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Serial Analysis (serial + analysis)
Selected AbstractsUnveiling the molecular basis of intrinsic skin aging,INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 5 2005O. Holtkötter Synopsis The process of skin aging is a combination of an extrinsic and intrinsic aspect, and knowing the molecular changes underlying both is a prerequisite to being able to effectively counter it. However, despite its importance for a deeper understanding of skin aging as a whole, the process of intrinsic skin aging in particular has barely been investigated. In this study, the molecular changes of intrinsic skin aging were analyzed by applying ,Serial Analysis of Gene Expression' (SAGETM) to skin biopsies of young and aged donors. The analysis resulted in several hundred differentially expressed genes with varying statistical significance. Of these, several genes were identified that either have never been described in skin aging before (e.g. APP) or have no identified function, e.g. EST sequences. This is the first time that intrinsic skin aging has been analyzed in such a comprehensive manner, offering a new and partially unexpected set of target genes that have to be analyzed in more detail in terms of their contribution to the skin aging process. Résumé Le mécanisme de vieillissement de la peau repose sur un ensemble de phénomènes intrinsèques et extrinsèques. La connaissance des modifications moléculaires s'y rattachant est un pré requis pour tenter de le combattre. Cependant, malgré son importance pour une meilleure connaissance du vieillissement cutané dans son ensemble, le mécanisme du vieillissement cutané intrinsèque, n'a été que peu étudié. Dans cette étude, les changements moléculaires du vieillissement cutané intrinsèque ont été analysés à l'aide de la technique SAGETM, Serial Analysis of Gene Expression , appliquée à des biopsies de peau de donneurs jeunes et âgés. L'analyse montre plusieurs centaines de gènes exprimés de façon statistiquement différente. Parmi ceux-ci, plusieurs gènes n'ayant jamais été décrits dans le vieillissement cutané (par exemple l'amyloid precursor protein), ou ne possédant pas de fonction connue, par exemple les séquences EST, ont été identifiés. C'est la première fois que le vieillissement intrinsèque de la peau a été analysé de manière aussi approfondie; on découvre une nouvelle série de gènes cibles en partie inattendus dont la contribution au mécanisme du vieillissement de la peau doit être analysée plus en détails. [source] Acute Activation of Hippocampal Glucocorticoid Receptors Results in Different Waves of Gene Expression Throughout TimeJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2006M. C. Morsink Abstract Several aspects of hippocampal cell function are influenced by adrenal-secreted glucocorticoids in a delayed, genomic fashion. Previously, we used Serial Analysis of Gene Expression to identify glucocorticoid receptor (GR)-induced transcriptional changes in the hippocampus at a fixed time point. However, because changes in mRNA levels are transient and most likely precede the effects on hippocampal cell function, the aim of the current study was to assess the transcriptional changes in a broader time window by generating a time curve of GR-mediated gene expression changes. Therefore, we used rat hippocampal slices obtained from adrenalectomised rats, substituted in vivo with low corticosterone pellets, predominantly occupying the hippocampal mineralocorticoid receptors. To activate GR, slices were treated in vitro with a high (100 nM) dose of corticosterone and gene expression was profiled 1, 3 and 5 h after GR-activation. Using Affymetrix GeneChips, a striking pattern with different waves of gene expression was observed, shifting from exclusively down-regulated genes 1 h after GR-activation to both up and down regulated genes 3 h after GR-activation. After 5 h, the response was almost back to baseline. Additionally, real-time quantitative polymerase chain reaction was used for validation of a selection of responsive genes including genes involved in neurotransmission and synaptic plasticity such as the corticotropin releasing hormone receptor 1, monoamine oxidase A, LIMK1 and calmodulin 2. This permitted confirmation of GR-responsiveness of 15 out of 18 selected genes. In conclusion, direct activation of GR in hippocampal slices results in transient changes in gene expression. The pattern in which gene expression was modulated suggests that the fast genomic effects of glucocorticoids may be realised via transrepression, preceding a later wave of transactivation. Furthermore, we identified a number of interesting candidate genes which may underlie the glucocorticoid-mediated effects on hippocampal cell function. [source] Life history of a mule (c. 160 AD) from the Roman fort Biriciana/Weißenburg (Upper Bavaria) as revealed by serial stable isotope analysis of dental tissuesINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 2 2010T. E. Berger Abstract The presence of the osseous remains of at least four mules in a garbage dump at the Roman fort of Biriciana near the town of Weißenburg, Upper Bavaria, dating to c. 160 AD, raised the question as to whether mule breeding