tbuckley/cabot-search huggingface dataset:
Telomere Maintenance in Laser Capture Microdissection–Purified Barrett's Adenocarcinoma Cells and Effect of Telomerase Inhibition <i>In vivo</i>
Authors: Masood A. Shammas, Aamer Qazi, Ramesh B. Batchu, Robert C. Bertheau, Jason Y.Y. Wong, Manjula Y. Rao, Madhu Prasad, Diptiman Chanda, Selvarangan Ponnazhagan, Kenneth C. Anderson, Christopher P. Steffes, Nikhil C. Munshi, Immaculata De Vivo, David G. Beer, Sergei Gryaznov, Donald W. Weaver, Raj K. Goyal
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The aims of this study were to investigate telomere function in normal and Barrett's esophageal adenocarcinoma (BEAC) cells purified by laser capture microdissection and to evaluate the effect of telomerase inhibition in cancer cells in vitro and in vivo. Experimental Design: Epithelial cells were purified from surgically resected esophagi. Telomerase activity was measured by modified telomeric repeat amplification protocol and telomere length was determined by real-time PCR assay. To evaluate the effect of telomerase inhibition, adenocarcinoma cell lines were continuously treated with a specific telomerase inhibitor (GRN163L) and live cell number was determined weekly. Apoptosis was evaluated by Annexin labeling and senescence by β-galactosidase staining. For in vivo studies, severe combined immunodeficient mice were s.c. inoculated with adenocarcinoma cells and following appearance of palpable tumors, injected i.p. with saline or GRN163L. Results: Telomerase activity was significantly elevated whereas telomeres were shorter in BEAC cells relative to normal esophageal epithelial cells. The treatment of adenocarcinoma cells with telomerase inhibitor, GRN163L, led to loss of telomerase activity, reduction in telomere length, and growth arrest through induction of both the senescence and apoptosis. GRN163L-induced cell death could also be expedited by addition of the chemotherapeutic agents doxorubicin and ritonavir. Finally, the treatment with GRN163L led to a significant reduction in tumor volume in a subcutaneous tumor model. Conclusions: We show that telomerase activity is significantly elevated whereas telomeres are shorter in BEAC and suppression of telomerase inhibits proliferation of adenocarcinoma cells both in vitro and in vivo.
Velocardiofacial Syndrome: Are Structural Changes in the Temporal and Mesial Temporal Regions Related to Schizophrenia?
Authors: Stephan Eliez, Christine M. Blasey, Eric J. Schmitt, Christopher D. White, David Hu, Allan L. Reiss
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Velocardiofacial syndrome results from a microdeletion on chromosome 22 (22q11.2). Clinical studies indicate that more than 30% of children with the syndrome will develop schizophrenia. The authors sought to determine whether neuroanatomical features in velocardiofacial syndrome are similar to those reported in the literature on schizophrenia by measuring the volumes of the temporal lobe, superior temporal gyrus, and mesial temporal structures in children and adolescents with velocardiofacial syndrome. METHOD: Twenty-three children and adolescents with velocardiofacial syndrome and 23 comparison subjects, individually matched for age and gender, received brain magnetic resonance imaging (MRI) scans. Analysis of covariance models were used to compare regional brain volumes. Correlations between residualized brain volumes and age were standardized and compared with the Fisher r-to-z transformation. RESULTS: Children with velocardiofacial syndrome had significantly smaller average temporal lobe, superior temporal gyrus, and hippocampal volumes than normal comparison children, although these differences were commensurate with a lower overall brain size in the affected children. In a cross-sectional analysis, children with velocardiofacial syndrome exhibited aberrant volumetric reductions with age that were localized to the temporal lobe and left hippocampal regions. CONCLUSIONS: Abnormal temporal lobe and hippocampal development in velocardiofacial syndrome is potentially concordant with MRI findings in the schizophrenia literature. Temporal lobe and mesial temporal structures may represent a shared substrate for the effects of the 22q11.2 deletion and for the complex etiological pathways that lead to schizophrenia. Longitudinal research may help determine which children with velocardiofacial syndrome are at risk for serious psychiatric illness in adulthood.
Blockade of the natriuretic peptide receptor guanylyl cyclase-A inhibits NF-κB activation and alleviates myocardial ischemia/reperfusion injury
Authors: Takehiko Izumi, Yoshihiko Saito, Ichiro Kishimoto, Masaki Harada, Koichiro Kuwahara, Ichiro Hamanaka, Nobuki Takahashi, Rika Kawakami, Yuhao Li, Genzo Takemura, Hisayoshi Fujiwara, David L. Garbers, Seibu Mochizuki, Kazuwa Nakao
Journal: Journal of Clinical Investigation (2001)

