tbuckley/cabot-search huggingface dataset:
A Novel Approach to Investigation of the Pathogenesis of Active Minimal-Change Nephrotic Syndrome Using Subtracted cDNA Library Screening
Authors: Djillali Sahali, André Pawlak, Asta Valanciuté, Philippe Grimbert, Philippe Lang, Philippe Remy, Albert Bensman, Georges Guelle[Combining Diaeresis]n
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Clinical and experimental observations suggest that minimal-change nephrotic syndrome (MCNS) results from T cell dysfunction, via unknown mechanisms. For the identification of genes that are potentially involved in MCNS, a subtractive cDNA library was constructed from cDNA from T cell-enriched peripheral blood mononuclear cells obtained from the same patient during relapse versus remission (“relapse minus remission”). This library was screened by differential hybridization with forward (“relapse minus remission”) and reverse (“remission minus relapse”) subtractive cDNAs probes, as well as unsubtracted probes from relapse and remission, and irrelevant nephrotic syndrome (membranous nephropathy). A total of 84 transcripts were isolated, of which 12 matched proteins of unknown function and 30 were unknown clones. Among the 42 known transcripts, at least 18 are closely involved in the T cell receptor-mediated complex signaling cascade, including genes encoding components of the T cell receptor and proteins associated with the cytoskeletal scaffold, as well as transcription factors. In particular, it was demonstrated that the expression levels of Fyb/Slap, L-plastin, and grancalcin were increased during relapse, suggesting that the integration of proximal signaling after T cell engagement involves the preferential recruitment of these cytoskeleton-associated proteins in MCNS. Because very low levels of interleukin-12 receptor β2 mRNA were detected in relapse samples, the interleukin-12 signaling pathway might be defective, suggesting that, in MCNS, T cell activation evolves toward a T helper 2 phenotype. Therefore, the combination of subtractive cloning and differential screening constitutes an efficient approach to the identification of genes that are likely to be involved in the pathophysiologic processes of MCNS.
E-motions: Email for Written Emotional Expression
Authors: Florian Strasser, Michael Fisch, Diane C. Bodurka, Debra Sivesind, Eduardo Bruera
Journal: Journal of Clinical Oncology (2002)

Article Tools THE ART OF ONCOLOGY: WHEN THE TUMOR IS NOT THE TARGET Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.15.3352 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12149311 E-motions: Email for Written Emotional Expression Florian StrasserxFlorian StrasserSearch for articles by this author , Michael FischxMichael FischSearch for articles by this author , Diane C. BodurkaxDiane C. BodurkaSearch for articles by this author , Debra SivesindxDebra SivesindSearch for articles by this author , Eduardo BrueraxEduardo BrueraSearch for articles by this author Show More From the Department of Palliative Care and Rehabilitation Medicine and Department of Gynecologic Oncology, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX. https://doi.org/10.1200/JCO.2002.20.15.3352 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Randomized Comparison of Strategies for Type B Aortic Dissection
Authors: Christoph A. Nienaber, Hervé Rousseau, Holger Eggebrecht, Stephan Kische, Rossella Fattori, Tim C. Rehders, Günther Kundt, Dierk Scheinert, Martin Czerny, Tilo Kleinfeldt, Burkhart Zipfel, Louis Labrousse, Hüseyin Ince
Journal: Circulation (2009)

Thoracic endovascular aortic repair (TEVAR) represents a novel concept for type B aortic dissection. Although life-saving in acute emergencies, outcomes and survival of TEVAR in stable dissection are unknown.One hundred forty patients in stable clinical condition at least 2 weeks after index dissection were randomly subjected to elective stent-graft placement in addition to optimal medical therapy (n=72) or to optimal medical therapy alone (n=68) with surveillance (arterial pressure according to World Health Organization guidelines < or =120/80 mm Hg). The primary end point was all-cause death at 2 years, whereas aorta-related death, progression (with need for conversion or additional endovascular or open surgery), and aortic remodeling were secondary end points. There was no difference in all-cause deaths, with a 2-year cumulative survival rate of 95.6+/-2.5% with optimal medical therapy versus 88.9+/-3.7% with TEVAR (P=0.15); the trial, however, turned out to be underpowered. Moreover, the aorta-related death rate was not different (P=0.44), and the risk for the combined end point of aorta-related death (rupture) and progression (including conversion or additional endovascular or open surgery) was similar (P=0.65). Three neurological adverse events occurred in the TEVAR group (1 paraplegia, 1 stroke, and 1 transient paraparesis), versus 1 case of paraparesis with medical treatment. Finally, aortic remodeling (with true-lumen recovery and thoracic false-lumen thrombosis) occurred in 91.3% of patients with TEVAR versus 19.4% of those who received medical treatment (P<0.001), which suggests ongoing aortic remodeling.In the first randomized study on elective stent-graft placement in survivors of uncomplicated type B aortic dissection, TEVAR failed to improve 2-year survival and adverse event rates despite favorable aortic remodeling.
