tbuckley/cabot-search huggingface dataset:
Metabolic abnormalities in skeletal muscle of patients receiving zidovudine therapy observed by 31P in vivo magnetic resonance spectroscopy.
Authors: T M Sinnwell, K Sivakumar, S Soueidan, C Jay, J A Frank, A C McLaughlin, M C Dalakas
Journal: Journal of Clinical Investigation (1995)

Patients on long-term zidovudine (AZT) therapy experience muscle fatigue and weakness attributed to AZT-induced mitochondrial toxicity in skeletal muscle. To determine if the clinico-pathological abnormalities in these patients correspond to abnormal muscle energy metabolism, we used 31P in vivo magnetic resonance spectroscopy to follow phosphorylated metabolites during exercise. We studied 19 normal volunteers, 6 HIV-positive patients never treated with AZT, and 9 HIV-positive patients who had been treated with AZT for a mean period of 33 mo (range 12-48 mo) and had muscle biopsy-proven AZT-myopathy with abnormal mitochondria. Changes in phosphocreatine, ATP, and intracellular pH in the gastrocnemius muscle were followed during a graded steady state exercise protocol, and the recovery of phosphocreatine was followed on cessation of exercise. We found that graded steady state exercise produced a greater depletion of muscle phosphocreatine levels in the AZT-treated patients, compared to either HIV-positive patients who were not treated with AZT or normal controls. No differences in the effects of steady state exercise on muscle phosphocreatine levels were observed between the control group and the HIV-positive patients who had not been treated with AZT. The results suggest that the effect of AZT on muscle energy metabolism is significant, and similar to the effect observed in patients with known mitochondrial myopathies. Using a well-known model for control of mitochondrial metabolism, the observed differences in steady state phosphocreatine levels during exercise suggest that AZT treatment decreases the maximal work output and the maximal rate of muscle ATP synthesis.
Gene Alterations Identified by Expression Profiling in Tumor-Associated Endothelial Cells from Invasive Ovarian Carcinoma
Authors: Chunhua Lu, Tomas Bonome, Yang Li, Aparna A. Kamat, Liz Y. Han, Rosemarie Schmandt, Robert L. Coleman, David M. Gershenson, Robert B. Jaffe, Michael J. Birrer, Anil K. Sood
Journal: Cancer Research (2007)

Therapeutic strategies based on antiangiogenic approaches are beginning to show great promise in clinical studies. However, full realization of these approaches requires identification of key differences in gene expression between endothelial cells from tumors versus their normal counterparts. Here, we examined gene expression differences in purified endothelial cells from 10 invasive epithelial ovarian cancers and 5 normal ovaries using Affymetrix U133 Plus 2.0 microarrays. More than 400 differentially expressed genes were identified in tumor-associated endothelial cells. We selected and validated 23 genes that were overexpressed by 3.6- to 168-fold using real-time reverse transcription-PCR and/or immunohistochemistry. Among these, the polycomb group protein enhancer of Zeste homologue 2 (EZH2), the Notch ligand Jagged1, and PTK2 were elevated 3- to 4.3-fold in tumor-associated endothelial cells. Silencing these genes individually with small interfering RNA blocked endothelial cell migration and tube formation in vitro. The present study shows that tumor and normal endothelium differ at the molecular level, which may have significant implications for the development of antiangiogenic therapies.
Site of Origin and Molecular Substrate of Atrioventricular Junctional Rhythm in the Rabbit Heart
Authors: Halina Dobrzynski, Vladimir P. Nikolski, Alexandre T. Sambelashvili, Ian D. Greener, Mitsuru Yamamoto, Mark R. Boyett, Igor R. Efimov
Journal: Circulation Research (2003)

