of the dynamics of gonadal development, which may originate in the environment, no differences concerning gametogenesis were found. cDNA libraries of oocytes, larvae and gonads were sequenced on Illumina platform, to enrich resources in reproductive Expressed Sequence Tags, and a custom oligoarray representing 51,678 assembled contigs was then designed. To characterize the transcriptomic bases of reproduction, microarray analyses were performed in four gonadal maturation stages of the two populations. Differentially expressed probes and the “N-Glycan biosynthesis” pathway, potentially involved in sperm-egg interaction, were identified, suggesting that gamete recognition can explain part of the differences in terms of spawning induction success between populations.Moreover, microarray analyses were also performed in oocytes, with the objective of identifying potential markers of oocyte quality in this species. Genes coding for chaperone proteins demonstrated to be important markers of oocyte quality, with some of them being maternal mRNAs essential for early development.The present study provides new highly valuable genomic information for the understanding of reproduction of R. decussatus and emphasizes some candidate genes like protein disulforide isomerase (PDI), Calmodulin family and caspase 8 as possible starting points for further functional studies
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Grönberg, Malin. "Expression of Neuroendocrine Markers in Normal and Neoplastic Tissue with an Emphasis on Ghrelin and Obestatin." Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-130972.
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The aim of this thesis was to characterize the expression of the peptides ghrelin and obestatin, as well as other neuroendocrine markers in human normal tissues, in invasive breast cancer and a wide panel of neuroendocrine tumors (NETs). In normal tissues the expression of ghrelin and obestatin was mainly localized to the gastric mucosa, and in lesser extent in the remaining gastrointestinal tract, endocrine pancreas and mammary glands. Double immunofluorescence studies demonstrated that ghrelin and obestatin were co-localized in the same cells displaying the same cytoplasmic distribution. In normal breast tissue, ghrelin, obestatin, adrenomedullin, apelin and vesicular monoamine transporter 2 were specifically demonstrated in the luminal epithelial cells. Consecutive sections indicated that mammary epithelial cells could express several of these peptides. Secretogranin II and III were also detected in breast tissue, but their presence was restricted to the outer layer of myoepithelial cells, whereas chromogranin B immunoreactivity was found in both the epithelial and myoepithelial cells. Ghrelin and obestatin immunoreactivity was seen in invasive breast cancer, where the expression could be correlated to factors associated with prognosis. Furthermore, multivariate analysis indicated that ghrelin expression was a possible independent prognostic factor for prolonged recurrence-free and breast cancer-specific survival. In a panel of NETs and endocrine-related disorders it was revealed that ghrelin and obestatin immunoreactivity was primarily found in tumors originating from the respective normal tissues. The two proteins were detected in only a few cases and only occasional tumor cells were immunoreactive. In conclusion, ghrelin and obestatin are localized in the gastrointestinal tract, endocrine pancreas and mammary glands. This thesis has contributed to our understanding of the distribution of ghrelin and obestatin in both normal tissue and tumor cells. A potential role of ghrelin as a prognostic factor in invasive breast cancer has been identified and should be further explored.
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Montenegro, Raquel Carvalho. "Preliminar study of the expression of molecular markers in patients with stomach cancer, in Ceara State." Universidade Federal do CearÃ, 2003. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=12.
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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorIn search for a better understanding of the biology of tumors, molecular markers related to proliferation, resistance and apoptosis have been intensively studied in the different types of cancer. These markers can help on the elucidation of more specific therapeutic targets for the treatment of various tumors. It was observed that stomach cancer is the second most frequent cause of death in the world. In Brazil, this tumor is among the five major causes of death by cancer and the adenocarcinomas are held responsible for about 95% of all cases. For that matter, the expression of KI-67, PCNA, p53, bcl-2 and c-myc were evaluated independently and in a combined form in stomach adenocarcinomas. Thus, KI-67 and PCNA were confronted in order to determine which one would pose as a better cellular proliferation marker. Finally, a DNA extraction tecnique using CTAB was implemented on tumor tissue as well as the molecular analysis of the p53 gene by SSCP. The positive results were compared with those obtained by the imonohistochemistry analysis. The tumors were collected in surgical procedure, processed and classified histopathologically. The markers were detected by the imunohistochemical method SABP. The DNA was extracted by the CTAB method and the exons 5, 7 and 8/9 of the p53 gene analyzed by SABP. Some of the samples were obtained from biopsy arquives. The age range of the patients was between 61 and 70 years, with 48,1% of the tumors presenting an intestinal origin, 40,7% were diffuse and the other 11,2% were mixed. According to the location, 50% of the tumors were found to be proximal. 41,1% of the tumors were found to be in a low stage (I â IIIA), 44,8% in a high stage (IIIB â IV) and 13,8% were not staged. The imunohistochemical results indicated that KI-67 is the best marker to estimate cellular proliferation in stomach adenocarcinomas. In an independent manner, the tumors showed an 89,3% positivity for KI-67, 62,5% for PCNA, 50% for p53, 60,7% for bcl-2 e 66,7% for c-myc. According to the staging, the difference was significant only to p53 (p = 0,02), with a 66,7% positivity to the tumors in low stage and 16,7% for the ones on a high stage. When evaluated in a combined form, the associations of KI-67+/p53- (p=0,012) (66,67%) and c-myc+/p53- (p=0,02) (63,64%) both for the high stage tumors, were found to be significant. The DNA extraction technique applied to the tumor tissue was found to be satisfactory. For the SSCP analyses, five patients had mutation on the exon 5 (3) and on the exon 7 (2). Based on that, we may conclude that KI-67 is the best marker to access the proliferation of the stomach adenocarcinomas and that there are two proliferation activation pathways: one being dependent and the other independent of the p53 gene.