Acute myocardial infarction (AMI) remains the leading cause of death in developed countries. Although reperfusion of coronary arteries reduces mortality, it is associated with tissue injury. Endothelial P-selectin–mediated infiltration of neutrophils plays a key role in reperfusion injury. However, the mechanism of the P-selectin induction is not known. Here we show that infarct size after ischemia/reperfusion was significantly smaller in mice lacking guanylyl cyclase-A (GC-A), a natriuretic peptide receptor. The decrease was accompanied by decreases in neutrophil infiltration in coronary endothelial P-selectin expression. Pretreatment with HS-142-1, a GC-A antagonist, also decreased infarct size and P-selectin induction in wild-type mice. In cultured endothelial cells, activation of GC-A augmented H2O2-induced P-selectin expression. Furthermore, ischemia/reperfusion–induced activation of NF-κB, a transcription factor that is known to promote P-selectin expression, is suppressed in GC-A–deficient mice. These results suggest that inhibition of GC-A alleviates ischemia/reperfusion injury through suppression of NF-κB–mediated P-selectin induction. This novel, GC-A–mediated mechanism of ischemia/reperfusion injury may provide the basis for applying GC-A blockade in the clinical treatment of reperfusion injury.
Female-Biased Expression on the X Chromosome as a Key Step in Sex Chromosome Evolution in Threespine Sticklebacks
Authors: Erica H. Leder, Jose M. Cano, Tuomas Leinonen, Robert B. O'Hara, Mikko Nikinmaa, Craig R. Primmer, Juha Merilä
Journal: Molecular Biology and Evolution (2010)

Given that the genome of males and females are almost identical with the exception of genes on the Y (or W) chromosome or sex-determining alleles (in organisms without sex chromosomes), it is likely that many downstream processes resulting in sexual dimorphism are produced by changes in regulation. In early stages of sex chromosome evolution, as the Y-chromosome degenerates, gene expression should be significantly impacted for genes residing on the sex chromosome pair as regulatory mutations accumulate. However, this has rarely been examined because most model organisms have clearly diverged sex chromosomes. Fish provide a unique opportunity to examine the evolution of sex chromosomes because genetic sex determination has evolved quite recently in some groups of fish. We compared sex-specific transcription in threespine stickleback (Gasterosteus aculeatus) liver tissue using a long-oligo microarray. Of the 1,268 genes that were differentially expressed between sexes, a highly significant proportion (23%) was concentrated on chromosome 19, corresponding to the recently described nascent sex chromosomes. The sex-biased genes are enriched for different functional categories in males and females, although there is no specific functional enrichment on the sex chromosomes. Female-biased genes are concentrated at one end of the sex chromosome, corresponding to a deletion in the Y, suggesting a lack of global dosage compensation. Prior research on threespine sticklebacks has demonstrated various degrees of dissimilarity in upstream regions of genes on the Y providing a potential mechanism for the observed patterns of female-biased expression. We hypothesize that degeneration of the Y chromosome results in regulatory mutations that create a sex-specific expression pattern and that this physical concentration of sex-biased expression on the nascent sex chromosome may be a key feature characterizing intermediate phases of sex chromosome evolution.
Authority consults public on paying women £1000 to donate eggs
Authors: Rebecca Coombes
Journal: BMJ (2004)

Rewarding women who donate eggs with up to £1000 and relaxing rules on importing gametes could help UK fertility clinics that are struggling to find willing donors, the Human Fertilisation and Embryology Authority said last week.

The suggestions are part of a public consultation by the authority on gametes and embryo donation. It comes as clinics face further challenges in recruiting donors. From April 2005 the anonymity of donors will no longer be protected, and their identity could be disclosed once their genetic children reach the age of 18.