During failure of the sinoatrial node, the heart can be driven by an atrioventricular (AV) junctional pacemaker. The position of the leading pacemaker site during AV junctional rhythm is debated. In this study, we present evidence from high-resolution fluorescent imaging of electrical activity in rabbit isolated atrioventricular node (AVN) preparations that, in the majority of cases (11 out of 14), the AV junctional rhythm originates in the region extending from the AVN toward the coronary sinus along the tricuspid valve (posterior nodal extension, PNE). Histological and immunohistochemical investigation showed that the PNE has the same morphology and unique pattern of expression of neurofilament160 (NF160) and connexins (Cx40, Cx43, and Cx45) as the AVN itself. Block of the pacemaker current, If, by 2 mmol/L Cs+ increased the AV junctional rhythm cycle length from 611+/-84 to 949+/-120 ms (mean+/-SD, n=6, P<0.001). Immunohistochemical investigation showed that the principal If channel protein, HCN4, is abundant in the PNE. As well as the AV junctional rhythm, the PNE described in this study may also be involved in the slow pathway of conduction into the AVN as well as AVN reentry, and the predominant lack of expression of Cx43 as well as the presence of Cx45 in the PNE shown could help explain its slow conduction.
Randomized Parallel Study of Doxorubicin Plus Paclitaxel and Doxorubicin Plus Cyclophosphamide As Neoadjuvant Treatment of Patients With Breast Cancer
Authors: Véronique Diéras, Pierre Fumoleau, Gilles Romieu, Michèle Tubiana-Hulin, Moïse Namer, Louis Mauriac, Jean-Paul Guastalla, Eric Pujade-Lauraine, Pierre Kerbrat, Philippe Maillart, Frédérique Pénault-Llorca, Marc Buyse, Pierre Pouillart
Journal: Journal of Clinical Oncology (2004)

Purpose This randomized, noncomparative, parallel-group study was designed to evaluate the pathologic complete response (pCR) rate of combined doxorubicin plus paclitaxel (AP) and doxorubicin plus cyclophosphamide (AC) as neoadjuvant chemotherapy in patients with previously untreated breast cancer who were unsuitable for conservative surgery. Patients and Methods A total of 200 patients with T2-3, N0-1, M0 disease were randomly assigned in a 2:1 ratio to receive preoperative chemotherapy with either doxorubicin 60 mg/m 2 plus paclitaxel 200 mg/m 2 as a 3-hour infusion (AP) or doxorubicin 60 mg/m 2 plus cyclophosphamide 600 mg/m 2 (AC) every 3 weeks for 4 courses followed by surgery. Results A pCR (eradication of invasive carcinoma in tumor and in axillary lymph nodes) was found in 16% and 10% of patients in the AP and AC arms, respectively, by study center pathologists, and in 8% and 6% of patients, respectively, by independent pathologists. Patients with pCRs tended to have unifocal disease, tumors with negative hormonal receptor status, and less differentiation (Scarff, Bloom, and Richardson scale grade 3). Breast-conserving surgery was performed in 58% and 45% of patients in the AP and AC arms, respectively. An objective clinical response was achieved in 89% of patients in the AP arm and 70% in the AC arm. At a median follow-up of 31 months, disease-free survival (DFS) was higher in patients who reached pCR versus those without pCR (91% v 70%). Conclusion The encouraging pathologic and clinical responses of patients with breast cancer after neoadjuvant chemotherapy with doxorubicin plus paclitaxel warrant additional investigation of paclitaxel in the neoadjuvant setting of breast cancer management.
Familial Breast Cancers without Mutations in BRCA1 or BRCA2 Have Low Cyclin E and High Cyclin D1 in Contrast to Cancers in BRCA Mutation Carriers
Authors: Kirsimari Aaltonen, Carl Blomqvist, Rose-Marie Amini, Hannaleena Eerola, Kristiina Aittomäki, Päivi Heikkilä, Heli Nevanlinna
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We analyzed the expression of critical cell cycle regulators cyclin E and cyclin D1 in familial breast cancer, focusing on BRCA mutation–negative tumors. Cyclin E expression in tumors of BRCA1 or BRCA2 carriers is higher, and cyclin D1 expression lower, than in sporadic tumors. In familial non-BRCA1/2 tumors, cyclin E and cyclin D1 expression has not been studied. Experimental Design: Cyclin E and cyclin D1 immunohistochemical expression was studied in tissue microarrays consisting of 53 BRCA1, 58 BRCA2, 798 familial non-BRCA1/2, and 439 sporadic breast tumors. Results: In univariate analysis, BRCA1 tumors had significantly more frequently high cyclin E (88%) and low cyclin D1 (84%) expression than sporadic (54% and 49%, respectively) or familial non-BRCA1/2 (38% and 45%, respectively) tumors. BRCA2 tumors had significantly more frequently low cyclin D1 expression (68%) than sporadic or familial non-BRCA1/2 tumors and significantly more frequently high cyclin E expression than familial non-BRCA1/2 tumors. In a logistic regression model, cyclin expression, early age of onset, and estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) status were the independent factors most clearly distinguishing tumors of BRCA1 mutation carriers from other familial breast cancers. High cyclin E and low cyclin D1 expression were also independent predictors of BRCA2 mutation when compared with familial non-BRCA1/2 tumors. Most interestingly, lower frequency of high cyclin E expression independently distinguished familial non-BRCA1/2 tumors also from sporadic ones. Conclusions: Cyclin E and cyclin D1 expression distinguishes non-BRCA1/2 tumors from both sporadic and BRCA1- and BRCA2-associated tumors and may reflect different predisposition and pathogenesis in these groups.
The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200–dependent pathway in mice
Authors: Yanan Yang, Young-Ho Ahn, Don L. Gibbons, Yi Zang, Wei Lin, Nishan Thilaganathan, Cristina A. Alvarez, Daniel C. Moreira, Chad J. Creighton, Philip A. Gregory, Gregory J. Goodall, Jonathan M. Kurie
Journal: Journal of Clinical Investigation (2011)

