tbuckley/cabot-search huggingface dataset:
Oncogenomic transcriptional hotspots in Barretts adenocarcinomas
Authors: Mohammad Razvi, Altaf Dar, Mary Washington, Wael El-Rifai
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2981 

Serial analysis of gene expression (SAGE) provides quantitative and comprehensive expression profiling in a given cell population. In our efforts to define gene expression alterations in Barrett’s related adenocarcinomas and to look for correlations in chromosomal location, we produced eight SAGE libraries from dissected neoplastic and normal epithelia. Sequence analyses of 20,000 clones produced a total of 457,894 expressed tags with 67,200 unique tags. These tags represent 16,040 known gene symbols. Comparison of normal and tumor library results demonstrated an up-regulation of 242 genes and a down-regulation of 153 genes (two fold change, p<0.05). Ninety-three genes showed five fold or greater change in expression (p≤0.01) in at least two tumor samples as compared to all four normal libraries. In order to identify potential oncogenomic transcriptional hot spots in the Barrett’s genome, we have characterized the cytogenetic location of all altered genes. Interestingly, we found that the distribution of these altered genes was not uniform across the human genome. Overexpressed genes tended to cluster in well defined hotspots located in certain chromosomes. We also found that the number of genetic changes did not correlate with chromosome size. Chromosome 19 had twenty-six overexpressed genes of which eighteen mapped to 19q13. Similarly, thirty-five genes mapped to chromosome 1 of which thirteen mapped to 1q21. Using Gene Ontology, We then assigned each gene to a functional group and found several groups that we believe to be highly relevant to cancer. Examples of the more interesting functional groups are cell cycle regulation, DNA binding and regulation, and cell signaling. SAGE results of five representative genes were then validated using quantitative real time RT PCR on 31 primary tumor samples and 23 normal samples. The results confirmed the over-expression of ANPEP, ECGF1, PP1201, EIF5A1 , and the down-regulation of GKN in primary tumor samples as compared to normal tissues. Interestingly, the expression of GKN1 was absent in normal esophageal mucosa whereas Barrett’s esophagus epithelia had high expression levels of GKN1 that was lost in matching tumor samples. In addition, we performed immunohistochemistry analysis for ANPEP on a tumor tissue array that contained 72 samples. The results demonstrate a high expression level of ANPEP in upper gastrointestinal adenocarcinomas. ANPEP is a secreted protein that may have diagnostic or prognostic significance for Barrett’s progression. Using SAGE analysis we have been able to identify and further validate oncogenomic transcriptional hotspots containing multiple genes of functional importance that show changes in expression and may have clinical significance.
Abstract 13768: Intracoronary Infusion of Bone Marrow-Derived Mesenchymal Stromal Cells Expressing Heme Oxygenase-1 to Prevent Reperfusion Injury in Porcine Model of Myocardial Infarction
Authors: Wojciech Wojakowski, Michal Tendera, Wieslaw Cybulski, Ewa K Zuba-Surma, Krzysztof Szade, Urszula Florczyk, Magdalena Kozakowska, Agnieszka Szymula, ukasz Krzych, Urszula Paslawska, Robert Paslawski, Krzysztof Milewski, Piotr P Buszman, Adrian Janiszewski, Piotr Dziegiel, Pawel E Buszman, Alicja Joozkowicz, Joozef Dulak
Journal: Circulation (2011)

Combination of mesenchymal stromal cells (MSC) with antioxidative, antiapoptotic and proangiogenic enzyme heme oxygenase-1 (HO-1) is a novel approach for prevention of reperfusion injury in acute M...
Oral administration of gentamicin for prophylaxis of KPC-producing Klebsiella pneumoniae gut colonization in patients treated with a novel parenchymal-sparing liver surgery: the GEN Gut study
Authors: Carlo Tascini, Lucio Urbani, Francesco Sbrana, Francesco Forfori, Gabriella Licitra, Chiara Leoni, Riccardo Balestri, Elisabetta Rossi, Simona Fortunato, Alessandro Leonildi, Marco Puccini, Antonello Di Paolo, Andrea Ripoli, Piero Colombatto, Francesco Menichetti, Piero Buccianti
Journal: Intensive Care Medicine (2015)
Lithium treatment of conduct disorders in adolescents
Authors: A Rifkin, B Karajgi, R Dicker, E Perl, V Boppana, N Hasan, S Pollack
Journal: American Journal of Psychiatry (1997)