Na busca de um melhor entendimento da biologia dos tumores, marcadores moleculares relacionados à proliferaÃÃo, resistÃncia e apoptose tÃm sido intensamente pesquisados nos diferentes tipos de cÃncer. Estes marcadores podem auxiliar no estudo de alvos terapÃuticos mais especÃficos para cada tipo de tumor. O cÃncer de estÃmago à a segunda causa de Ãbito mais observado no mundo. No Brasil, este tumor està entre as cinco localizaÃÃes primÃrias mais comuns de Ãbitos por cÃncer, sendo os adenocarcinomas responsÃveis por 95% dos casos. Dessa forma, foi avaliada a expressÃo dos marcadores KI-67, PCNA, p53, bcl-2 e c-myc de forma independente e combinada em adenocarcinomas gÃstricos. TambÃm foi avaliado qual dos marcadores, KI-67 ou PCNA, era mais indicado para acessar a proliferaÃÃo celular. AlÃm disso, foi implantada a tÃcnica de extraÃÃo de DNA de tecido tumoral com CTAB e anÃlise molecular pelo SSCP do gene p53, sendo os resultados positivos comparados com os resultados da imunohistoquÃmica. Os tumores foram coletados em cirurgia, processados e classificados histopatologicamente. Os marcadores foram detectados pelo mÃtodo de imunohistoquÃmica SABP. Foi realizada a extraÃÃo de DNA pelo mÃtodo do CTAB, sendo os Ãxons 5, 7 e 8/9 do gene p53 analisados por SSCP. Algumas amostras foram obtidas de arquivo de biopsia. A faixa etÃria dos pacientes encontrava-se entre 61 e 70 anos de idade, com 48,1% dos tumores do tipo intestinal, 40,7% difusos e 11,2% mistos e com 50% localizados no sÃtio proximal. Em relaÃÃo ao estadiamento, 41,4% dos tumores apresentavam-se no grau baixo (I â IIIA), 44,8% no altorisco (IIIB â IV) e 13,8% sem estadiamento. De acordo com os achados imunohistoquÃmicos, os resultados sugerem que o marcador mais indicado para estimar a proliferaÃÃo celular nos adenocarcinomas gÃstricos à o KI-67. De forma independente os tumores apresentaram positividade em 89,3% para KI-67, 62,5% para PCNA, 50% para p53, 60,7% para bcl-2 e 66,7% e para c-myc. De acordo com o estadiamento, a diferenÃa foi significativa apenas para p53 (p = 0,02), com positividade de 66,7% nos tumores de baixo risco (I â IIIA) e 16,7% nos de altorisco. Quando avaliadas de forma combinada, as associaÃÃes significativas foram entre KI-67+/p53- (p=0,012) nos tumores de alto risco (66,67%) e c-myc+/p53- (p=0,02) tambÃm nos tumores de altorisco (63,64%). A tÃcnica aplicada para a extraÃÃo do DNA do tecido tumoral foi satisfatÃria. Para o SSCP, cinco pacientes apresentaram mutaÃÃo para o Ãxon 5 (3) e Ãxon 7 (2). Com isso, concluÃmos que o marcador mais indicado para acessar a proliferaÃÃo à o KI-67 e que existem duas vias de ativaÃÃo da proliferaÃÃo nos adenocarcinomas gÃstricos: uma dependente de p53 e outra independente de p53.
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Abens, Ryan. "GENE EXPRESSION OF CYTOKINES AND OXIDATIVE STRESS MARKERS IN CTRP3 TRANSGENIC MICE WITH CHRONIC ETHANOL EXPOSURE." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/2.
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Oxidative stress and inflammation are often linked to the prognosis of diseases caused by chronic alcohol consumption. Chronic alcohol consumption plays a key role in brain tissue damage, often leading to the development of cognitive disorders and loss of brain function. In addition to the direct effects of alcohol on brain function, consumption of alcohol can lead to psychosocial stressors such as legal, financial, and interpersonal problems. It has been found that mice that overexpress C1q/Tumor Necrosis Factor-related protein-3 (CTRP3) and exposed to ethanol daily do not die like the mice who did not overexpress CTRP3 and fed the same diet. Although the specific physiological functions regulated by the CTRP family are largely unknown, there is evidence showing that they have diverse biological effects on inflammation, metabolism, and survival signaling in several different types of tissue. Postmortem brain tissue samples were collected from mice that were exposed to ethanol with transgenic overexpression of CTRP3 and from wild type mice that were only exposed to ethanol. Interestingly, previous immunoblotting of the cerebellum and the hippocampus using collected tissue demonstrated that glia activation was present in the CTRP3 overexpressing mice but not in the wild-type ethanol fed mice. This finding suggests that glia cells are either dying in the ethanol fed wild type mice or that CTRP3 protects and prolongs activated glia cells. The current study will determine if markers of oxidative stress and cell viability are altered in the CTRP3 overexpressing mice when compared to wild-type mice at the molecular level. RNA isolation using the Directzol system and cDNA synthesis using punch dissected homogenate tissue collected from the hippocampus was used for this investigation. Gene expression of BDNF, SOD1 and PARP1 in mouse tissue was determined using quantitative PCR. Immunoblotting of a small number of hippocampal tissue using PARP1 was performed. The mice that were CTRP3 overexpressed and fed ethanol will likely exhibit altered gene expression of cytokines and increased oxidative stress gene expression in postmortem hippocampal brain tissue when compared to wild-type ethanol fed mice. The current studies could contribute to the body of knowledge for the development of novel therapies that may alleviate the neuro-inflammatory effects of alcohol use.
