tbuckley/cabot-search huggingface dataset:
Acute phase HBV-specific T cell responses associated with HBV persistence after HBV/HCV coinfection
Authors: Simona Urbani, Carolina Boni, Barbara Amadei, Paola Fisicaro, Simona Cerioni, Maria Antonietta Valli, Gabriele Missale, Carlo Ferrari
Journal: Hepatology (2005)

To characterize acute-phase hepatitis B virus (HBV)-specific T cell responses associated with self-limited and persistent HBV infections, we compared a patient with acute HBV/HCV coinfection, who was able to control HCV but developed chronic hepatitis B, with patients who resolved acute HBV infection spontaneously. Acute-phase CD4 responses were efficient in self-limited infections but undetectable in the coinfected patient with HBV persistence. CD8 responses were multispecific irrespective of the outcome of infection, but the CD8 repertoire associated with HBV persistence lacked the most dominant specificities detectable in self-limited infections. In conclusion, insufficient CD4 help and defective CD8 repertoire may play a role at the early stages of infection in influencing HBV persistence. (HEPATOLOGY 2005.)
Severity of silent myocardial ischemia on ambulatory electrocardiographic monitoring in patients with stable angina pectoris: Relation to prognostic determinants during exercise stress testing and coronary angiography
Authors: Freny Vaghaiwalla Mody, Koonlawee Nademanee, Vanida Intarachot, Martin A. Josephson, Helen A. Robertson, Bramah N. Singh
Journal: Journal of the American College of Cardiology (1988)
Is bivalirudin a safe alternative to heparin during carotid stenting? A case matched study
Authors: Yuliya G. Adamyan, Gishel New, Sriram Iyer, Thosaphol Limpijankit, Christina Brennan, Milena G. Adamian, Roxana Mehran, Izat Hjazi, Zoran Lasic, Sheriff Ibrahim, Jiri J. Vitek, Gary S. Roubin
Journal: Journal of the American College of Cardiology (2003)
Targeting Gonadotropin-releasing Hormone Receptor Inhibits the Early Step of Ovarian Cancer Metastasis by Modulating Tumor-mesothelial Adhesion
Authors: Lydia WT Cheung, Susan Yung, Tak-Mao Chan, Peter CK Leung, Alice ST Wong
Journal: Molecular Therapy (2012)

Ovarian cancer has a clear predilection to metastasize to the peritoneum, which represents one of the most important prognostic factors of poor clinical outcome. Gonadotropin-releasing hormone (GnRH) receptor is significantly overexpressed during the malignant progression of human ovarian cancer. Here, using lentiviral-based small interfering RNA (siRNA) technology to downregulate GnRH receptor in metastatic ovarian cancer cells, we show that GnRH receptor is an important mediator of ovarian cancer peritoneal metastasis. GnRH receptor downregulation dramatically attenuated their adhesion to the peritoneal mesothelium. By inhibiting the expression of GnRH receptor, we showed decreased expression of α2β1 and α5β1 integrin and adhesion to specific extracellular matrix (ECM) proteins. This was also associated with a reduction of P-cadherin. Furthermore, adhesion of ovarian cancer cells to different ECMs and the mesothelium were abrogated in response to β1 integrin and P-cadherin reduction, confirming that the effects were β1 integrin- and P-cadherin-specific. Using a mouse model of human ovarian cancer metastasis, we found that the inhibition of GnRH receptor, β1 integrin, and P-cadherin significantly attenuated tumor growth, ascites formation, and the number of metastatic implants. These results define a new role for GnRH receptor in early metastasis and offer the possibility of novel therapeutic targets.
PERSISTENCE AND UTILIZATION OF MATERNAL IRON FOR BLOOD FORMATION DURING INFANCY 12
Authors: Clement A. Smith, Ruth B. Cherry, Constantine J. Maletskos, John G. Gibson, Charles C. Roby, William L. Caton, Duncan E. Reid
Journal: Journal of Clinical Investigation (1955)