A survey of UK clinics carried out by …
Expression and activation of TGF- isoforms in acute allergen-induced remodelling in asthma
Authors: A. Torrego, M. Hew, T. Oates, M. Sukkar, K. Fan Chung
Journal: Thorax (2007)

Airway wall remodelling and inflammation are features of chronic asthma. Transforming growth factor beta (TGF-beta) has been implicated in these processes.To determine the effect of allergen challenge on airway inflammation and remodelling and whether TGF-beta isoforms and the Smad signalling pathways are involved.Thirteen patients with atopic asthma underwent inhalational challenge with 0.9% saline, followed by allergen 3-4 weeks later. After both challenges, fibreoptic bronchoscopy was undertaken to obtain bronchial biopsies and tissue samples were processed for immunohistochemistry and examined by microscopy.Forced expiratory volume in 1 s (FEV(1)) fell after allergen challenge (mean (SE) -28.1 (0.9)% at 30 min with a late response at 7 hours (-23.0 (1.2)%). Allergen challenge caused an increase in neutrophils and eosinophils in the bronchial mucosa compared with saline. Sub-basement membrane (SBM) thickness did not change after allergen, but tenascin deposition in SBM was increased. Intranuclear (activated) Smad 2/3 and Smad 4 detected by immunohistochemistry were increased after allergen challenge in epithelial and subepithelial cells of bronchial biopsies. No inhibitory Smad (Smad 7) protein was detected. TGF-beta isoforms 1, 2 and 3 were expressed predominantly in bronchial epithelium after saline and allergen challenges, but only TGF-beta(2) expression was increased after allergen. Double immunostaining showed an increase in TGF-beta(2) positive eosinophils and neutrophils but not in TGF-beta(1) positive eosinophils and neutrophils after allergen challenge.TGF-beta(2) may contribute to the remodelling changes in allergic asthma following single allergen exposure.
Mutation analysis of ATP2C1 gene in Taiwanese patients with Hailey-Hailey disease
Authors: S-C. Chao, Y-M. Tsai, M-H. Yang
Journal: British Journal of Dermatology (2002)

Journal Article Mutation analysis of ATP2C1 gene in Taiwanese patients with Hailey–Hailey disease Get access S‐C. Chao, S‐C. Chao Department of Dermatology, College of Medicine, National Cheng Kung University Hospital, 138 Sheng‐Li Road, 704 Tainan, Taiwan Sheau‐Chiou Chao. E‐mail: joly@mail.ncku.edu.tw Search for other works by this author on: Oxford Academic Google Scholar Y‐M. Tsai, Y‐M. Tsai Department of Dermatology, College of Medicine, National Cheng Kung University Hospital, 138 Sheng‐Li Road, 704 Tainan, Taiwan Search for other works by this author on: Oxford Academic Google Scholar M‐H. Yang M‐H. Yang Department of Dermatology, College of Medicine, National Cheng Kung University Hospital, 138 Sheng‐Li Road, 704 Tainan, Taiwan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 146, Issue 4, 1 April 2002, Pages 595–600, https://doi.org/10.1046/j.1365-2133.2002.04697.x Published: 01 April 2002 Article history Accepted: 04 December 2001 Published: 01 April 2002
Drug-Eluting Balloon in Peripheral Intervention for Below the Knee Angioplasty Evaluation (DEBATE-BTK)
Authors: Francesco Liistro, Italo Porto, Paolo Angioli, Simone Grotti, Lucia Ricci, Kenneth Ducci, Giovanni Falsini, Giorgio Ventoruzzo, Filippo Turini, Guido Bellandi, Leonardo Bolognese
Journal: Circulation (2013)

Background— The 1-year restenosis rate after balloon angioplasty of long lesions in below-the-knee arteries may be as high as 70%. Our aim was to investigate the efficacy of a paclitaxel drug-eluting balloons versus conventional percutaneous transluminal angioplasty (PTA) for the reduction of restenosis in diabetic patients with critical limb ischemia undergoing endovascular intervention of below-the-knee arteries. Methods and Results— The Drug-Eluting Balloon in Peripheral Intervention for Below the Knee Angioplasty Evaluation (DEBATE-BTK) is a randomized, open-label, single-center study comparing drug-eluting balloons and PTA. Inclusion criteria were diabetes mellitus, critical limb ischemia (Rutherford class 4 or higher), significant stenosis or occlusion &gt;40 mm of at least 1 below-the-knee vessel with distal runoff, and life expectancy &gt;1 year. Binary in-segment restenosis at a 1-year angiographic or ultrasonographic follow-up was the primary end point. Clinically driven target lesion revascularization, major amputation, and target vessel occlusion were the secondary end points. One hundred thirty-two patients with 158 infrapopliteal atherosclerotic lesions were enrolled. Mean length of the treated segments was 129±83 mm in the drug-eluting balloon group compared with 131±79 mm in the PTA group ( P =0.7). Binary restenosis, assessed by angiography in &gt;90% of patients, occurred in 20 of 74 lesions (27%) in the drug-eluting balloon group compared with 55 of 74 lesions (74%) in the PTA group ( P &lt;0.001); target lesion revascularization, in 12 (18%) versus 29 (43%; P =0.002); and target vessel occlusion, in 12 (17%) versus 41 (55%; P &lt;0.001). Only 1 major amputation occurred, in the PTA group ( P =0.9). Conclusions— Drug-eluting balloons compared with PTA strikingly reduce 1-year restenosis, target lesion revascularization, and target vessel occlusion in the treatment of below-the-knee lesions in diabetic patients with critical limb ischemia. Clinical Trial Registration— URL: http://ClinicalTrials.gov . Unique identifier: NCT01558505.
Biomechanics, diagnosis, and treatment outcome in inflammatory myopathy presenting as oropharyngeal dysphagia
Authors: R B Williams
Journal: Gut (2003)