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Gainer, Thomas Gregory. "Immune Response Markers are Prevalent in the mRNA Expression Profile of Maturing Dystrophic Murine Skeletal Muscle." Thesis, Virginia Tech, 2005. http://hdl.handle.net/10919/33263.
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Duchenne muscular dystrophy (DMD) is a severe and fatal muscle wasting disease characterized by a high mutation rate in the gene that encodes the membrane-associated protein dystrophin that results in absence of expressed protein. Although the primary genetic defect for DMD is known, the mechanisms that initiate the onset of DMD are not currently understood. This study tested the hypothesis that pathophysiological processes involved in DMD could be identified by the global expression of mRNA in maturing dystrophin- and utrophin-deficient mouse (mdx:utrn-/-) muscles. Two potential dystrophic onset mechanisms targeted for analysis were (1) disrupted expression of calcium handling proteins; and, (2) increased expression of immune response markers.
An mRNA expression profile was developed following isolation of total RNA from control and mdx:utrn-/- triceps surae (TS) muscles at ages 9-10 and 20-21 days using Affymetrix® Mu74Av2 GeneChips®. Compared to control, the mRNA expression profile in mdx:utrn-/- muscles revealed there was a 3-fold increase in the number of gene transcripts differentially expressed more than 2-fold (53 transcripts at ages 9-10 days; 153 at ages 20-21 days). However, there were no changes in the mRNA transcripts for calcium handling proteins. In distinct contrast, there was up-regulation of transcripts that corresponded to an immune response (40 transcripts), extracellular matrix activity (14), and proteolysis (8). Up-regulation of several transcripts corresponded to cytokines and their receptors (11), chemokines and their receptors (5), and lymphoid and myeloid markers (16) suggesting that dystrophic muscle is susceptible to invasion by macrophages, leukocytes, B- and T-cells. These results are consistent with several reports (Spencer et al., 1997; Chen et al., 2000; Porter et al., 2002; Porter et al., 2003a; Porter et al., 2003b; Porter et al., 2004) that indicate the immune system may play an important role in the early pathophysiology of DMD. Understanding the functional aspects of an immune response in DMD onset should lead to more effective therapeutics.Master of Science
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Guglielmino, Maria Rosa. "Studio di macchinari molecolari in ovociti umani." Thesis, Universita' degli Studi di Catania, 2011. http://hdl.handle.net/10761/128.
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Il lavoro presentato in questa tesi ha come oggetto di studio il gamete femminile ed in particolare il trascrittoma dell'ovocita umano.
All'interno di questa linea di ricerca abbiamo:
Caratterizzato il TFIID [1, 2] in condizioni non patologiche per ricercare marcatori molecolari da correlare alla qualita' ovocitaria [3];
Valutato il profilo di espressione dei geni codificanti le proteine del macchinario apoptotico [4] durante l ' invecchiamento riproduttivo;
Valutato la qualita' ovocitaria in risposta a specifici protocolli di congelamento (Vitrificazione) [5].The aim of my PhD thesis was the study of human female germ cells, particularly the transcriptome of mature oocyte. I reported the summary of the obtained results: Characterization of human TFIID in single oocytes in non pathological conditions: new potential molecular markers of oocyte quality; Expression profile of apoptotic machinery genes in human mature oocyte and in cumulus cells in relation to maternal age: molecular basis of competence decrease; Molecular profiling of human oocytes after vitrification.
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Anastassiadis, Konstantinos, and Maria Rostovskaya. "Differential Expression of Surface Markers in Mouse Bone Marrow Mesenchymal Stromal Cell Subpopulations with Distinct Lineage Commitment." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-191602.
Full textAbstract:
Bone marrow mesenchymal stromal cells (BM MSCs) represent a heterogeneous population of progenitors with potential for generation of skeletal tissues. However the identity of BM MSC subpopulations is poorly defined mainly due to the absence of specific markers allowing in situ localization of those cells and isolation of pure cell types. Here, we aimed at characterization of surface markers in mouse BM MSCs and in their subsets with distinct differentiation potential. Using conditionally immortalized BM MSCs we performed a screening with 176 antibodies and high-throughput flow cytometry, and found 33 markers expressed in MSCs, and among them 3 were novel for MSCs and 13 have not been reported for MSCs from mice. Furthermore, we obtained clonally derived MSC subpopulations and identified bipotential progenitors capable for osteo- and adipogenic differentiation, as well as monopotential osteogenic and adipogenic clones, and thus confirmed heterogeneity of MSCs. We found that expression of CD200 was characteristic for the clones with osteogenic potential, whereas SSEA4 marked adipogenic progenitors lacking osteogenic capacity, and CD140a was expressed in adipogenic cells independently of their efficiency for osteogenesis. We confirmed our observations in cell sorting experiments and further investigated the expression of those markers during the course of differentiation. Thus, our findings provide to our knowledge the most comprehensive characterization of surface antigens expression in mouse BM MSCs to date, and suggest CD200, SSEA4 and CD140a as markers differentially expressed in distinct types of MSC progenitors.
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Anastassiadis, Konstantinos, and Maria Rostovskaya. "Differential Expression of Surface Markers in Mouse Bone Marrow Mesenchymal Stromal Cell Subpopulations with Distinct Lineage Commitment." Public Library of Science, 2012. https://tud.qucosa.de/id/qucosa%3A29135.