The concentration of hemoglobin in the blood of normal infants falls progressively during the first 4 to 6 weeks following birth.The decline results primarily from reduced hematopoiesis, though iron is present for the manufacture of hemoglobin and replacement of erythrocytes.The slow rise in hemoglobin concentration which occurs during the remainder of infancy may be affected by several factors, including the rapidity of body growth, the amount and absorption of dietary iron, and the amount and conservation of iron which was obtained transplacentally (1).An opportunity to measure the persistence and utilization of trans- placental iron during infancy arose as a by-product of investigations of maternal red cell volume and hematocrit recently published from this hospital (2, 3). MATERIAL AND METHODSIn the original studies (2, 3), radioactive iron (Fe) prepared in the Massachusetts Institute of Technology cyclotron was administered as donor red cells to 11 women on four to seven occasions during pregnancy.From these 11 pregnancies and from five subsequent ones of four of the women, a total of 16 infants were available for study.The mothers and their infants were similar in diet, hygiene and general health to the random population of any obstetrical hospital or well-baby clinic in this area.Figure 1 shows the hemoglobin concen- trations of the entire group of infants in comparison with controls from such clinics.1 Some of these data were reported at the Annual Meeting, American Pediatric Society, French Lick, Indiana, May 6, 1950.
Catheter-induced Urinary Infection: Follow-up Study
Authors: W. R. Cattell, M. P. Curwen, R. A. Shooter, D. K. Williams
Journal: BMJ (1963)

BRITMLJ _ 923M IA-JORA enable the relevance of spontaneous fibrinolysis to the problem of occlusive vascular disease to be tested by long-term therapeutic trial.Summary Blood fibrinolytic activity was compared by a single estimation in 50 male and 50 female diabetic out-patients, and in equal numbers of age-matched controls selected because of freedom from occlusive vascular disease.The diabetics as a group had lower fibrinolytic activity than the controls, and among the diabetics electrocardiographic evidence of myocardial ischaemia occurred twice as -commonly in those whose fibrinolytic activity was low as in those whose fibrinolytic activity was high.A significant inverse relationship between obesity and fibrinolytic activity was found in every group of patients except the female controls.There was no association between age and fibrinolytic activity, and among the diabetics no correlation between fibrinolytic activity and duration of diabetes, blood-sugar level, or cholesterol level.These observations suggest that spontaneous fibrino- lysis is of importance.If the function of fibrinolysis is to maintain vascular patency the possibility of enhancing its action pharmacologically may permit a fresh approach to the problem of occlusive vascular disease.
Pain Following Laceration
Authors: George R. Kraft
Journal: JAMA (1980)

<h3>To the Editor.—</h3> We would like further clarification of the discussion of "Reflex Sympathetic Dystrophy and Causalgia" (242:1790, 1979). There are problems in satisfactorily interpreting the data in this interesting case presentation as well as in understanding the labeling of the question and answer discussion. The patient described apparently had a laceration and later had persistent burning, pain, and discomfort in a median nerve distribution. One wonders why this case is being labeled reflex sympathetic dystrophy at all rather than being called just causalgia. There is no evidence in the presentation that the patient had reflex sympathetic dystrophy. There are difficulties accepting the electrodiagnosis data presented. It is stated that in June 1979, "the amplitude of the evoked potential was 2 μV," and the implication is that this figure refers to the compound muscle action potential. Such a small response, if obtained using surface electrodes, may well be indicative of
"CAN TYPHOID FEVER BE ABORTED?"A FEW ADDITIONAL CASES, THEIR PROGNOSIS AND TREATMENT. Read before the Mahoning County Medical Society, Feb. 12, 1894.
Authors: JOHN ELIOT WOODBRIDGE
Journal: JAMA (1894)

There is a strong probability that a large percent¬ age of all cases of insomnia in the insane can be re¬
Expression of Endogenous Oncogenic<i>V600EB-raf</i>Induces Proliferation and Developmental Defects in Mice and Transformation of Primary Fibroblasts
Authors: Kathryn Mercer, Susan Giblett, Stuart Green, David Lloyd, Silvy DaRocha Dias, Mark Plumb, Richard Marais, Catrin Pritchard
Journal: Cancer Research (2005)

Abstract Mutations of the human B-RAF gene are detected in ∼8% of cancer samples, primarily in cutaneous melanomas (70%). The most common mutation (90%) is a valine-to-glutamic acid mutation at residue 600 (V600E; formerly V599E according to previous nomenclature). Using a Cre/Lox approach, we have generated a conditional knock-in allele of V600EB-raf in mice. We show that widespread expression of V600EB-Raf cannot be tolerated in embryonic development, with embryos dying ∼7.5 dpc. Directed expression of mutant V600EB-Raf to somatic tissues using the IFN-inducible Mx1-Cre mouse strain induces a proliferative disorder and bone marrow failure with evidence of nonlymphoid neoplasia of the histiocytic type leading to death within 4 weeks of age. However, expression of mutant B-Raf does not alter the proliferation profile of all somatic tissues. In primary mouse embryonic fibroblasts, expression of endogenous V600EB-Raf induces morphologic transformation, increased cell proliferation, and loss of contact inhibition. Thus, V600EB-Raf is able to induce several hallmarks of transformation in some primary mouse cells without evidence for the involvement of a cooperating oncogene or tumor suppressor gene. (Cancer Res 2005; 65(24): 11493-500)
GOLF FROM A NEUROLOGICAL VIEWPOINT.
Authors: IRVING C. ROSSE
Journal: JAMA (1898)