In patients with inflammatory myopathy and dysphagia, our aims were to determine: (1) the diagnostic utility of clinical and laboratory indicators; (2) the biomechanical properties of the pharyngo-oesophageal segment; (3) the usefulness of pharyngeal videomanometry in distinguishing neuropathic from myopathic dysphagia; and (4) clinical outcome.Clinical, laboratory, and videomanometric assessment was performed in 13 patients with myositis and dysphagia, in 17 disease controls with dysphagia (due to proven CNS disease), and in 22 healthy age matched controls. The diagnostic accuracy of creatine kinase (CPK), erythrocyte sedimentation rate, antinuclear antibody, and electromyography (EMG) were compared with the gold standard muscle biopsy. The biomechanical properties of the pharyngo-oesophageal segment were assessed by videomanometry.Mean time from dysphagia onset to the diagnosis of myositis was 55 months (range 1-180). One third had no extrapharyngeal muscle weakness; 25% had normal CPK, and EMG was unhelpful in 28%. Compared with neurogenic controls, myositis patients had more prevalent cricopharyngeal restrictive disorders (69% v 14%; p=0.0003), reduced upper oesophageal sphincter (UOS) opening (p=0.01), and elevated hypopharyngeal intrabolus pressures (p=0.001). Videomanometric features favouring a myopathic over a neuropathic aetiology were: preserved pharyngeal swallow response, complete UOS relaxation, and normal swallow coordination. The 12 month mortality was 31%.The notable lack of supportive clinical signs and significant false negative rates for laboratory tests contribute to the marked delay in diagnosis. The myopathic process is strongly associated with restricted sphincter opening suggesting that cricopharyngeal disruption is a useful adjunct to immunosuppressive therapy. The condition has a poor prognosis.
Systemic Immune-Inflammation Index Predicts Prognosis of Patients after Curative Resection for Hepatocellular Carcinoma
Authors: Bo Hu, Xin-Rong Yang, Yang Xu, Yun-Fan Sun, Chao Sun, Wei Guo, Xin Zhang, Wei-Min Wang, Shuang-Jian Qiu, Jian Zhou, Jia Fan
Journal: Clinical Cancer Research (2014)

We developed a novel systemic immune-inflammation index (SII) based on lymphocyte, neutrophil, and platelet counts and explored its prognostic value in hepatocellular carcinoma (HCC).The SII was developed based on a retrospective study of 133 patients with HCC undergoing resection between 2005 and 2006, and validated in a prospective study of 123 patients enrolled from 2010 to 2011. The circulating tumor cell (CTC) level in the validation cohort was measured using the CellSearch system. Prediction accuracy was evaluated with area under the receiver operating characteristic curve (AUC).An optimal cutoff point for the SII of 330 × 10(9) stratified the patients with HCC into high (≥330) and low SII (<330) groups in the training cohort. Univariate and multivariate analyses revealed the SII was an independent predictor for overall survival and relapse-free survival, and prognostic for patients with negative α-fetoprotein and Barcelona Clinic Liver Cancer stage 0+A. The AUCs of the SII for survival and recurrence were higher than other conventional clinical indices. An SII ≥ 330 was significantly associated with vascular invasion, large tumors, and early recurrence. CTC levels were significantly higher in the SII ≥ 330 group (1.71 ± 0.34 vs. 4.37 ± 1.04, P = 0.029). In patients with detectable CTCs, those with SII ≥ 330 had higher recurrence rates and shorter survival time than patients with SII < 330.The SII was a powerful prognostic indicator of poor outcome in patients with HCC and is a promising tool for HCC treatment strategy decisions. The dismal outcome in patients with high SII scores might be related to higher CTC levels.
Chromatin conformation signatures of cellular differentiation
Authors: James Fraser, Mathieu Rousseau, Solomon Shenker, Maria A Ferraiuolo, Yoshihide Hayashizaki, Mathieu Blanchette, Josée Dostie
Journal: Genome biology (2009)