Full textAbstract:
Bone marrow mesenchymal stromal cells (BM MSCs) represent a heterogeneous population of progenitors with potential for generation of skeletal tissues. However the identity of BM MSC subpopulations is poorly defined mainly due to the absence of specific markers allowing in situ localization of those cells and isolation of pure cell types. Here, we aimed at characterization of surface markers in mouse BM MSCs and in their subsets with distinct differentiation potential. Using conditionally immortalized BM MSCs we performed a screening with 176 antibodies and high-throughput flow cytometry, and found 33 markers expressed in MSCs, and among them 3 were novel for MSCs and 13 have not been reported for MSCs from mice. Furthermore, we obtained clonally derived MSC subpopulations and identified bipotential progenitors capable for osteo- and adipogenic differentiation, as well as monopotential osteogenic and adipogenic clones, and thus confirmed heterogeneity of MSCs. We found that expression of CD200 was characteristic for the clones with osteogenic potential, whereas SSEA4 marked adipogenic progenitors lacking osteogenic capacity, and CD140a was expressed in adipogenic cells independently of their efficiency for osteogenesis. We confirmed our observations in cell sorting experiments and further investigated the expression of those markers during the course of differentiation. Thus, our findings provide to our knowledge the most comprehensive characterization of surface antigens expression in mouse BM MSCs to date, and suggest CD200, SSEA4 and CD140a as markers differentially expressed in distinct types of MSC progenitors.
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Harding, Charles P. "In Vitro Simulation of Microgravity Induced Muscle Loss Successfully Increases Expression of Key In Vivo Atrophy Markers." DigitalCommons@USU, 2019. https://digitalcommons.usu.edu/etd/7436.
Full textAbstract:
Muscle loss from lack of activity is a serious issue for immobilized patients on Earth and in human spaceflight, where the low gravity environment prevents normal muscle activity. Simulating muscle loss in cultured cells is an important step in understanding how this condition occurs. This work evaluates different means of simulating muscle loss and selects the one that most closely mimics the cellular responses seen in animals and humans.
To simulate the microgravity environment of spaceflight, mouse skeletal muscle cells were grown in a rotary cell culture system (RCCS). Growing the cells within a natural gelled substrate was compared against growing them on the surface of small plastic beads. Changes after culture under simulated microgravity were characterized by assessing proteins and genes known to change during muscle loss. The structure of the cells was also evaluated by microscopy.
The mouse skeletal muscle cells grown on plastic beads in the RCCS had significant changes in multiple key genes associated with muscle loss and demonstrated physical characteristics expected of mature tissue in live animals. This model is a valuable platform for exploring muscle loss mechanisms and testing new drugs.
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Huffman, Derek M. "Calorie restriction, exercise and body fat effects on cancer and markers of longevity /." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2009r/huffman.pdf.
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Vaitkienė, Grigaitė Paulina. "A study of tumor suppressor gene expression and promoter methylation for the identification of prognostic markers in glioblastoma." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2013~D_20130419_111627-63926.
Full textAbstract:
Glioblastoma (GBM) is the most common primary brain tumor in adults. This study attempted to
identify the genes potentially regulated by promoter methylation in GBM. Therefore, we analyzed
the expression of COX7A1, SPINT1, AREG, NPTX2, and KRT81 in glioblastomas and human brain
tissue and investigated if there were any associations between the expression and methylation of
these genes. Moreover, we aimed to determine the methylation frequency of 11 genes (AREG,
CASP8, CD81, DcR1, DR4, GATA4, GATA6, hMLH1, NPTX2, TES, and TFPI2) promoters in 100
patients with glioblastoma multiforme and to evaluate the associations between patients’ clinical
characteristics and prognostic value. The methylation status of the following 4 gene promoters
was significantly related to patients’ survival after surgery: AREG, CASP8, GATA6 and TFPI2.
Identification of the methylation status of these genes could be one of the objective criteria in the
prognosis of disease course in patients with glioblastoma and could supplement the list of already
known epigenetic markers. The methylation status of a combination of 6 genes (AREG, CASP8,
DR4, GATA4, GATA6, and TFPI2) was found to be a more accurate independent prognostic factor
associated with patients’ survival after surgery when compared with the methylation status of
individual genes. The molecular classification of GBM according to the methylation profile of a
combination of these 6 genes could help clinicians tailor an appropriate treatment... [to full text]Glioblastoma (GBM) yra vienas labiausiai paplitusių ir agresyviausių pirminių galvos smegenų auglių. Siekiant nustatyti molekulinius žymenis, susijusius su GBM vystymusi, diagnoze ir prognoze, buvo atlikta 14 genų (AREG, CASP8, CD81, COX7A1, DcR1, DR4, GATA4, GATA6, hMLH1, KRT81, NPTX2, SPINT1, TES ir TFPI2) promotorių metilinimo analizė. Buvo nustatyti naviką slopinančių genų promotorių metilinimo dažniai, ryšiai su klinikinėmis sergančiųjų GBM charakteristikomis ir prognozinė vertė. Disertacinio darbo metu nustatyta, kad AREG ir NTPX2 genų raiška susijusi su šių genų promotorių metilinimu, tuo tarpu COX7A1, KRT81 ir SPINT1 genų raiškos skirtumai nėra susiję su šių genų promotorių metilinimu. Naujų epigenetinių žymenų tyrimai 100 GBM pavyzdžių parodė navikų epigenetinį heterogeniškumą ir įvairų tirtų genų promotorių metilinimo dažnį. Nustatyta, kad AREG, CASP8, GATA6 ir TFPI2 genų promotorių metilinimas statistiškai patikimai susijęs su išgyvenimo trukme po operacijos. Šių genų promotoriaus metilinimo nustatymas gali būti vienas iš objektyvių kriterijų prognozuojant pacientų ligos eigą ir papildyti jau nustatytų epigenetinių žymenų sąrašą. Buvo sudarytas, suminis šešių genų (AREG, CASP8, DR4, GATA4, GATA6 ir TFPI2) derinys, kuris yra tikslesnis nepriklausomas prognozinis veiksnys, susijęs su išgyvenimo trukme po operacijos lyginant su atskirų genų promotorių metilinimu. GBM molekulinis tipavimas pagal šių šešių genų derinį galėtų padėti parenkant gydymo strategiją.