Long before the Columbian rediscovery of America our hardy Caledonian ancestry amused themselves by playing the royal and ancient game which has been defined as the putting of little balls into little holes with instruments very ill adapted to the purpose. In those days certain ascetic and lugubrious persons, like the sham-pious reformers of the present, who condemn as sinful anything that makes people feel happy, cried down golf, football and other so- called unprofitable sports, which were prohibited by decree, the legislative blight being a canon of the old Scotch parliament against golf. Being difficult to extinguish strong instincts, people gave no heed to such prohibitions against the natural and wholesome promptings of the play impulse and manly pastimes of a vigorous race, and today we find a game with a long pedigree taken up and assimilated from Scotland, and so fascinating as to have spread
Influence of the extracellular matrix on fibroblast responsiveness to phenytoin using in vitro wound healing models
Authors: P.G. GENEVER, W.J. CUNLIFFE, E.J. WOOD
Journal: British Journal of Dermatology (1995)

Recent reports indicate that the topical administration of phenytoin to cutaneous wounds can promote repair. However, isolated skin cells (keratinocytes and flbroblasts) in vitro have varied in their response to phenytoin, giving rise to apparently contradictory results. We have examined how the structure of the extracellular matrix in which human dermal fibroblasts are grown in vitro can influence the response of these cells to phenytoin. The results indicate that, when fibroblasts are embedded within freely‐contracting, relaxed, type I collagen matrices, they are insensitive to phenytoin treatment. However, if fibroblasts are grown in collagen matrices which are non‐retracting and under tension, phenytoin (5–5μg/ml) significantly (P < 0.01) stimulates cell proliferation, and inhibits collagenase activity in a dose‐ and time‐dependent manner. The fact that the effects of phenytoin on dermal fibroblasts are biphasic and influenced by the surrounding matrix may help to explain why in vitro investigations with phenytoin give rise to inconsistent data. It also suggests that the matrix alterations which accompany wound healing may modulate the effects of phenytoin on dermal fibroblasts.
Coronary Artery Disease and Polymorphisms in a Receptor Mediating Shear Stress–Dependent Platelet Activation
Authors: Mitsuru Murata, Yumiko Matsubara, Koichi Kawano, Takeru Zama, Nobuo Aoki, Hideaki Yoshino, Gentaro Watanabe, Kyozo Ishikawa, Yasuo Ikeda
Journal: Circulation (1997)

Background Platelets play pivotal roles in coronary thrombosis, and antiplatelet therapies are widely used for coronary artery disease (CAD). However, the effects of genetic variation in platelets on CAD are poorly understood. We have assessed the association between CAD and polymorphisms in a platelet receptor for von Willebrand factor, the glycoprotein (GP) Ib/IX complex, which mediates shear stress–dependent platelet activation. Methods and Results Genotypes of the α-chain of the receptor (GP Ibα, 145 Thr/Met) were determined in 91 patients with myocardial infarction (MI) or angina pectoris whose lesions were confirmed by coronary angiography as well as in 105 individuals from the general population with no history of angina or other heart diseases and normal resting ECGs. There was no homozygote for Met/Met in either the control or patient groups. The prevalence of the Thr/Met genotype (T/M) in all patients was not significantly different from that in the control group. However, the frequency of T/M was significantly higher in patients aged ≤60 years (31.8%) than in control subjects aged ≤60 years (16.0%; P &lt;.05, odds ratio=2.5). An association was also demonstrated between CAD and the other polymorphism of GP Ibα, a variable number of tandem repeats of a 13–amino acid sequence, which is known to be linked to the 145 Thr/Met polymorphism. There was an association between the frequency of the T/M genotype and the angiographic severity of CAD: 11.1% for Gensini score &lt;40 versus 50.0% for Gensini score ≥40 ( P =.0015). There was no difference in the distribution of GP Ibα genotypes between patients with MI and those with angina pectoris. Conclusions This study suggests that the presence of the Met allele in GP Ibα is a risk factor for the prevalence and severity of CAD in individuals aged ≤60 years. The results need to be confirmed in a large-scale study of incident case subjects and matching control subjects.
Bone Scan Appearances in a Case of Ollier’s Disease
Authors: THOMAS GRÜNING, WOLF-GUNTER FRANKE
Journal: Clinical Nuclear Medicine (1999)