was already performed to the north of the Alps during the Middle Roman Empire, or whether these animals still had to be imported from the Mediterranean. Serial analyses of the dental enamel and dentine of a lower fourth premolar and the surrounding alveolar bone of a mandible of a mule in terms of stable strontium isotopic ratios of the apatite, and stable carbon and oxygen isotope ratios of the structural carbonate, were carried out to test whether this individual moved long distances during its lifetime. Since isotopic ratios obtained by serial analysis can be correlated with consecutive ontogenetic stages, it can be assumed that this particular individual experienced significant changes in terms of diet and environmental parameters after its eighth year of life. These changes included a period of residence in a region of high altitude, most likely the Alps considering the location of the Roman fort where the mule was found. The isotopic data obtained do not contradict the assumption that this animal was bred and raised in northern Italy, to frequent later in its adult life the Alps and finally perish at Biriciana/Weißenburg. Copyright © 2008 John Wiley & Sons, Ltd. [source] Factors affecting the time of onset of resorption in avulsed and replanted incisor teeth in childrenDENTAL TRAUMATOLOGY, Issue 5 2001M. Donaldson Abstract , Resorption is the main reason for loss of replanted teeth. The outcome examined in this study is the timing of the onset of resorption. The effect of dichotomised dry and wet time intervals as well as the presence of additional crown damage and of contamination were determined. Of 84 replanted teeth, 67.5% developed resorptions. Twenty-eight had detectable additional crown damage with a more rapid onset being seen in these cases (P=0.009). The critical limit for dry time was 15 min (P=0.038) and significant differences persisted for greater limits also. Serial analysis of the association between the time of onset of root resorption and dichotomised wet time variables failed to yield any significant associations. There was visible contamination detected in 32 teeth and these exhibited a more rapid onset of resorption than the other cases (P=0.030). Teeth with inflammatory root resorption (12.8%) had a more rapid onset of resorption than those that developed replacement resorption (54.7%) (P<0.001). It is concluded that the risk of early resorption is increased in teeth that have additional damage or have contamination, or are kept in dry conditions for longer than 15 min. [source] Annexin A1 subcellular expression in laryngeal squamous cell carcinomaHISTOPATHOLOGY, Issue 6 2008V A F Alves Aims:, Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. Methods and results:, Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. Conclusions:, ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases. [source] Transcriptome dissection of gastric cancer: Identification of novel diagnostic and therapeutic targets from pathology specimensPATHOLOGY INTERNATIONAL, Issue 3 2009Wataru Yasui Gastric cancer is the fourth most common malignancy in the world, and mortality due to gastric cancer is second only to that from lung cancer. ,Transcriptome dissection' is a detailed analysis of the entire expressed transcripts from a cancer, for the purpose of understanding the precise molecular mechanism of pathogenesis. Serial analysis of gene expression (SAGE) is a suitable technique for performing transcriptome dissection. Gastric cancers of different stages and histology were analyzed on SAGE, and one of the largest gastric cancer SAGE libraries in the world was created (GEO accession number GSE 545). Through SAGE, many candidate genes have been identified as potential diagnostic and therapeutic targets for the treatment of gastric cancer. Regenerating islet-derived family, member 4 (Reg IV) participated in 5-fluorouracil (5-FU) resistance and peritoneal metastasis, and its expression was associated with an intestinal phenotype of gastric cancer and with endocrine differentiation. GW112 expression correlated with advanced tumor stage. Measurement of Reg IV and GW112 levels in sera indicated a sensitivity of 57% for detection of cancer. SPC18 participated in tumor growth and invasion through transforming tumor growth factor-, upregulation. Palate, lung, and nasal epithelium carcinoma-associated protein (PLUNC) was a useful marker for gastric hepatoid adenocarcinoma. Expression of SOX9, HOXA10, CDH17, and loss of claudin-18 expression were associated with an intestinal phenotype of gastric cancer. Information obtained from transcriptome dissection greatly contributes to diagnosis and treatment of gastric cancer. [source] Bayesian Shrinkage Estimation of the Relative Abundance of mRNA Transcripts Using SAGEBIOMETRICS, Issue 3 2003Jeffrey S. Morris Summary. Serial analysis of gene expression (SAGE) is a technology for quantifying gene expression in biological tissue that yields count data that can be modeled by a multinomial distribution with two characteristics: skewness in the relative frequencies and small sample size relative to the dimension. As a result of these characteristics, a given SAGE sample may fail to capture a large number of expressed mRNA species