The authors examined the efficacy of lithium carbonate for treating conduct disorder in adolescents.The subjects were 33 inpatients aged 12-17 years. Lithium or placebo was administered in a double-blind fashion for 2 weeks.On several measures of clinical change the groups showed no significant differences. Of the patients who completed the study, 8.3% of those receiving placebo (one of 12) versus 21.4% (three of 14) of those receiving lithium were considered responders.Lithium does not appear beneficial for this indication.
Abstract #2310: Differential gene expression profiles as markers of radiosensitivity in esophageal cancer
Authors: Niamh Lynam-Lennon, Stephen Maher, John Reynolds
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Introduction: The current standard of care for esophageal cancer is a multi-modal approach, whereby patients receive neoadjuvant radiochemotherapy followed by surgery. However, only one third of patients have a good response to therapy. The identification of a molecular signature which could predict patient response would be of substantial clinical benefit. This study aims to identify genes involved in determining radiosensitivity in an esophageal isogenic cell line model of radioresistance. Methods: KYSE-410 human esophageal squamous cell carcinoma cells were irradiated with fractionated doses of 2 Gy X-ray radiation every 10 days until a radioresistant subline was established. Radioresistance was assessed by clonogenic assay and crystal violet staining. Differential gene expression in response to radiation was screened using Cancer Pathway Finder Arrays. Validation of differential gene expression was performed by reverse-transcriptase PCR. Cell cycle analysis was carried out using propidium iodide staining and flow cytometry. Results: Exposure of KYSE-410 cells to fractionated doses of radiation resulted in the generation of a radioresistant clone. The cell cycle distribution of both parent and resistant clone appear to be similar. MMP-1, S100A4, IFNB1 and DR3 were demonstrated to be differentially regulated between the parent and radioresistant clone both at the basal level and in response to radiation. All four genes were upregulated in the radioresistant clone at the basal level. Stimulation of the parent with 2-Gy X-ray radiation, typically resulted in a bi-phasic induction of expression of these genes, whilst gene expression in response to radiation remained largely unchanged or downregulated in radioresistant cells. Conclusion: Through the generation of a radioresistant subline that differs from the parent only in terms of its radiosensitivity, we could identify genes truly involved in determining radiosensitivity. The position in the cell cycle affects radiosensitivity, with cells in G2/M phase being most sensitive to radiation. Cell cycle analysis indicated that the cell cycle distributions of both KYSE-410 P and KYSE-410-R15 were similar, which implies that changes in cell cycle are not responsible for the altered response to radiation. Four genes; DR3, MMP-1, IFNB1 and S100A4 were demonstrated to be differentially expressed at the basal level, and were demonstrated to be radiation-induced, indicating a role in determining response. The identification of genes involved in radio-response may allow us to identify those patients most likely to benefit from neoadjuvant radiochemotherapy, as well as expanding our understanding of the complex biological mechanisms underlying the response to radiation.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2310.
Fetal-to-maternal signaling to initiate parturition
Authors: Erin L. Reinl, Sarah K. England
Journal: Journal of Clinical Investigation (2015)

Multiple processes are capable of activating the onset of parturition; however, the specific contributions of the mother and the fetus to this process are not fully understood. In this issue of the JCI, Gao and colleagues present evidence that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) regulate surfactant protein-A (SP-A) and platelet-activating factor (PAF) expression, which increases in the developing fetal lung. WT dams crossed with males deficient for both SRC-1 and SRC-2 had suppressed myometrial inflammation, increased serum progesterone, and delayed parturition, which could be reconciled by injection of either SP-A or PAF into the amnion. Together, the results of this study demonstrate that the fetal lungs produce signals to initiate labor in the mouse. This work underscores the importance of the fetus as a contributor to the onset of murine, and potentially human, parturition.
Abstract 824: The Role of the Small GTPase Rap1 for Angiogenesis
Authors: Guillaume Carmona, Emmanouil Chavakis
Journal: Circulation (2006)