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Mbu, Desiree Lem. "Expression of circulating Microrna’s (Mirnas) in blood of mixed ancestry subjects with glucose intolerance." Thesis, Cape Peninsula University of Technology, 2018. http://hdl.handle.net/20.500.11838/2816.
Full textAbstract:
Thesis (MSc (Biomedical Sciences))--Cape Peninsula University of Technology, 2018.Background: Early detection of individuals who are at risk of developing Glucose Intolerance would decrease the morbidity and mortality associated with this disease. MicroRNA is one of the most widely studied biomolecules involved in epigenetic mechanisms, hence it offers unique opportunities in this regard. Circulating microRNAs are associated with disease pathogenesis during the asymptomatic stage of disease. This has therefore attracted a lot of attention as a potential biomarker for identifying individuals who have an increased risk of developing Glucose Intolerance. The identification of high risk biomarkers for Glucose Intolerance will go a long way to eliminate the possible complications that arise due to late diagnosis and treatment of Glucose Intolerance. This could ultimately lead to better ways to prevent, manage and control the Glucose Intolerance epidemic that is rampant worldwide. The aim of the study is to investigate expression of circulating microRNA’s in blood of mixed ancestry subjects with glucose intolerance. Methods: A quantitative cross-sectional study design involving 36 individuals [who were age, gender and BMI (Body Mass Index) matched] from a total population of 1989 participants of mixed ancestry descent, residing in Bellville South, South Africa was used. Participants were classified as controls (normoglycemic), pre-diabetic (preDM) and diabetic (DM) (screen detected diabetic) according to WHO criteria of 1998. MicroRNAs were extracted from serum using the Qiagen miRNeasy Serum/Plasma Kit (ThermoFisher). The purified micro RNAs were reverse-transcribed to cDNA (complementary deoxyribonucleic acid) using the Qiagen RT2 First Strand Kit. Then, using Qiagen miScript SYBR Green PCR kit and miScript miRNA PCR arrays (ThermoFisher), the real time polymerase chain reaction was done to determine the expression profile the circulating micro RNAs present in the serum of the participants. Results: The 36 participants were evenly divided into 3 groups of 12 participants each as mentioned earlier. There were significant differences between groups in the waist (cm) (p=0.0415) and waist/hip ratio (p=0.0011) with highest values in the DM group and lowest in the normal group. Clinical parameters varied significantly according to glycemic status. As expected, the FBG (mmol/L) (p<0.0001), 2 HRs Post Glucose (mmol/L) (p<0.0001), HbA1c (%) (p=0.0009), Fasting Insulin (mIU/L) (p=0.0039), were all highest in the DM and lowest in the control group. In contrast, the 2 HRs Post Insulin (mIU/L) (p = 0.0027) was highest in the preDM group and lowest in the normal group, while the Glucose/Insulin ratio (p=0.0477) was highest in the normal group and lowest in the preDM group. Triglycerides (mmol/L) (p=0.0043) and Total Chol (mmol/L) (p=0.0429) were significantly increased through the three groups, with highest values in the DM group and lowest in the normal group. Furthermore, 12 of the 84 miRNAs studied were expressed through all the 3 groups and they exhibited both inverse and positive correlations between the clinical parameters, especially the glucose parameters (Fasting blood glucose, 2 hours post glucose, Fasting blood insulin, 2 hours post insulin and Glycated Hemoglobin).
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Hjalmar, Viktoria. "Chronic leukemic B-cell disorders and trisomy 12 : a study of surface markers, protein expression and clinical course /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4664-7/.
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Bohl, Stephan [Verfasser]. "Gene expression profiling based identifications of potential prognostic molecular markers in decitabine treated acute myeloid leukemia / Stephan Bohl." Ulm : Universität Ulm, 2016. http://d-nb.info/1101578297/34.
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Ramberg, Anna. "Expression of hormone receptors and markers for metastatic potential in relation to tumor associated macrophages in breast cancer." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-48433.
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Boateng, Edward. "Temporal expression of neurochemical markers in primary sensory neurones in traumatic and non-traumatic models of neuropathic pain." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/11162.
Full textAbstract:
Introduction: Expression of neurochemical markers in dorsal root ganglion (DRG) has been shown to underlie nerve injury induced neuropathic pain and are usually examined once post injury in rodent models. Here I hypothesize that neurochemical markers are expressed differentially at various time points post nerve injury and that expression of these markers differ between traumatic and non-traumatic models of neuropathic pain, thus reflecting variations in pathophysiology. In two different rat models of neuropathic pain, namely, the tibial nerve transection (TNT) and the d4T (HIV antiretroviral drug) associated toxic neuropathy; immunohistochemical labelling was used to determine the expression of various neurochemical markers across time. Double labelling with peripherin or NF-200 (labels small and large neurons respectively) and a cell size analysis were conducted to validate cellular phenotype. Pain behaviour was measured in vivo using mechanical and thermal hypersensitivity assays. To confirm tibial nerve distribution in the DRGs, Fluorogold retrograde labelling was performed. I also explored the effect of the omega-3 polyunsaturated fatty acid dicosahexonoic acid (DHA) on TNT associated mechanical hypersensitivity and inflammation, as previous studies have shown DHA to be both anti-inflammatory and neuroprotective in animal models of spinal cord injury and stroke, and therefore could be relevant in peripheral nerve injury. Results: [Table of results appears here. To view, please open pdf attachment] From day 7, TNT rats developed mechanical hypersensitivity (↓62% from baseline at peak, day 28). Rats injected with d4T exhibited bilateral hind paw mechanical hypersensitivity (↓~47% from baseline at peak, day 22), but failed to exhibit any neurochemical changes in the DRG such as that observed in TNT injury. Seven days following Fluorogold injection into the tibial nerve of naive rats, labelling was identified in the L4 (38.5%) and L5 (27.5%) DRGs. Since DHA did not alter TNT induced mechanical hypersensitivity, key neurochemical markers were not evaluated. Investigations examined the potential of DHA to modulate the DRG macrophage response, and revealed no differences compared to saline controls at day 28 post TNT injury. Conclusion: The results of the study demonstrate completely different expression patterns of neurochemical markers following TNT injury and treatment with d4T, and highlight the mechanistic difference between nerve trauma and antiretroviral associated neuropathic pain.