present in the tissue. Empirical estimators of mRNA species' relative abundance effectively ignore these missing species, and as a result tend to overestimate the abundance of the scarce observed species comprising a vast majority of the total. We have developed a new Bayesian estimation procedure that quantifies our prior information about these characteristics, yielding a nonlinear shrinkage estimator with efficiency advantages over the MLE. Our prior is mixture of Dirichlets, whereby species are stochastically partitioned into abundant and scarce classes, each with its own multivariate prior. Simulation studies reveal our estimator has lower integrated mean squared error (IMSE) than the MLE for the SAGE scenarios simulated, and yields relative abundance profiles closer in Euclidean distance to the truth for all samples simulated. We apply our method to a SAGE library of normal colon tissue, and discuss its implications for assessing differential expression. [source] Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implicationsCANCER SCIENCE, Issue 5 2004Wataru Yasui Gastric cancer is one of the most common human cancers and is the second most frequent cause of cancer-related death in the world. Serial analysis of gene expression (SAGE) is a powerful technique to allow genome-wide analysis of gene expression in a quantitative manner without prior knowledge of the gene sequences. SAGE on 5 samples of gastric cancer with different histology and clinical stages have created large SAGE libraries of gastric cancer that enable us to identify new cancer biomarkers. Commonly up-regulated genes in gastric cancer in comparison with normal gastric epithelia included CEACAM6, APOC1 and YF13H12. By comparing gene expression profiles of gastric cancers at early and advanced stages, several genes differentially expressed by tumor stage were also identified, including FUS, CDH17, COL1A1 and COL1A2, which should be novel genetic markers for high-grade malignancy. Regenerating gene type IV (REGIV) is one of the most up-regulated genes in a SAGE library of a scirrhous-type gastric cancer. In vitro studies using RegIV-transfected cells revealed that RegIV is secreted by cancer cells and inhibits apoptosis, suggesting that RegIV may serve as a novel biomarker and therapeutic target for gastric cancer. Production of RNA aptamers could be a useful approach to establish a detection system in blood. A custom-made array, named Ex-STO-MACHIP, consisting of 395 genes, including highly differentially expressed genes identified by our SAGE and other known genes related to carcinogenesis and chemosensitivity, is useful to study the molecular pathogenesis of gastric cancer and to obtain information about biological behavior and sensitivity to therapy in the clinical setting. Combined analyses of gene expression profile, genetic polymorphism and genetic instability will aid not only cancer detection, but also characterization of individual cancers and patients, leading to personalized medicine and cancer prevention. [source] Serial analysis of troponin I levels in patients with ischemic and nonischemic dilated cardiomyopathyCLINICAL CARDIOLOGY, Issue 5 2006Ulrich Nellessen M.D. Abstract Background: Ongoing myocardial cell damage forms the basis for progression of chronic heart failure. Evidence is accumulating that progressive loss of cardiac myocytes is associated with the release of cardiac troponin I (cTnI). Hypothesis: This study sought to determine whether levels of cTnI are of prognostic value for risk stratification of patients with chronic heart failure. Methods: Release of cTnI was measured by conventional enzyme immunoassay following serum ultrafiltration in 58 consecutive patients hospitalized for chronic heart failure and 31 healthy volunteers serving as control group. Determination of serum levels was performed every 2 weeks over a time interval of 3 months. According to the results of coronary angiography, patients were divided into Group D showing normal coronary arteries (n = 33, ejection fraction 27 ± 6.1%) and Group I showing severe coronary heart disease (n = 25, ejection fraction 28.8 ± 7.8%). Survival of patients was evaluated after a mean time interval of 3 years. Results: The mean cTnI serum level over all measurements was 0.66 ± 1.8 ng/ml in patients versus 0.11 ± 0.48 ng/ml in volunteers. At all six points of analysis, the mean cTnI serum level was significantly different (p < 0.001) between patients and volunteers. There was no significant difference between patients with and without coronary heart disease following hospital discharge, however, troponin release was significantly different between survivors and nonsurvivors (n = 27) (0.56 ng/ml vs. 0.84 ng/ml; p < 0.05). Conclusion: Permanent cTnI release is a common finding in patients with chronic heart failure and a strong prognosticator. In this setting, coronary morphology seems to play a minor role for disease progression. [source] Topical bovine thrombin: a 21-year review of topical bovine thrombin spontaneous case safety reports submitted to FDA's Adverse Event Reporting SystemPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 2 2010John A. Clark MD Abstract Purpose To review topical bovine thrombin