The molecular mechanisms regulating angiogenesis are not completely understood. Integrins are critical mediators of angiogenesis. Recent evidence suggests that Rap1, a small GTPase of the Ras-family, is an important regulator of integrin activity and junctional adhesion in many cellular systems. However, the role of Rap1 genes in angiogenesis is unclear. In the present study, we investigated the role of Rap1a and Rap1b for angiogenesis. Human umbilical vein endothelial cells (HUVEC) express mRNA for Rap1a and Rap1b, as assessed by RT-PCR. In order to determine the relevance of Rap1 activity for angiogenesis, we overexpressed RapGAP1, a GTPase activating protein, which specifically inhibits the activity of both Rap1a and Rap1b. Overexpression of RapGAP1 led to a significant inhibition of angiogenic sprouting of HUVEC under basal conditions and after bFGF stimulation by 44 ± 5 % as assessed by a 3-dimensional spheroidal endothelial cell culture system. In addition, overexpression of RapGAP1 significantly blocked tube formation in a matrigel assay (by 62 ± 12 %) and the HUVEC migration and adhesion on fibronectin and collagen. In order to separately investigate the role of Rap1a and Rap1b genes for angiogenesis, we performed gene silencing with siRNA. Silencing of either Rap1a or Rap1b gene significantly and additively blocked the sprouting of HUVEC under basal and bFGF-stimulated conditions (Rap1a-siRNA: 55 ± 5 %, Rap1b-siRNA: 61 ± 9 % and Rap1a+Rap1b siRNA: 73 ± 5% inhibition). Moreover, silencing of either Rap1a or Rap1b or both significantly reduced HUVEC migration and adhesion, but had no effect on proliferation as assessed by BrdU-staining. These data reveal for the first time that Rap1a and Rap1b are essential mediators of angiogenesis by mediating endothelial cell migration and adhesion on extracellular matrix proteins. The  in-vivo  role of Rap1a is currently being investigated in Rap1a-deficient mice. Understanding of the molecular mechanisms of angiogenesis is crucial for the development of new therapeutic strategies in order to increase neovascularization in patients with ischemic disorders or to reduce angiogenesis in patients with tumor diseases.
Team for the Assessment of Psychiatric Services (TAPS) Project 33: prospective follow-up study of long-stay patients discharged from two psychiatric hospitals
Authors: J Leff, N Trieman, C Gooch
Journal: American Journal of Psychiatry (1996)

The purpose of this study was to evaluate the policy of closing psychiatric hospitals and replacing their functions with community-based services.All long-stay nondemented patients in two U.K. hospitals scheduled for closure were assessed with a series of schedules. All patients in one hospital and a proportion of those in the other hospital were reassessed 1 year after discharge to community facilities.Of the 737 patients discharged from the two hospitals, 24 died before follow-up, two by suicide. Follow-up was successful for 94.6% of the survivors. Only seven patients were lost to follow-up and are presumed to have become homeless. Only two patients went to prison, one briefly. There was very little change in patients' psychiatric symptoms or social behavior problems. The community homes provided a much less restrictive environment than the hospital wards. Discharged patients were very appreciative of their increased freedom, and over 80% wished to stay in their community homes. There was an increase in the proportion of patients with incontinence and immobility. The patients' social lives were enriched by an increase in friends, and some made contact with neighbors and others in the community. However, there was a decrease in contact with relatives following discharge.When the capital and revenue resources of a psychiatric hospital are reinvested in community services, based on staffed houses, there are few problems with crime or homelessness. With such well-resourced services, the benefits greatly outweigh the disadvantages for both old and new long-stay patients.
Whole-genome sequencing reveals oncogenic mutations in mycosis fungoides
Authors: Laura Y. McGirt, Peilin Jia, Devin A. Baerenwald, Robert J. Duszynski, Kimberly B. Dahlman, John A. Zic, Jeffrey P. Zwerner, Donald Hucks, Utpal Dave, Zhongming Zhao, Christine M. Eischen
Journal: Blood (2015)
An international multi-centre, randomized, open-label, phase III trial comparing rituximab added to CVP chemotherapy to CVP chemotherapy alone in untreated stage III/IV follicular non-Hodgkins lymphoma.
Authors: R Marcus, K Imrie, A Belch, D Cunningham, E Flores, J Catalano, P Solal-Celigny, Fritz Offner, J Walewski, J Raposo, A Jack, P Smith
Journal: Blood (2003)
Lithium and tricyclic augmentation of fluoxetine treatment for resistant major depression: a double-blind, controlled study
Authors: M Fava, J F Rosenbaum, P J McGrath, J W Stewart, J D Amsterdam, F M Quitkin
Journal: American Journal of Psychiatry (1994)