Epithelial tumor cells transit to a mesenchymal state in response to extracellular cues, in a process known as epithelial-to-mesenchymal transition (EMT). The precise nature of these cues has not been fully defined, an important issue given that EMT is an early event in tumor metastasis. Here, we have found that a population of metastasis-prone mouse lung adenocarcinoma cells expresses Notch and Notch ligands and that the Notch ligand Jagged2 promotes metastasis. Mechanistically, Jagged2 was found to promote metastasis by increasing the expression of GATA-binding (Gata) factors, which suppressed expression of the microRNA-200 (miR-200) family of microRNAs that target the transcriptional repressors that drive EMT and thereby induced EMT. Reciprocally, miR-200 inhibited expression of Gata3, which reversed EMT and abrogated metastasis, suggesting that Gata3 and miR-200 are mutually inhibitory and have opposing effects on EMT and metastasis. Consistent with this, high levels of Gata3 expression correlated with EMT in primary tumors from 2 cohorts of lung adenocarcinoma patients. These findings reveal what we believe to be a novel Jagged2/miR-200–dependent pathway that mediates lung adenocarcinoma EMT and metastasis in mice and may have implications for the treatment of human epithelial tumors.
Randomised controlled trial of effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux: Bristol helicobacter project
Authors: R. F Harvey
Journal: BMJ (2004)

Objectives To investigate the effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux.Design Cross sectional study, followed by a randomised placebo controlled trial.Setting Seven general practices in Bristol, England.Participants 10 537 people, aged 20-59 years, with and without H pylori infection (determined by the 13 C-urea breath test).Main outcome measures Prevalence of heartburn and gastro-oesophageal acid reflux at baseline and two years after treatment to eradicate H pylori infection.Results At baseline, H pylori infection was associated with increased prevalence of heartburn (odds ratio 1.14, 95% confidence interval 1.05 to 1.23) but not reflux (1.05, 0.97 to 1.14).In participants with H pylori infection, active treatment had no effect on the overall prevalence of heartburn (0.99, 0.88 to 1.12) or reflux (1.04, 0.91 to 1.19) and did not improve pre-existing symptoms of heartburn or reflux.Conclusions H pylori infection is associated with a slightly increased prevalence of heartburn but not reflux.Treatment to eradicate H pylori has no net benefit in patients with heartburn or gastro-oesophageal reflux.
Quantitative ER and PgR Assessment as Predictors of Benefit from Lapatinib in Postmenopausal Women with Hormone Receptor–Positive, HER2-Negative Metastatic Breast Cancer
Authors: Richard S. Finn, Michael F. Press, Judy Dering, Lisa O'Rourke, Allison Florance, Catherine Ellis, Anne-Marie Martin, Stephen Johnston
Journal: Clinical Cancer Research (2013)