spontaneous adverse event (AE) reports that were forwarded to the US Food and Drug Administration's (FDA) Adverse Event Reporting System (AERS) between January 1986 and December 2006. Methods Forty-one spontaneous AE reports were summarized for reported AE profile and chronological reporting patterns. Each AE report was adjudicated by a hematologist for the topical bovine thrombin product that was given and the AE(s) that were reported. AEs were grouped as allergic, coagulopathy/bleeding, and all other AEs combined. Grouped AE serial analyses were carried out using successive 3-year time increments between 1986 (the year an AE report was first noted for a bovine thrombin product) and 2006 (the first full year that was available at the time of initiation of the data summary). Main outcome measures The primary outcome measures were every 3-year trend lines for all-AE reports, all reporters, and topical bovine thrombin brand mentions for 2 AE groups of interest (allergic events and coagulopathy/bleeding events). Results The all-AE spontaneous reporter trend showed a downward appearance for AE reporting activity that started in 1995,1998 and continued through 2004,2006. The all-AE reports trend showed two potential safety signals that could be identified serially: (1) a prominent 1989,1991 peak that was attributable to allergic events (in particular, anaphylaxis), and (2) a small 1995,2000 broad peak that was attributable in part to coagulopathy/bleeding events. Allergic events were predominantly reported with products approved prior to 1995, were not temporally associated with prior medical literature case reports, and continued to be forwarded to the FDA at low levels up to the end of this study in 2006. Coagulopathy/bleeding events were reported only with products approved prior to 1995, were temporally associated with medical literature case reports, and were not forwarded to the FDA after 2000. Conclusions Overall, spontaneous AE reporting for topical bovine thrombin occurs at very low levels, and appears to have been decreasing since 1995. The serial reporting patterns for topical bovine thrombin are best explained as a strong safety signal for allergic events with ongoing, low level reporting, and a weak safety signal for coagulopathy/bleeding events that ceased on or before 2000. Although this descriptive trend analysis cannot measure associations or causation, the coagulopathy/bleeding signal may have been prompted by multiple, antecedent published case reports. The subsequent diminishment of signal attributed to thrombin likewise may coincide with lack of such reporting in larger follow-up clinical trials or, alternatively, in the introduction and growing market share of thrombin brands of greater purity. Currently marketed topical bovine thrombin formulations are rarely volunteered as possible causes of adverse events. Copyright © 2009 John Wiley & Sons, Ltd. [source] Immunocytochemical study of the expression of mesothelin in fine-needle aspiration biopsy specimens of pancreatic adenocarcinomaDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2007Amy C. Baruch M.D. Abstract Mesothelin is a potential marker of pancreatic adenocarcinoma that was recently identified by serial analysis of gene expression. We evaluated the sensitivity and specificity of mesothelin as a marker of pancreatic adenocarcinoma on destained Papanicolaou (Pap) smears and unstained cellblocks from 28 patients using a monoclonal antibody to mesothelin. Intensity and proportion of staining was semiquantitatively graded on a scale of 1,3, and as 0%, 1 to <10%, 10,50%, or >50%. Positive staining for mesothelin was seen in 64% of the direct smears and in 36% of cell block sections. Focal positivity for mesothelin was noted in benign pancreatic tissue in one of 10 cases. Staining was most often focal (<50% of cells) in both direct smears and cell block sections. The overall sensitivity and specificity of mesothelin as a marker for pancreatic adenocarcinoma were 68% and 90%, respectively. Sensitivity was higher in Pap smears than in cell block sections (64% versus 36%). The presence of occasional mesothelin expression in benign tissue, its very focal expression in malignant tissue may limit the utility of mesothelin as a marker of pancreatic adenocarcinomas in fine-needle aspiration (FNA) specimens. Diagn. Cytopathol. 2007;35:143,147. © 2007 Wiley-Liss, Inc. [source] High expression of B-cell receptor inducible gene BIC in all subtypes of Hodgkin lymphomaGENES, CHROMOSOMES AND CANCER, Issue 1 2003Anke van den Berg In a search for genes specifically expressed in Reed,Sternberg (RS) cells of Hodgkin lymphoma (HL), we applied the serial analysis of gene expression (SAGE) technique on the HL-derived cell line DEV. Genes highly expressed in DEV were subjected to an RT-PCR analysis to confirm the SAGE results. For one of the genes, a high expression was observed in DEV and other HL-derived cell lines but not in non-Hodgkin lymphoma (NHL),derived cell lines and normal controls, suggesting an HL-specific expression. This gene corresponds to the human BIC gene, a member of the noncoding mRNA-like molecules. RNA in situ hybridization (ISH) indicated an exclusive nucleolar localization of BIC transcripts in