Abstract One of the major genomics challenges is to better understand how correct gene expression is orchestrated. Recent studies have shown how spatial chromatin organization is critical in the regulation of gene expression. Here, we developed a suite of computer programs to identify chromatin conformation signatures with 5C technology http://Dostielab.biochem.mcgill.ca . We identified dynamic HoxA cluster chromatin conformation signatures associated with cellular differentiation. Genome-wide chromatin conformation signature identification might uniquely identify disease-associated states and represent an entirely novel class of human disease biomarkers.
Socioeconomic Disadvantage and Change in Blood Pressure Associated With Aging
Authors: Ana V. Diez Roux, Lloyd Chambless, Sharon Stein Merkin, Donna Arnett, Marsha Eigenbrodt, F. Javier Nieto, Moyses Szklo, Paul Sorlie
Journal: Circulation (2002)

Background — Few studies have examined how the longitudinal change in blood pressure associated with aging differs across social groups within industrialized countries. Methods and Results — Data from the Atherosclerosis Risk In Communities Study were used to investigate differences in the incidence of hypertension and in aging-related changes in blood pressure by neighborhood and individual socioeconomic factors over a 9-year follow-up. Disadvantage in multiple socioeconomic dimensions was associated with the greatest risk of developing hypertension (age- and sex-adjusted hazard ratio [HR] and 95% CI: HR 1.95, 95% CI 1.38 to 2.75 in whites and HR 1.43, 95% CI 0.96 to 2.13 in blacks). Aging-related increases in systolic blood pressure were inversely associated with socioeconomic position in whites (mean [SEM] 5-year increase in systolic blood pressure 7 [0.7] mm Hg in the most disadvantaged category and 5.4 [0.4] mm Hg in the most advantaged category). In whites, low socioeconomic position was also associated with more rapid declines in diastolic blood pressure after 50 years of age. Socioeconomic differences in hypertension incidence and changes in systolic blood pressure were reduced after adjustment for baseline blood pressure. Conclusion — The change in blood pressure associated with aging varies by social groups within the United States.
Molecular analysis of patient and carrier genes with congenital steroid 21-hydroxylase deficiency by using polymerase chain reaction and single strand conformation polymorphism.
Authors: T Tajima, K Fujieda, K Nakayama, Y Fujii-Kuriyama
Journal: Journal of Clinical Investigation (1993)

Steroid 21-hydroxylase deficiency is a major cause of congenital adrenal hyperplasia and is caused by genetic impairment of this enzyme. Since approximately 80% of cases are caused by point mutations of the CYP21B (CYP21A2) gene, whereas the remaining 20% are due to deletion of this gene, we used the polymerase chain reaction single strand conformation polymorphism technique for rapid and accurate diagnosis of this disease. Of 23 patients examined, 1 had a hemizygous CYP21B gene. 18 patient's genes localized their harmful mutations or deletion on both the alleles, while 4 of them found their causative mutations on one of the two alleles, and 1 failed to find any responsible mutation. All the mutations (four nucleotide substitutions) detected are also found in the CYP21A (CYP21A1) pseudogene. A mutation at the intron 2 site is most prevalent in both salt-wasting and simple virilizing forms of the disease, and accounts for 37% of the patient's genes (17/46). Pedigree analysis of these mutations revealed that the mutations (at least four of them) occurred de novo at a considerable frequency on both the paternally and maternally inherited chromosomes. This result could explain occasional discordance of the diagnosis using HLA typing with the clinical symptoms.
Experimental Pulmonary Embolism due to Red Cell Aggregation
Authors: A. De Bono, N. Gazetopoulos
Journal: Thorax (1964)

This method of producing red cell clumps in vivo is also being used to produce chronic pulmonary hypertension, and to studv the effects of red cell aggregation on other organs such as the heart.brain, gut, and kidney.This will be described in subsequent papers.