Lapatinib, a dual epidermal growth factor receptor (EGFR) and HER2 inhibitor, remains unproven in non-HER2-amplified metastatic breast cancer (MBC). EGF30008, a phase III trial of letrozole and lapatinib versus letrozole and placebo, demonstrated that lapatinib significantly improves outcome for postmenopausal women with HER2-amplified, but not HER2-negative, MBC. The hypothesis that low hormone receptor status is associated with benefit in this HER2-negative cohort was tested.A blinded retrospective biomarker evaluation used immunohistochemistry (IHC) to semiquantify estrogen receptor (ER) and progesterone receptor (PgR) expression (n = 821/952). HER2 status was determined by IHC and confirmed by FISH (n = 326). Effects of these biomarkers on progression-free survival (PFS) were examined in patients with available tissue.In HER2-negative, ER-positive MBC, median PFS was analyzed by ER and PgR expression (H-score) by quartile (Q). There was significant improvement in patients with low ER expression (Q1, H-score <160) with lapatinib and letrozole (13.6 vs. 6.7 months; P = 0.01). No benefit was associated with stronger ER expression (Q2/3, H-score ≥ 160 and <250; 13.6 vs. 14.2 months; Q4, H-score ≥ 250; 11.2 vs. 14.2 months). There was no association between PgR H-score and benefit from lapatinib.In postmenopausal patients with advanced hormone receptor-positive disease, weak ER expression is associated with worse outcome with letrozole treatment compared with the combination. The addition of lapatinib significantly improved PFS for this patient subgroup and augments data supporting interaction between steroid hormone and peptide hormone signaling. A prospective study validating this hypothesis is required.
Post-transfusional anti-HCV-negative non-A non-B hepatitis (II) serological and polymerase chain reaction analysis for hepatitis C and hepatitis B viruses
Authors: Valerie Thiers, Francoise Lunel, Dominique Valla, Naibh Azar, Catherine Fretz, Lionel Frangeul, Jean-Marie Huraux, Pierre Opolon, Christian Brechot
Journal: Journal of Hepatology (1993)
A Prospective Study of Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) and Risk of Colorectal Cancer
Authors: Raaj S. Mehta, Mingyang Song, Navya Bezawada, Kana Wu, Xabier Garcia-Albeniz, Teppei Morikawa, Charles S. Fuchs, Shuji Ogino, Edward L. Giovannucci, Andrew T. Chan
Journal: JNCI Journal of the National Cancer Institute (2014)

Chronic inflammation plays a role in the development of colorectal cancer (CRC). The novel plasma inflammatory biomarker macrophage inhibitory cytokine-1 (MIC-1, GDF15) may have a direct mechanistic role in colorectal carcinogenesis. We conducted a prospective, nested, case–control study of incident CRC among men and women who provided a prediagnostic blood specimen. We used an enzyme-linked immunosorbent assay to measure MIC-1 and examined associations between quintiles of MIC-1 and CRC using logistic regression adjusted for matching factors (age and date of blood draw), risk factors, and other plasma inflammatory markers. We also assessed the relationship between MIC-1 levels and prostaglandin-endoperoxide synthase 2 (PTGS2)/cyclooxygenase-2 (COX-2) enzyme status in tumors with available tissue for analysis. All statistical tests were two-sided. Compared with men and women within the lowest quintile of plasma MIC-1, the multivariable relative risk (RR) for CRC was 1.93 (95% confidence interval [CI] = 1.27 to 2.94) for the highest quintile (Plinear trend = .004). In an exploratory analysis, we found that among individuals with high plasma MIC-1 levels (quintiles 2–5), compared with nonuse, regular use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with a lower risk of PTGS2-positive CRC (multivariable RR = 0.60; 95% confidence interval = 0.41 to 0.88) but not PTGS2-negative CRC (multivariable RR = 1.21; 95% CI = 0.71 to 2.07). In contrast, among individuals with low MIC-1 levels (quintile 1), aspirin and NSAID use was not associated with a lower risk of PTGS2-positive CRC (multivariable RR = 0.57; 95% CI = 0.21 to 1.54) or PTGS2-negative CRC (multivariable RR = 1.41; 95% CI = 0.47 to 4.23). Our results support an association between higher levels of circulating MIC-1 (GDF15) and CRC. Aspirin/NSAID use appeared to lower risk of PTGS2-positive cancers, particularly among individuals with high levels of circulating MIC-1.
THE HISTOLOGY OF EQUINE ENCEPHALOMYELITIS
Authors: E. Weston Hurst
Journal: The Journal of Experimental Medicine (1934)