all RS cells in 91% of HL cases, including nodular lymphocyte predominance (NLP) HL and classical HL. Analyses of normal human tissues revealed BIC transcripts in only a small number of CD20-positive B-cells in lymph node and tonsil tissue, albeit at a much lower level compared to that of RS cells. BIC RT-PCR in the Burkitt lymphoma,derived cell line Ramos demonstrated a significant up-regulation upon cross-linking of the B-cell receptor (BcR). I,B,-mediated blocking of NF-,B translocation in Ramos did not effect the up-regulation of BIC expression upon BcR triggering, suggesting that activation of NF-,B is not involved in regulation of BIC expression. In summary, our data show that expression of BIC is specific for RS cells of HL. In normal tissue, BIC is expressed weakly in a minority of germinal center B cells. Expression of BIC can be modified/influenced by BcR triggering, indicating that BIC might play a role in the selection of B cells. © 2003 Wiley-Liss, Inc. [source] Different signaling pathways in the livers of patients with chronic hepatitis B or chronic hepatitis C,HEPATOLOGY, Issue 5 2006Masao Honda The clinical manifestations of chronic hepatitis B (CH-B) and chronic hepatitis C (CH-C) are different. We previously reported differences in the gene expression profiles of liver tissue infected with CH-B or CH-C; however, the signaling pathways underlying each condition have yet to be clarified. Using a newly constructed cDNA microarray consisting of 9614 clones selected from 256,550 tags of hepatic serial analysis of gene expression (SAGE) libraries, we compared the gene expression profiles of liver tissue from 24 CH-B patients with those of 23 CH-C patients. Laser capture microdissection was used to isolate hepatocytes from liver lobules and infiltrating lymphoid cells from the portal area, from 16 patients, for gene expression analysis. Furthermore, the comprehensive gene network was analyzed using SAGE libraries of CH-B and CH-C. Supervised and nonsupervised learning methods revealed that gene expression was correlated more with the infecting virus than any other clinical parameters such as histological stage and disease activity. Pro-apoptotic and DNA repair responses were predominant in CH-B with p53 and 14-3-3 interacting genes having an important role. In contrast, inflammatory and anti-apoptotic phenotypes were predominant in CH-C. These differences would evoke different oncogenic factors in CH-B and CH-C. In conclusion, we describe the different signaling pathways induced in the livers of patients with CH-B or CH-C. The results might be useful in guiding therapeutic strategies to prevent the development of hepatocellular carcinoma in cases of CH-B and CH-C. (HEPATOLOGY 2006;44:1122,1138.) [source] Anti-inflammatory effects in the skin of thymosin-,4 splice-variantsIMMUNOLOGY, Issue 1 2003Michael Girardi Summary The intraepithelial lymphocyte (IEL) network of T-cell receptor ,,+ (V,5+) dendritic epidermal T cells (DETC) in murine skin down-regulates cutaneous inflammation, although the mechanism is unknown. Thymosin-,4 (T,4), identified by serial analysis of gene expression as a predominant transcript in gut IEL, encodes both a ubiquitous actin-binding protein (UT,4) with demonstrated capacity to inhibit neutrophilic infiltration, and a splice-variant limited to lymphoid tissue (LT,4) with unknown bioactivity. Freshly isolated V,5+ DETCs expressed both forms, while only LT,4 was preferentially up-regulated after cellular activation in vitro. To compare the anti-inflammatory properties of LT,4 and UT,4 in the skin in vivo, the biological activities of synthesized polypeptides were assessed using three different strategies: neutrophil infiltration by footpad ,-carrageenan injection; irritant contact dermatitis to 12-O-tetradecanoylphorbol 13-acetate; and allergic contact dermatitis to 2,4-dinitrofluorobenzene. These studies clearly showed that the anti-inflammatory activities of LT,4 were broader and most often stronger than those of UT,4. Thus, the activation-responsive expression of the lymph-specific form of T,4 may be one mechanism by which DETC, and possibly other IELs, down-regulate local inflammation. [source] Microarray analysis of acaricide-inducible gene expression in the southern cattle tick, Rhipicephalus (Boophilus) microplusINSECT MOLECULAR BIOLOGY, Issue 6 2008L. Saldivar Abstract Acaricide-inducible differential gene expression was studied in larvae of Rhipicephalus (Boophilus) microplus using a microarray-based approach. The acaricides used were: coumaphos, permethrin, ivermectin, and amitraz. The microarrays contained over 13 000 probes, having been derived from a previously described R. microplus gene index (BmiGI Version 2; Wang et al., 2007). Relative quantitative reverse transcriptase-PCR, real time PCR, and serial analysis of gene expression data was used to verify microarray data. Among the differentially expressed genes with informative annotation were legumain, glutathione S-transferase, and a putative salivary gland-associated protein. [source] Life history of a mule (c. 160 AD) from the Roman fort Biriciana/Weißenburg (Upper Bavaria) as revealed by serial stable isotope analysis of dental tissuesINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 