Forty-one patients who had failed to respond to 8 weeks of treatment with 20 mg of fluoxetine were randomly assigned to one of three treatments for 4 weeks: 40-60 mg/day of fluoxetine, 20 mg/day of fluoxetine plus 25-50 mg/day of desipramine, and 20 mg/day of fluoxetine plus 300-600 mg/day of lithium. Patients treated with high-dose fluoxetine (N = 15) did significantly better than patients treated with fluoxetine plus lithium (N = 14) and those treated with fluoxetine plus desipramine (N = 12). High-dose fluoxetine was the most effective treatment among partial responders to previous treatment, but high-dose fluoxetine and fluoxetine plus lithium were the most effective treatments among nonresponders.
Chronic nasal inflammation in asthmatic patients with eosinophilic granulomatosis with polyangitis (EGPA)
Authors: Manuela Latorre, Veronica Seccia, Federica Novelli, Chiara Baldini, Elena Bacci, Maria Laura Bartoli, Silvana Cianchetti, Federico Dente, Antonella Di Franco, Pier Luigi Paggiaro
Journal: European Respiratory Journal (2014)

Background: nasal disease is a condition that may negative influence the asthma control and quality of life of EGPA patients  Aim:to define the different nasal diseases in EGPA patients and their impact on asthma control and quality of life  Methods:Were enrolled 37 EGPA patients and assessed:blood/sputum eosinophilia, exhaled/nasal nitric oxide(FeNO-NNO),nasal cytology, lung function, bronchial hyperreactivity and ACT test.Nasal polyps were graded according to the HOX endoscopy score.The short form (SF)-36,the Sino-Nasal Outcome Test (SNOT22) and the Asthma Quality of Life Questionnaire (AQLQ)were used  Results:the nasal disease preceded the EGPA onset of 17 yrs in mean;chronic rhinosinusitis with nasal polyps(CRSwNP)was identified in 54%, chronic rhinosinusitis in 22%, allergic rhinitis in 6% and non-allergic rhinitis with eosinophilia and neutrophilia in the 9 and6% of the cases. One patient hadn9t a nasal disease.The nasal cytology was positive for eosinophils in the 67% of the patients.The majority of patients showed a moderate/severe asthma partially/poorly controlled. No correlation was found among CRSwP and blood or sputum eosinophilia,FeNO,NNO, lung function and ACT.  SNOT22 was significantly correlated with SF-36 questionnaire(p  Conclusions:nasal disease represents the initial feature of EGPA, and may have a great impact on the patients quality of life and the asthma control.
Abstract 14498: Allopurinol Reduces Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiorenal Patients
Authors: Michelle P Kao, Donald S Ang, Chim C Lang, Allan D Struthers
Journal: Circulation (2010)

Introduction: Left ventricular hypertrophy (LVH) and vascular dysfunction are key pathophysiological processes that lead to cardiovascular (CV) events in patients with chronic kidney disease (CKD). As oxidative stress is thought to contribute to both LVH and endothelial dysfunction in CKD, we hypothesized that allopurinol might regress left ventricular (LV) mass and improve endothelial dysfunction and arterial stiffness in CKD patients. Methods: A randomised, double-blind, placebo-controlled, parallel study was conducted in patients with CKD stage 3 and LVH. Subjects received 300mg/day Allopurinol or placebo for 9 months. Cardiac magnetic resonance (CMR) was performed to measure LV mass index (LVMI). Endothelial function was assessed by flow-mediated dilatation (FMD) of the brachial artery, while central arterial stiffness was assessed by pulse wave analysis (PWA) and pulse wave velocity (PWV). Results: 53 patients completed the study (27 active, 26 placebo). Allopurinol significantly reduced LVH [ΔLVMI: ...
Screening of p53 regulated genes by cDNA microarray and analysis of its expression in cancer tissue
Authors: Koichi Matsuda, Chizu Tanikawa, Tomohide Kidokoro, Yusuke Nakamura
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3349 