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Bangcaya, Josette Pesayco. "IGF-I, IGF-II and IGF-IR expression as molecular markers for egg quality in mullet and grouper." Thesis, Queensland University of Technology, 2004. https://eprints.qut.edu.au/16003/1/Josette_Bangcaya_Thesis.pdf.
Full textAbstract:
Common measures of egg quality have been survival to specific developmental stages, higher hatching rate of fertilized eggs and final production of fry. Determinants of egg quality are variable among and between teleost species and no common unified criteria have been established. Maternally inherited genes influence egg quality and early embryo development is partially programmed by the messenger ribonucleic acid (mRNA). Among the genes, the insulin family is important for growth functions and the presence of their transcripts in the ovary, oocytes and embryos implies their involvement during the reproductive process and their relevance to egg quality. The insulin-like growth factor (IGF) system has three components, the ligands IGF-I and II, the IGFBPs (insulin-like growth factor binding proteins) and the IGF receptors that mediate biological activity of the ligands. Vitellogenin (Vtg) is the major source of nutrients for the developing embryo and elevated levels in female fish plasma signals gonadal development preceding spawning. In oviparous fish where the developing embryo is dependent on the stored food in the yolk, vitellogenin levels in the egg could indicate its capability to support embryonic growth.
This study aimed to develop molecular tools, specifically probes for IGF-I, IGF-II and IGF-IR, for the evaluation of fish egg quality. These probes would be used to determine expression levels of IGF-I, IGF-II and IGF-IR during egg development to assess their potential as molecular indicators for egg quality. In addition, this study also aimed to establish an enzyme-linked immunoassay (ELISA) for quantifying Vtg in fish eggs and determine if differences in Vtg levels could be linked to fertilization and hatching success.
Through reverse-transcription polymerase chain reaction (RT-PCR) putative complementary deoxyribonucleic acid (cDNA) fragments of IGF-I, IGF-II and IGF-IR were cloned and sequenced from mullet (Mugil cephalus) and grouper (Epinephelus coioides). The relative expression ratio of the three genes in the eggs of mullet and grouper were assayed by quantitative PCR (QPCR) and calculated using the Pfaffl method (Pfaffl, 2001). Levels of vitellogenin in different batches of mullet eggs were quantified by ELISA.
Spawned eggs of grouper were grouped into low (<60%) or high (>60%) fertilization rate (FR) and the fertilized eggs that were incubated until hatching were grouped into medium (>90%) or high (>90%) hatching rate (HR). Samples were categorized into sinking eggs, late embryo and hatched larvae. Relative expression ratio of IGF-II was significantly high (P<0.01) compared to IGF-I and IGF-IR in all samples examined. All three genes were strongly expressed in sinking eggs compared to either late embryo or hatched larvae. However, there was no significant interaction effect between the genes and the samples analyzed. Mullet samples all came from a high FR and high HR group and were categorized into sinking, multicell stage, blastula, gastrula, late embryo and hatched larvae. There was a significant interaction effect (P<0.01) between gene and stage, showing that genes are differentially expressed during embryonic development. IGF-II was strongly expressed relative to the other genes in all stages examined and was highest during the gastrula stage.
Vtg levels were examined in mullet oocytes and egg samples that were grouped into 4; oocytes from females that subsequently spawned, had fertilized eggs which hatched (Group A); oocytes from females that did not spawn, therefore no fertilization and no hatching (Group B); eggs that were stripped, artificially fertilized but no hatching (Group C); and eggs that were spawned, assumed to be fertilized but did not hatch (Group D). Group A showed a trend of higher Vtg levels than the other three but this result was not statistically significant.
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Bangcaya, Josette Pesayco. "IGF-I, IGF-II and IGF-IR expression as molecular markers for egg quality in mullet and grouper." Queensland University of Technology, 2004. http://eprints.qut.edu.au/16003/.