2 2010T. E. Berger Abstract The presence of the osseous remains of at least four mules in a garbage dump at the Roman fort of Biriciana near the town of Weißenburg, Upper Bavaria, dating to c. 160 AD, raised the question as to whether mule breeding was already performed to the north of the Alps during the Middle Roman Empire, or whether these animals still had to be imported from the Mediterranean. Serial analyses of the dental enamel and dentine of a lower fourth premolar and the surrounding alveolar bone of a mandible of a mule in terms of stable strontium isotopic ratios of the apatite, and stable carbon and oxygen isotope ratios of the structural carbonate, were carried out to test whether this individual moved long distances during its lifetime. Since isotopic ratios obtained by serial analysis can be correlated with consecutive ontogenetic stages, it can be assumed that this particular individual experienced significant changes in terms of diet and environmental parameters after its eighth year of life. These changes included a period of residence in a region of high altitude, most likely the Alps considering the location of the Roman fort where the mule was found. The isotopic data obtained do not contradict the assumption that this animal was bred and raised in northern Italy, to frequent later in its adult life the Alps and finally perish at Biriciana/Weißenburg. Copyright © 2008 John Wiley & Sons, Ltd. [source] Tumors Associated With Oncogenic Osteomalacia Express Genes Important in Bone and Mineral MetabolismJOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2002Suzanne M. Jan De Beur Abstract Oncogenic osteomalacia (OOM) is associated with primitive mesenchymal tumors that secrete phosphaturic factors resulting in low serum concentrations of phosphate and calcitriol, phosphaturia, and defective bone mineralization. To identify overexpressed genes in these tumors, we compared gene expression profiles of tumors resected from patients with OOM and histologically similar control tumors using serial analysis of gene expression (SAGE). Three hundred and sixty-four genes were expressed at least twofold greater in OOM tumors compared with control tumors. A subset of 67 highly expressed genes underwent validation with an extended set of OOM and control tumors using array analysis or reverse-transcription polymerase chain reaction (RT-PCR). Ten of these validated genes were consistently overexpressed in all OOM tumors relative to control tumors. Strikingly, genes with roles in bone matrix formation, mineral ion transport, and bone mineralization were highly expressed in the OOM tumors. [source] Comparative gene expression analysis reveals a characteristic molecular profile of the superior olivary complexTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 4 2006Hans Gerd Nothwang Abstract The superior olivary complex (SOC) is a very conspicuous structure in the mammalian auditory brainstem. It represents the first binaural processing center and is important for sound localization in the azimuth and in feedback regulation of cochlear function. In order to define molecular determinants of the SOC, which are of potential functional relevance, we have performed a comprehensive analysis of its transcriptome by serial analysis of gene expression in adult rats. Here, we performed a detailed analysis of the SOC's gene expression profile compared to that of two other neural tissues, the striatum and the hippocampus, and with extraocular muscle tissue. This tested the hypothesis that SOC-specific or significantly upregulated transcripts provide candidates for the specific function of auditory neurons. Thirty-three genes were significantly upregulated in the SOC when compared to the two other neural tissues. Thirteen encoded proteins involved in neurotransmission, including action potential propagation, exocytosis, and myelination; five genes are important for the energy metabolism, and five transcripts are unknown or poorly characterized and have yet to be described in the nervous system. The comparison of functional gene classes indicates that the SOC has the highest energy demand of the three neural tissues, yet protein turnover is apparently not increased. This suggests a high energy demand for fueling auditory neurotransmission. Such a demand may have implications on auditory-specific tasks and relate to central auditory processing disorders. Ultimately, these data provide new avenues to foster investigations of auditory function and to advance molecular physiology in the central auditory system. Anat Rec Part A, 2006. © 2006 Wiley-Liss, Inc. [source] Prostate-Specific genes and their regulation by dihydrotestosteroneTHE PROSTATE, Issue 3 2008Ma Ci Abstract BACKGROUND Prostate is a well-known androgen-dependent tissue. METHODS By sequencing 4,294,186 serial analysis of gene expression (SAGE) tags, we have investigated the transcriptomes of normal mouse prostate, liver, testis, lung, brain, femur, skin, adipose tissue, skeletal muscle, vagina, ovary, mammary gland, and uterus in order to identify the most abundant and tissue-specific transcripts in the prostate, as well as to target the androgen responsive transcripts specifically