Although a number of p53-targets have been reported so far, the physiological function of these genes in p53-dependent tumor suppression is still largely unknown. Our previous cDNA microarray analysis revealed that more than 100 genes were up-regulated or down-regulated by introduction of ectopic expression of p53. To clarify the physiological functions of these p53-regulated genes, we examined the expressions of these genes in more than 1000 cancer tissues using gene expression database that was constructed by means of cDNA microarray system established in our laboratory. As p53 gene product is inactivated in the majority of the cancer tissues due to its genetic, epigenetic or post-translational change, p53-target genes involved in tumor suppression are possibly down-regulated in cancer cells. In our microarray analysis, most of p53-target genes revealed no significant change in their transcriptional levels. However, we identified three genes whose expression was up-regulated by introduction of p53 and was down-regulated in many cancer tissues. Interestingly, four genes whose expression was repressed by p53 and was overexpressed in cancer cells were also identified. The expression levels of these genes were increased or decreased by DNA damage in a p53-dependent manner, respectively. Our findings suggest that these subset of p53-target genes play an important role in human carcinogenesis.
Repetitive Artery-to-Artery Embolism Caused by Dynamic Movement of the Internal Carotid Artery and Mechanical Stimulation by the Hyoid Bone
Authors: Keisuke Tokunaga, Toshiyuki Uehara, Hideki Kanamaru, Hiroharu Kataoka, Kozue Saito, Hatsue Ishibashi-Ueda, Ryogo Shobatake, Yoshifumi Yamamoto, Kazunori Toyoda
Journal: Circulation (2015)
Reply
Authors: Jasmohan S. Bajaj, Huiping Zhou, Dae Joong Kang, Phillip B. Hylemon
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. Reply: We would like to thank Åberg et al. for their interest in our article. They raise excellent points regarding the oral‐hepatic‐gut axis that deserve further investigation. As part of our study, we indeed excluded patients with periodontitis precisely owing to the excellent points raised, which lays out a path for periodontitis leading independently to inflammation and liver injury in some models.1 This was performed by means of an oral health examination as part of standard of care given that a majority of these subjects were being considered for liver transplant.3 However, the focus of our study was on cirrhosis‐related, rather than periodontal, issues. Therefore, our findings of altered salivary inflammation and local defenses with microbial function overexpressing endotoxin‐related genes may be an important complement to previous work that demonstrates systemic inflammation as a mechanism for progression in cirrhosis.4 Key questions to be answered by future research should include: (1) Is cirrhosis causing a significant defect in host immunity allowing changes in both the gut and oral microbiota? and (2) What is the relative contribution to systemic inflammation caused by changes in the oral versus gut microbiota? Therefore, evidence is slowly gathering that a newer front in the oral cavity may be opening up in the management of cirrhosis, and the study of the oral‐hepatic‐gut axis is a relevant pathophysiological goal.
Familial IgA Nephropathy
Authors: F Scolari
Journal: New England Journal of Medicine (1985)

To date, more than 90 families with multiple members with IgA nephropathy have been reported. The case for genetic predisposition as a cause of familial clustering of IgA nephropathy is supported by several factors, including variable time points in the onset of the disease in relatives with IgA nephropathy; the presence of abnormalities of IgA production in both affected and unaffected family members; the clustering of the birthplaces of ancestors of large pedigrees containing multiple affected members with IgA nephropathy, which suggests the existence of a "founder effect". Immunogenetic studies does not conclusively indicate that HLA is involved in the pathogenesis of IgA nephropathy. The specific mode of inheritance of familial IgA nephropathy is difficult to establish with certainty. IgA nephropathy may be a single gene trait with incomplete penetrance. Alternatively, a multifactorial genetic disease could account for the increased prevalence of the disorder among relatives of affected individuals. Clinicians must become aware that IgA nephropathy may aggregate within families in a substantial number of cases. The availability of multiplex families offers an ideal opportunity to design a molecular genetics approach to map the gene(s) or pathway(s) responsible for the development of IgA nephropathy.
Determining Cell-Of-Origin Subtypes In Diffuse Large B-Cell Lymphoma Using Gene Expression Profiling On Formalin-Fixed Paraffin-Embedded Tissue – An L.L.M.P.P. Project
Authors: David W. Scott, George W. Wright, Mickey Williams, Jason Lih, William Walsh, Elaine S. Jaffe, Andreas Rosenwald, Elias Campo, Wing C. Chan, Joseph M. Connors, Erlend B. Smeland, Anja Mottok, Rita M. Braziel, German Ott, Jan Delabie, Raymond R. Tubbs, James R. Cook, Dennis D Weisenburger, Timothy C. Greiner, Betty J. Glinsmann-Gibson, Kai Fu, Louis M. Staudt, Randy D. Gascoyne, Lisa M. Rimsza
Journal: Blood (2013)
Abstract 12562: Performance Analysis of EUROSCORE 2 as Compared to Logistic EuroSCORE and STS Scores for Predicting 30-day Mortality after Transcatheter Aortic Valve Replacement
Authors: Eric Durand, Bogdan Borz, Matthieu Godin, Christophe Tron, Pierre-Yves Litzler, Jean-Paul Bessou, Jean-Nicolas Dacher, Fabrice Bauer, Alain Cribier, Helene Eltchaninoff
Journal: Circulation (2012)