A 63-year-old woman had a large, hard tumor surrounding her left elbow joint. She reported that it had been growing slowly since the 1950s. The tumor was not painful, and there was only a slight restriction of movement. The bone scan showed involvement of the left side of the body, largely confined to the upper limb. Radiographs of the left arm showed multiple radiolucent lesions surrounding the elbow joint. A diagnosis of Ollier’s disease was made. This comprises enchondromatosis involving predominantly one side of the body. The bone scan clearly documents increased bone metabolism in Ollier’s disease.
Abstract 96: The functional role of DNA hypomethylation in liver cancer
Authors: Barbara Stefanska, Bishnu Bhattacharyya, Matthew Suderman, Jian Huang, Michael Hallett, Ze-Guang Han, Moshe Szyf
Journal: Cancer Research (2011)

Abstract DNA hypomethylation, a process of losing methyl marks, may play an important role in cancer, especially through activating genes that promote cancer metastasis, the deadly aspect of cancer. We previously delineated using whole genome promoter methylation microarrays the landscape of hypomethylation in hepatocellular carcinoma which is one of the most common cancers worldwide. Our studies revealed that 50% of differentially methylated promoters in tumors are hypomethylated compared to adjacent normal tissue. In the present studies, using liver cancer cell lines as a model system, we evaluated the importance of the identified hypomethylated genes in liver cancer development and progression. We tested whether the hypomethylation observed in liver cancer is driven by MBD2, a protein reported previously to be implicated in DNA demethylation, which we found to be overexpressed in liver cancer patients. Following siRNA MBD2 depletion in HepG2 hepatocellular carcinoma cell line, we used methylated DNA immunoprecipitation, chromatin immunoprecipitation (ChIP) and 60K custom microarrays covering 12K bp upstream and 10K bp downstream of transcription start site to determine methylation and MBD2 binding in 300 top genes hypomethylated and/or induced in liver cancer patients and/or HepG2 cells. The array data were validated by quantitative ChIP and/or pyrosequencing. For functional analyses, we used siRNA transfection, soft agar and invasion assays. We discovered MBD2 binding peaks in 172 genes out of 300, mainly within their promoter regions. Using bioinformatic tools, we identified MBD2 binding motif and established putative transcription factors recognizing this sequence which may play a key role in recruiting MBD2 to target genes. 41% of those genes were hypermethylated in HepG2 cells after MBD2 depletion in a fragment corresponding to MBD2 binding site. In addition, expression analysis for some of the genes showed attenuation. In HepG2 cells, we depleted expression of several of the genes hypomethylated in cancer and regulated by MBD2 using siRNA and demonstrated a decrease in cell growth and invasive capacities. Our results establish a role for MBD2 in coordinating inhibition of a panel of genes involved in cancer growth and metastasis. This study was supported by a grant from the MDEIE program of the government of Quebec and the National Cancer Institute of Canada to MS. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 96. doi:10.1158/1538-7445.AM2011-96
Forecasting Age-Related Macular Degeneration Through 2050
Authors: Barbara E. K. Klein
Journal: JAMA (2009)