regulated in the prostate. Small interference RNA (siRNA) in LNCaP cells was applied to validate the roles of prostate-specific/enriched ARGs in the growth of human prostate cancer cells. RESULTS The most abundant transcripts were involved in prostatic secretion, energy metabolism and immunity. Previously well-known prostate-specific transcripts, including many transcripts involved in prostatic secretion, polyamine biosynthesis and transport, and immunity were specific/enriched in the prostate. Only 22 transcripts among 114 androgen-regulated genes (ARGs) in the mouse prostate were modulated by dihydrotestosterone (DHT) in two or more tissues. The siRNA results showed that inhibition of HSPA5 and MAT2A gene expression repressed growth of human cancer LNCaP cells. Conclusions The current study globally assessed the transcriptome of the prostate and revealed the most abundant and tissue-specific transcripts which are responsible for the unique functions of this organ. These prostate-specific ARGs might be used as targets to develop safe and effective gene-based therapy for the prevention and treatment of prostate cancer. Prostate 68: 241,254, 2008. © 2007 Wiley-Liss, Inc. [source] Differentially expressed genes during bovine intramuscular adipocyte differentiation profiled by serial analysis of gene expressionANIMAL GENETICS, Issue 4 2010Y. Mizoguchi Summary Beef marbling or intramuscular fat deposition is an economically important carcass trait in Japanese Black cattle. To investigate genes involved in intramuscular adipogenesis, differential gene expression during adipogenesis in a clonal bovine intramuscular preadipocyte (BIP) cell line was profiled with serial analysis of gene expression (SAGE). We sequenced 75 283 tags for the proliferation phase (day 0) and 81 878 tags for the differentiation phase (4 days after adipogenic stimulation: day 4). A comparison of the unique SAGE tag frequencies between the day 0- and day 4-libraries revealed that 878 (2.8%) of the 30 989 unique putative transcripts were expressed at significantly different levels (P < 0.05); 401 tags (1.4%) were up-regulated and 477 tags (1.2%) were down-regulated in the day 4-library relative to the day 0-library. We confirmed up-regulation of 10 tags of the genes that were up-regulated in the previous subtraction cloning studies in BIP cells [Animal Science Journal, 76 (2005) 479]. Of the 878 differentially expressed tags, 377 were identified in the bovine RefSeq library and 356 were assigned a bovine draft genomic sequence. Fifteen tags were mapped in previously detected beef marbling quantitative trait loci (QTL) regions [Mammalian Genome, 18 (2007) 125]. These genes may be involved in the adipogenic processes of beef marbling. [source] Pilot Study: Noninvasive Monitoring of Oral Flecainide's Effects on Atrial Electrophysiology during Persistent Human Atrial Fibrillation Using the Surface ElectrocardiogramANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 2 2005Daniela Husser M.D. Background: The relation between flecainide's plasma level and its influence on human atrial electrophysiology during acute and maintenance therapy of atrial fibrillation (AF) is unknown. Therefore, this study determined flecainide plasma levels and atrial fibrillatory rate obtained from the surface ECG during initiation and early maintenance of oral flecainide in patients with persistent lone AF and assessed their relationship. Methods and Results: In 10 patients (5 males, mean age 63 ± 14 years, left atrial diameter 46 ± 3 mm) with persistent lone AF, flecainide was administered as a single oral bolus (day 1) followed by 200,400 mg/day (days 2,5). The initial 300 mg flecainide bolus resulted in therapeutic plasma levels in all patients (range 288,629 ng/ml) with no side effects. Flecainide plasma levels increased on day 3 and remained stable thereafter. Day 5 plasma levels were lower (508 ± 135 vs 974 ± 276 ng/ml, P = 0.009) in patients with daily mean flecainide doses of 200 mg compared to patients with higher maintenance doses. Fibrillatory rate obtained from the surface electrocardiogram measuring 378 ± 17 fpm at baseline was reduced to 270 ± 18 fpm (P < 0.001) after the flecainide bolus but remained stable thereafter. Fibrillatory rate reduction was independent of flecainide plasma levels or clinical variables. Conclusion: A 300 mg oral flecainide bolus is associated with electrophysiologic effects that are not increased during early maintenance therapy in persistent human lone AF. In contrast to drug plasma levels, serial analysis of fibrillatory rate allows monitoring of individual drug effects on atrial electrophysiology. [source] The effect of oestrogen and testosterone on the urethral seam of the developing male mouse genital tubercleBJU INTERNATIONAL, Issue 9 2003S. Yucel OBJECTIVES To describe the effects of exogenous oestrogens and androgens on urethral formation in the mouse, as the development of the mouse and human urethra have significant similarities, and understanding normal male urethral development may help to identify the causes of abnormal development, e.g. hypospadias. MATERIALS AND METHODS Timed-pregnant C57/6 mice were exposed to synthetic oestrogens and androgens. The morphology of the genital