Full textAbstract:
Common measures of egg quality have been survival to specific developmental stages, higher hatching rate of fertilized eggs and final production of fry. Determinants of egg quality are variable among and between teleost species and no common unified criteria have been established. Maternally inherited genes influence egg quality and early embryo development is partially programmed by the messenger ribonucleic acid (mRNA). Among the genes, the insulin family is important for growth functions and the presence of their transcripts in the ovary, oocytes and embryos implies their involvement during the reproductive process and their relevance to egg quality. The insulin-like growth factor (IGF) system has three components, the ligands IGF-I and II, the IGFBPs (insulin-like growth factor binding proteins) and the IGF receptors that mediate biological activity of the ligands. Vitellogenin (Vtg) is the major source of nutrients for the developing embryo and elevated levels in female fish plasma signals gonadal development preceding spawning. In oviparous fish where the developing embryo is dependent on the stored food in the yolk, vitellogenin levels in the egg could indicate its capability to support embryonic growth. This study aimed to develop molecular tools, specifically probes for IGF-I, IGF-II and IGF-IR, for the evaluation of fish egg quality. These probes would be used to determine expression levels of IGF-I, IGF-II and IGF-IR during egg development to assess their potential as molecular indicators for egg quality. In addition, this study also aimed to establish an enzyme-linked immunoassay (ELISA) for quantifying Vtg in fish eggs and determine if differences in Vtg levels could be linked to fertilization and hatching success. Through reverse-transcription polymerase chain reaction (RT-PCR) putative complementary deoxyribonucleic acid (cDNA) fragments of IGF-I, IGF-II and IGF-IR were cloned and sequenced from mullet (Mugil cephalus) and grouper (Epinephelus coioides). The relative expression ratio of the three genes in the eggs of mullet and grouper were assayed by quantitative PCR (QPCR) and calculated using the Pfaffl method (Pfaffl, 2001). Levels of vitellogenin in different batches of mullet eggs were quantified by ELISA. Spawned eggs of grouper were grouped into low (<60%) or high (>60%) fertilization rate (FR) and the fertilized eggs that were incubated until hatching were grouped into medium (>90%) or high (>90%) hatching rate (HR). Samples were categorized into sinking eggs, late embryo and hatched larvae. Relative expression ratio of IGF-II was significantly high (P<0.01) compared to IGF-I and IGF-IR in all samples examined. All three genes were strongly expressed in sinking eggs compared to either late embryo or hatched larvae. However, there was no significant interaction effect between the genes and the samples analyzed. Mullet samples all came from a high FR and high HR group and were categorized into sinking, multicell stage, blastula, gastrula, late embryo and hatched larvae. There was a significant interaction effect (P<0.01) between gene and stage, showing that genes are differentially expressed during embryonic development. IGF-II was strongly expressed relative to the other genes in all stages examined and was highest during the gastrula stage. Vtg levels were examined in mullet oocytes and egg samples that were grouped into 4; oocytes from females that subsequently spawned, had fertilized eggs which hatched (Group A); oocytes from females that did not spawn, therefore no fertilization and no hatching (Group B); eggs that were stripped, artificially fertilized but no hatching (Group C); and eggs that were spawned, assumed to be fertilized but did not hatch (Group D). Group A showed a trend of higher Vtg levels than the other three but this result was not statistically significant.
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Da, Rocha Tomás Gil. "Gene Expression Markers of Proliferation and Differentiation in Cancer & The Extent of Prognostic Signals in the Cancer Transcriptome." Doctoral thesis, Universite Libre de Bruxelles, 2016. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/235915.
Full textAbstract:
Le cancer est un groupe de maladies génétiques opérationnellement défini par uneprolifération cellulaire incontrôlée, impliquant une défaillance del'homeostasie de l'organisme. La recherche sur le cancer vise à fournir desoutils diagnostics précis et des traitements ajustés pour chacune de cesmaladies. La technologie microarray permet la quantification de l'expression detous les produits de transcription du génome humain et constitue donc un outilpour mieux comprendre la nature polygénique du cancer. La technologiemicroarray permet à la fois de découvrir de nouvelles classes de cancers et deprédire l'issue de maladie en fonction de profils d'expression préalables. Enoutre, l'utilisation de signatures d'expression géniques en tant que marqueursreprésentatifs de certains processus physiologiques moléculaires permetl'emploi de données microarray pour tester des hypothèses biologiques.Cette dissertation a deux objectifs: (a) établir la mesure dans laquelledes marqueurs d'expression génique de la différenciation et de la proliférationcellulaire peuvent contribuer à la classification des maladies cancéreuses; et(b) d'évaluer l'étendue des signaux pronostiques dans les transcriptomescancéreux.Nous avons mis au point une méthode objective pour extraire des signatures dedifférentiation organe-spécifiques à partir de données d'expression génique.Nous avons ensuite démontré qu'une signature génique de différentiationtissu-spécifique est capable de distinguer avec précision entre des sous-typeshistologiques de difficile classification dans un modèle thyroïdien. Ceci faitpreuve du potentiel valeur clinique et diagnostique des signatures dedifférentiation dans le domaine oncologique.Nous montrons aussi qu'une fraction non négligeable des transcriptomes cancéreuxest capable de prédire l'issue des respectives maladies, à la suite d'uneanalyse systématique de 114 cohortes de profiles d'expression cancéreuxenglobant 19 types de cancers différents. Cet observation est probablement liéeà une vaste structure de corrélation parmis les profils d'expression cancéreux,partiellement expliquée par des variables techniques et biologiques. Cetteevidence met en cause l'utilisation généralisée d'associations statistiquesentre des marqueurs d'expression géniques et les issues de chaque maladie parmisplusieurs patients afin d'en déduire l'implication de mécanismes biologiquesparticuliers dans la progression du cancer.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished
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Nizza, Suzanne Josette Taghap. "The Role of Dendritic Cell Subsets in Cross-presentation and Stimulation of Homing Marker Expression." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11224.
Full textAbstract:
Topical antigen (Ag) application mimics natural Ag exposure across the skin. Soluble Ag introduced through this route requires cross-presentation by dendritic cells (DCs) to generate CD8 T cell responses, including skin-homing T cells. DCs process Ag for display to other immune cells, and stimulate T cells to release cytokines or directly lyse infected cells. Some T cells are further stimulated to express homing markers allowing them to enter non-lymphoid tissue such as the skin or the gut.