David B. Rein, PhD; John S. Wittenborn, BS; Xinzhi Zhang, MD, PhD; Amanda A. Honeycutt, PhD; Sarah B. Lesesne, BS; Jinan Saaddine, MD, MPH; for the Vision Health Cost-Effectiveness Study GroupObjective: To forecast age-related macular degeneration (AMD) and its consequences in the United States through the year 2050 with different treatment scenarios.Methods: We simulated cases of early AMD, choroidal neovascularization (CNV), geographic atrophy (GA), and AMD-attributable visual impairment and blindness with 5 universal treatment scenarios: (1) no treatment; (2) focal laser and photodynamic therapy (PDT) for CNV; (3) vitamin prophylaxis at early-AMD incidence with focal laser/PDT for CNV; (4) no vitamin prophylaxis followed by focal laser treatment for extra and juxtafoveal CNV and anti–vascular endothelial growth factor treatment; and (5) vitamin prophylaxis at early-AMD incidence followed by CNV treatment, as in scenario 4.Results: Cases of early AMD increased from 9.1 million in 2010 to 17.8 million in 2050 across all scenarios. In non–vitamin-receiving scenarios, cases of CNV and GA increased from 1.7 million in 2010 to 3.8 million in 2050 (25% lower in vitamin-receiving scenarios). Cases of visual impairment and blindness increased from 620 000 in 2010 to 1.6 million in 2050 when given no treatment and were 2.4%, 22.0%, 16.9%, and 34.5% lower in scenarios 2, 3, 4, and 5, respectively.Conclusion: Prevalence of AMD will increase substantially by 2050, but the use of new therapies can mitigate its effects.
HCV-Associated B Cell Clonalities in the Liver Do Not Carry the t(14;18) Chromosomal Translocation *
Authors: Domenico Sansonno, Felicia Anna Tucci, Valli De Re, Gianfranco Lauletta, Michele Montrone, Massimo Libra, Franco Dammacco
Journal: Hepatology (2005)

Infection with HCV can be associated with B-cell non-Hodgkin lymphoma. Polymerase chain reaction (PCR) amplification assays for Bcl-2/IgH rearrangement were performed on nucleic acids extracted from portal tract inflammatory infiltrates, isolated with laser capture microdissection (LCM), from liver biopsy sections of 16 hepatitis C virus (HCV)-infected patients with and without extrahepatic B cell-related disorders. Results were compared with total DNA extracted from core liver biopsy specimens and from peripheral blood mononuclear cells (PBMCs). We failed to demonstrate specific Bcl-2/IgH amplicons either in liver tissue or in PBMCs in all patients of the current series. Multiple PCR assays for variable diversity joining (VDJ) IgH gene rearrangements were also performed in the liver compartment. Selective amplification compatible with mono or oligoclonal B cell clonotypes was demonstrated in 80% (6/8) and 25% (2/8) of patients with and without clinical evidence of B-cell disorders. V(H)1 and V(H)3 were the most represented V(H) families. In situ expression of Bcl-2 protein was carried out by immunohistochemistry on liver biopsy sections. Bcl-2 protein was detected in 2 (12.5%) patients who did not associate extrahepatic disorders. In conclusion, current data support the concept that production of IgH gene rearrangements is not associated with Bcl-2/IgH chromosomal translocation in hepatic compartment. Liver overexpression of Bcl-2 protein may occur in at least a minor proportion of HCV-infected patients.
Broad cellular immune response to CYP2D6 is restricted by HLA DR7 in patients with type 2 autoimmune hepatitis
Authors: Y. Ma, D.P. Bogdanos, J. Underhill, D. Arioli, S. Bansal, P. Cheeseman, G. Mieli-Vergani, D. Vergani
Journal: Journal of Hepatology (2003)
ATR–ATRIP Kinase Complex Triggers Activation of the Fanconi Anemia DNA Repair Pathway
Authors: Tomoko Shigechi, Junya Tomida, Koichi Sato, Masahiko Kobayashi, John K. Eykelenboom, Fabio Pessina, Yanbin Zhang, Emi Uchida, Masamichi Ishiai, Noel F. Lowndes, Kenichi Yamamoto, Hitoshi Kurumizaka, Yoshihiko Maehara, Minoru Takata
Journal: Cancer Research (2012)

Abstract ATR kinase activates the S-phase checkpoint when replication forks stall at sites of DNA damage. This event also causes phosphorylation of the Fanconi anemia (FA) protein FANCI, triggering its monoubiquitination of the key DNA repair factor FANCD2 by the FA core E3 ligase complex, thereby promoting this central pathway of DNA repair which permits replication to be restarted. However, the interplay between ATR and the FA pathway has been unclear. In this study, we present evidence that their action is directly linked, gaining insights into this relationship in a DT40 mutant cell line that is conditionally deficient in the critical ATR-binding partner protein ATRIP. Using this system, we showed that ATRIP was crucial for DNA damage–induced FANCD2 monoubiquitination and FANCI phosphorylation. ATR kinase phosphorylated recombinant FANCI protein in vitro, which was facilitated by the presence of FANCD2. Mechanistic investigations revealed that the RPA region but not the TopBP1 region of ATRIP was required for FANCD2 monoubiquitination, whereas Chk1 phosphorylation relied upon both domains. Together, our findings identify ATR as the kinase responsible for activating the FA pathway of DNA repair. Cancer Res; 72(5); 1149–56. ©2012 AACR.