tubercles was examined histologically and with three-dimensional computer reconstruction. Specific attention was focused on the developing urethral seam. RESULTS Microscopic serial analysis confirmed the presence of an arrest in seam formation in about half of oestrogen-treated male fetuses. In contrast, there was acceleration of urethral fold fusion and a longer urethral tube in those treated with androgens. Oestrogen-treated fetuses had a thin periurethral spongiosa, in contrast to androgen-treated fetuses which developed a thicker periurethral spongiosa. The effect of oestrogens on seam area formation did not depend on the dose, but in contrast, in the androgen-treated fetuses it was. CONCLUSION Oestrogens and androgens have a direct effect on the fusion of the urethral fold that leads to seam formation. Normal urethral development depends on the delicate balance of these complementary hormones. [source] Overexpression of synuclein-, in pancreatic adenocarcinomaCANCER, Issue 1 2004Zhongkui Li Ph.D. Abstract BACKGROUND Currently, pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Despite the advances in pancreatic carcinoma research, patients with this devastating disease have a very poor prognosis. To identify the gene expression profile of pancreatic carcinoma, an important step in the process of developing new diagnostic and therapeutic strategies, the authors investigated the alteration of gene expression in this disease. METHODS The authors analyzed a public serial analysis of gene expression (SAGE) database and examined in greater detail the expression of synuclein-, mRNA in several pancreatic carcinoma cell lines and tumor tissue samples by reverse transcriptase,polymerase chain reaction (RT-PCR) analysis and Northern blot analysis. The expression of synuclein-, protein was investigated further by immunohistochemical and Western blot analyses using tumor cell lines, tumor tissue, and serum samples. RESULTS Synuclein-, mRNA was overexpressed in 11 of 12 pancreatic carcinoma cell lines, including AsPc-1, MDAPanc28, Capan-1, Capan-2, PANC-1, HS766T, MDAPanc3, MDAPanc48, Colo357FG, MiaPaCa2, CFPac1, and BxPc3. The expression of synuclein-, protein was detectable in 8 of 12 pancreatic carcinoma cell lines (67%) and in 22 of 32 pancreatic tumor tissue samples (69%) by Western blot analysis. On immunohistochemical staining, synuclein-, protein was present in 61% of the tumor tissue samples examined from patients with Stage I and II pancreatic carcinoma. The overexpression of synuclein-, is correlated with perineural and lymph node invasion. Synuclein-, protein also was detectable by Western blot in serum samples from 21 of 56 patients (38%) with pancreatic carcinoma. CONCLUSIONS Synuclein-,, which initially was described as a breast carcinoma,specific gene involved in invasion, metastasis, and chemotherapy resistance, was frequently overexpressed in pancreatic carcinoma. Overexpression of synuclein-, may play a role in pancreatic carcinoma invasion. Further studies will be necessary to determine the role of synuclein-, in pancreatic carcinoma. Cancer 2004. © 2004 American Cancer Society. [source] Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implicationsCANCER SCIENCE, Issue 5 2004Wataru Yasui Gastric cancer is one of the most common human cancers and is the second most frequent cause of cancer-related death in the world. Serial analysis of gene expression (SAGE) is a powerful technique to allow genome-wide analysis of gene expression in a quantitative manner without prior knowledge of the gene sequences. SAGE on 5 samples of gastric cancer with different histology and clinical stages have created large SAGE libraries of gastric cancer that enable us to identify new cancer biomarkers. Commonly up-regulated genes in gastric cancer in comparison with normal gastric epithelia included CEACAM6, APOC1 and YF13H12. By comparing gene expression profiles of gastric cancers at early and advanced stages, several genes differentially expressed by tumor stage were also identified, including FUS, CDH17, COL1A1 and COL1A2, which should be novel genetic markers for high-grade malignancy. Regenerating gene type IV (REGIV) is one of the most up-regulated genes in a SAGE library of a scirrhous-type gastric cancer. In vitro studies using RegIV-transfected cells revealed that RegIV is secreted by cancer cells and inhibits apoptosis, suggesting that RegIV may serve as a novel biomarker and therapeutic target for gastric cancer. Production of RNA aptamers could be a useful approach to establish a detection system in blood. A custom-made array, named Ex-STO-MACHIP, consisting of 395 genes, including highly differentially expressed genes identified by our SAGE and other known genes related to carcinogenesis and chemosensitivity, is useful to study the molecular pathogenesis of gastric cancer and to obtain information about biological behavior and sensitivity to therapy in the clinical setting. Combined analyses of gene expression profile, genetic polymorphism and genetic instability will aid not only cancer detection, but also characterization of individual cancers and patients, leading to personalized medicine and cancer prevention. [source] | |||||||||||||||||||||||||||||||