Molecular Lymph Node Staging in Bladder Urothelial Carcinoma: Impact on Survival
Authors: Mercedes Marín-Aguilera, Lourdes Mengual, Moisès Burset, Artur Oliver, Elisabet Ars, María José Ribal, Dolors Colomer, Begoña Mellado, Humberto Villavicencio, Ferran Algaba, Antonio Alcaraz
Journal: European Urology (2008)
Tubal Ligation, Hysterectomy, and Risk of Ovarian Cancer
Authors: S. Elizabeth Whitmore
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Dr Hankinson and colleagues<sup>1</sup>report an inverse relationship between tubal ligation and ovarian cancer and propose mechanisms for a possible causal association that involve altered ovulatory cycles and gonadotropin, estrogen, and progesterone levels. They conclude that it "may be appropriate to consider the reduced risk of ovarian cancer when choosing among alternative methods of contraception." Their findings, which corroborate several studies, are interesting and important. However, it is imperative to question how tubal ligation may alter normal physiology of premenopausal women and what long-term effects it may have on accelerating two conditions which eventually occur in virtually all women, osteoporosis and atherosclerosis. In this context, the effects of ovulation and estrogen and progesterone levels on bone density and lipid levels should be considered. Concerning bone density, it has been shown that even asymptomatic ovulatory disturbances may be associated with decreased spinal density.<sup>2</sup>With regard to
Aberrant Nuclear Accumulation of Glycogen Synthase Kinase-3β in Human Pancreatic Cancer: Association with Kinase Activity and Tumor Dedifferentiation
Authors: Andrei V. Ougolkov, Martin E. Fernandez-Zapico, Vladimir N. Bilim, Thomas C. Smyrk, Suresh T. Chari, Daniel D. Billadeau
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We have shown recently that glycogen synthase kinase-3 (GSK-3) β regulates nuclear factor-κB (NF-κB)–mediated pancreatic cancer cell survival and proliferation in vitro. Our objective was to determine the localization of GSK-3β in pancreatic cancer cells and assess the antitumor effect of GSK-3 inhibition in vivo to improve our understanding of the mechanism by which GSK-3β affects NF-κB activity in pancreatic cancer. Experimental Design: Immunohistochemistry and cytosolic/nuclear fractionation were done to determine the localization of GSK-3β in human pancreatic tumors. We studied the effect of GSK-3 inhibition on tumor growth, cancer cell proliferation, and survival in established CAPAN2 tumor xenografts using a tumor regrowth delay assay, Western blotting, bromodeoxyuridine incorporation, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling. Results: We found nuclear accumulation of GSK-3β in pancreatic cancer cell lines and in 62 of 122 (51%) human pancreatic adenocarcinomas. GSK-3β nuclear accumulation is significantly correlated with human pancreatic cancer dedifferentiation. We have found that active GSK-3β can accumulate in the nucleus of pancreatic cancer cells and that inhibition of GSK-3 kinase activity represses its nuclear accumulation via proteasomal degradation within the nucleus. Lastly, we have found that inhibition of GSK-3 arrests pancreatic tumor growth in vivo and decreases NF-κB-mediated pancreatic cancer cell survival and proliferation in established tumor xenografts. Conclusions: Our results show the antitumor effect of GSK-3 inhibition in vivo, identify GSK-3β nuclear accumulation as a hallmark of poorly differentiated pancreatic adenocarcinoma, and provide new insight into the mechanism by which GSK-3β regulates NF-κB activity in pancreatic cancer.