The virus of equine encephalomyelitis (eastern strain) evokes in the horse, calf, sheep and dog an unusually intense encephalomyelitis characterized by acute primary degeneration of nerve cells, the appearance in neurons of the brain stem and elsewhere of nuclear inclusions resembling those in Borna disease and poliomyelitis, polymorphonuclear infiltration in the nervous tissues with early microglial proliferation, and perivascular cuffing with mononuclears and polymorphonuclears in varying proportions. The grey matter is affected more than the white. Lesions may be less marked in the striatum, brain stem and cord than in the cerebral cortex, thalamus and hypothalamic region, and are always of low grade in the cerebellum. Meningeal infiltration is secondary. Similar changes produced in the horse by the western strain of virus are less intense and extensive. In the guinea pig, rabbit and mouse, the eastern virus causes an acute encephalomyelitis which, as is usual in neurotropic virus diseases of these lowly species, has a special tendency to affect the higher olfactory centers. In addition to inclusions in the nerve cells, tiny oxyphilic bodies occur with less frequency in the glial and mesodermal nuclei of the guinea pig. In this animal, too, interstitial or bronchopneumonia may complicate the picture. In the guinea pig the disease resulting from infection with the western virus may be indistinguishable from that due to the eastern.
Sialochemistry of patients with autoimmune rheumatic disease with and without histological manifestations of Sjogren's syndrome.
Authors: E B Tsianos, A G Tzioufas, A K Mavridis, A K Sarras, C S Papadimitriou, O Tsolas, H M Moutsopoulos
Journal: Annals of the Rheumatic Diseases (1985)

Fifty-one patients with autoimmune rheumatic diseases underwent biopsy of the labial minor salivary glands. These patients were divided according to histopathology of lip biopsies into three groups (negative lip biopsy, 1+ and 2+). From all the patients stimulated parotid salivary flow was measured. In the saliva sodium, potassium, magnesium, alpha-amylase, and immunoglobulin levels (IgA, IgG, IgM) were measured. It is shown that patients with advanced chronic inflammatory disease of the minor salivary glands have decreased stimulated salivary flow. However, no statistically significant differences were observed in the biochemical markers tested between the histopathological groups examined.
Music and video: means to success
Authors: N Vijay Mohan, A Pallavi
Journal: British Journal of Sports Medicine (2010)

Young people are typically confident in the use of the latest technologies and because many aspiring athletes are from this age range, sport psychologists and coaches should consider using this technology in their work. A key question for applied sport psychology practitioners and coaches, therefore, is what technologies will be used by and beneficial for athletes? Here, we deal with MP3 technology to enhance performance. The use of MP3 technology by athletes is often seen as an integral part of mental preparation. Typically, music folders are arranged on an MP3 player to contain music of different genres. However, we assist athletes in developing music folders with specific purposes. For example, folders may be established containing music that is intended to relax, motivate energies, develop confidence or a combination of these. The advent of video MP3 players has introduced further possibilities for the use of technology among sport and exercise psychologists, coaches and athletes. Within our practice, we use video iPod players to reinforce correct technique, direct attention to key goals/objectives and motivate athletes. For example, images of the athlete performing can be merged with images of the role models they aspire to beat. Nowadays as computer technology becomes more sophisticated the ability to produce videos with associated music becomes easier. Athletes value technology and coaches can build upon this by demonstrating how it can be used effectively to enhance performance.
The Novel Gene <i>EG-1</i> Stimulates Cellular Proliferation
Authors: Ming Lu, Liping Zhang, Raymond Scott Maul, Maryam R. Sartippour, Andrew Norris, Julian Whitelegge, Jian Yu Rao, Mai N. Brooks
Journal: Cancer Research (2005)

Abstract We recently discovered a novel gene and named it endothelial-derived gene 1 (EG-1). Previously, we have shown that the expression of EG-1 is significantly elevated in the epithelial cells of breast cancer, colorectal cancer, and prostate cancer. Here, we report that EG-1 can stimulate cellular proliferation. Transfection experiments which overexpressed the full-length EG-1 gene in human embryonic kidney HEK-293 cells or human breast cancer cell lines resulted in significantly increased in vitro proliferation, in comparison with transfection with empty vectors. On the other hand, small interfering RNA cotransfection resulted in inhibition of proliferation. S.c. xenograft assays were carried out in a severe combined immunodeficient mouse model. We found that injection of high EG-1 expressing HEK-293 clones resulted in significantly larger tumors, in comparison with clones carrying the empty vectors. To further clarify the function of this gene, we investigated its interaction with Src and members of the mitogen-activated protein kinase (MAPK) family. Immunoprecipitation with anti-Src antibody, followed by immunoblotting with anti–EG-1 antibody, showed an association between these two molecules. Overexpression of EG-1 was correlated with activation of the following kinases: extracellular signal-regulated kinases 1 and 2, c-jun-NH2-kinase, and p38. These observations collectively support the hypothesis that the novel gene EG-1 is a positive stimulator of cellular proliferation, and may possibly be involved in signaling pathways involving Src and MAPK activation.