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Velázquez-Fernández, David. "Differential RNA expression in benign and malignant adrenocortical tumours /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-578-X/.
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Garrett, Ian D. F. "Gene Expression Life History Markers in a Hatchery and a Wild Population of Young-of-the-Year Oncorhynchus mykiss." PDXScholar, 2013. https://pdxscholar.library.pdx.edu/open_access_etds/1445.
Full textAbstract:
Life history within a single species can vary significantly. Many of these differences are associated with varying environmental conditions. Understanding what environmental conditions cue alternate life histories within a single species has been researched extensively. In salmonid fishes, more than almost any other group, varying environmental conditions give rise to individuals within species that take markedly different life history trajectories.
Oncorhynchus mykissis a species of salmonid native to the Pacific Northwest region of North America. This species has two life history forms, anadromous and resident. The anadromous form spends a portion of its life in ocean while the resident life history form completes its entire life history in freshwater. Until the decision to migrate and morphological changes associated with smoltification occur, the two life history variants of this species are indistinguishable from each other. This ambiguity in juvenile O. mykiss morphology presents challenges for conservation managers charged with protecting and increasing threatened O. mykiss populations around the Pacific Northwest because conservation efforts cannot be evaluated until juvenile fish make the decision to migrate.
Microarray gene expression analysis was used to profile gene expression in juvenile populations of wild and hatchery O. mykiss to identify gene expression variation associated with alternate life history variants. This analysis identified 8 DNA sequences present in both brain and gill tissues that differ in expression in rainbow trout and steelhead hatchery stocks. Differential expression as quantified by microarrays was validated with quantitative real-time PCR. Lastly, the expression of these putative life history markers was preliminarily evaluated in a wild population of O. mykiss at sample locations in the South Fork John Day River Basin, Oregon with known ratios of juvenile anadromous and resident fish.
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Woodward, Eleanor. "The use of gene expression profiling to identify novel minimal residual disease markers (MRD) in acute myeloid leukaemia (AML)." Thesis, Cardiff University, 2010. http://orca.cf.ac.uk/55179/.
Full textAbstract:
Acute myeloid leukaemia (AML) is a heterogeneous disorder characterised by the accumulation of immature haematopoietic cells blocked at various stages of differentiation. Despite improved survival rates over the past decade, relapse occurs in approximately 70% patients undergoing chemotherapy. A potential reason for this is that current clinical protocols do not take account of the level of residual disease present at remission. Therefore, one strategy to reduce relapse rates is to monitor minimal residual disease and continue to treat until the patient is minimal residual disease negative. Current minimal residual disease markers are available for patients with characterised fusion genes but approximately 50% of patients have no detectable chromosomal aberration and therefore are without markers. Gene expression profiling is a powerful tool for disease classification, prognosis and therapeutic predictions. This study aimed to investigate the use gene expression profiling to identify novel minimal residual disease markers for specific AML sub-groups. Patient diagnostic samples were profiled to identify genes specific to AML patients with a favourable translocation in order to establish the "proof-of-principle". Several genes identified were followed in patient diagnostic and follow- up samples and compared to the markers currently used. Continuing with normal karyotype AML, genes were identified as specific to this sub-group. Several homeobox (HOX) genes and the Wilms' tumour (WT1) gene were identified and their MRD levels followed in diagnostic and follow-up samples. Only WT1 identified as specific to normal karyotype AML met the necessary criteria to be an MRD marker. Although the majority of genes selected from the GEP in this study proved unsuitable as markers, the identification and validation of a marker already used for MRD monitoring, WT1, demonstrates the ability of gene expression profiling to identify potential minimal residual disease markers in normal karyotype AML.
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Johansson, Petronella. "Characterisation of putative dendritic cell markers in salmonids and modulation of gene expression following stimulation with interleukin-4/13." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=216323.
Full textAbstract:
Dendritic cells (DCs) are leukocytes specialized in antigen presentation. As competent stimulators of naive T lymphocytes, they link the innate and adaptive immune responses of vertebrates. The RAG-mediated adaptive immune system appeared approximately 500 million years ago in jawed fish and a number of studies suggest that DCs exist in bony and cartilaginous fish. However, the exact role of DCs in the fish immune system is not determined and questions remain as to whether a cell type truly homologous to DCs in homeotherms does exist. My project aimed to identify potential DCs surface markers (CD209A and LAMP3) in rainbow trout (Oncorhynchus mykiss) leukocytes for evaluation of the expression patterns by qRT-PCR under different conditions and stimuli, in vitro and in vivo. Another goal was to validate and evaluate the specificity of a produced anti-trout CD209A polyclonal antibody to further characterise antigen presenting cells (APCs) in fish. The methodology was to look for up-regulation of the predicted markers together with other markers known to be expressed by DCs in mammals and to evaluate at the mRNA and protein expression level after in vitro stimulation of trout primary leukocytes with trout rIL-4/13. Trout CD209A and LAMP3 mRNA was expressed in the main lymphoid organs of fish and could be modulated with microbial mimics. Upon in vitro stimulation of trout primary leukocytes with trout rIL-4/13, trout CD209A mRNA expression was up-regulated together with both CD83 and the MHC class II chain known to be expressed by mammalian DCs. In addition, CD209A protein expression was highly induced by trout rIL-4/13. Taken together, these results suggests that the characterisation of DCs in trout with tools such as transcript evaluation of surface markers and the anti-trout CD209A antibody, could help to more precisely define these leukocyte subsets. These findings could have further impact on fish vaccine improvements and be of importance for the aquaculture industry, by optimising stimulation of adaptive immunity.