Combination of Sulindac and Antimicrobial Eradication of <i>Helicobacter pylori</i> Prevents Progression of Gastric Cancer in Hypergastrinemic INS-GAS Mice
Authors: Chung-Wei Lee, Barry Rickman, Arlin B. Rogers, Sureshkumar Muthupalani, Shigeo Takaishi, Peiying Yang, Timothy C. Wang, James G. Fox
Journal: Cancer Research (2009)

Helicobacter pylori infection causes severe dysplasia manifested as gastrointestinal intraepithelial neoplasia (GIN) after 28 weeks post-H. pylori infection (WPI) in cancer-prone, hypergastrinemic male INS-GAS mice. We examined the efficacy of the nonsteroidal anti-inflammatory drug sulindac (400 ppm in drinking water) alone, the CCK2/gastrin receptor antagonist YM022 (45 mg/kg/wk) alone, and sulindac or YM022 combined with H. pylori eradication therapy to prevent H. pylori-associated gastric cancer in male INS-GAS mice. Treatments started at 22 WPI, and mice were euthanized at 28 WPI. In uninfected mice, all treatments significantly delayed development of spontaneous GIN (P < 0.05). In H. pylori-infected mice, sulindac alone or YM022 alone had no protective effect on H. pylori-associated GIN. Importantly, sulindac exacerbated the severity of H. pylori-associated gastritis despite decreased gastric prostaglandin E(2) levels. However, sulindac combined with H. pylori antimicrobial eradication reduced the incidence of GIN (P < 0.05), whereas YM022 combined with antimicrobial eradication did not reduce GIN. In infected mice, sulindac or YM022 treatment did not alter gastric expression of the proinflammatory cytokines Ifn-gamma and Tnf-alpha and mucosal cell proliferation. Sulindac or YM022 combined with antimicrobial eradication down-regulated mRNA levels of Ifn-gamma and Tnf-alpha and mucosal cell proliferation (P < 0.05). We conclude that sulindac enhances H. pylori gastritis and may promote inflammation-mediated gastric carcinogenesis. The combination of sulindac and antimicrobial H. pylori eradication was beneficial for reducing proinflammatory cytokine mRNA in the stomach and preventing progression from severe dysplasia to gastric cancer in H. pylori-infected INS-GAS mice.
Pharmacoproteomics identifies combinatorial therapy targets for diffuse large B cell lymphoma
Authors: Rebecca L. Goldstein, Shao Ning Yang, Tony Taldone, Betty Chang, John Gerecitano, Kojo Elenitoba-Johnson, Rita Shaknovich, Wayne Tam, John P. Leonard, Gabriela Chiosis, Leandro Cerchietti, Ari Melnick
Journal: Journal of Clinical Investigation (2015)

Rationally designed combinations of targeted therapies for refractory cancers, such as activated B cell-like diffuse large B cell lymphoma (ABC DLBCL), are likely required to achieve potent, durable responses. Here, we used a pharmacoproteomics approach to map the interactome of a tumor-enriched isoform of HSP90 (teHSP90). Specifically, we chemically precipitated teHSP90-client complexes from DLBCL cell lines with the small molecule PU-H71 and found that components of the proximal B cell receptor (BCR) signalosome were enriched within teHSP90 complexes. Functional assays revealed that teHSP90 facilitates BCR signaling dynamics by enabling phosphorylation of key BCR signalosome components, including the kinases SYK and BTK. Consequently, treatment of BCR-dependent ABC DLBCL cells with PU-H71 attenuated BCR signaling, calcium flux, and NF-κB signaling, ultimately leading to growth arrest. Combined exposure of ABC DLBCL cell lines to PU-H71 and ibrutinib, a BCR pathway inhibitor, more potently suppressed BCR signaling than either drug alone. Correspondingly, PU-H71 combined with ibrutinib induced synergistic killing of lymphoma cell lines, primary human lymphoma specimens ex vivo, and lymphoma xenografts in vivo, without notable toxicity. Together, our results demonstrate that a pharmacoproteome-driven rational combination therapy has potential to provide more potent BCR-directed therapy for ABC DLCBL patients.
Nitric oxide localized to spinal cords of mice with experimental allergic encephalomyelitis: an electron paramagnetic resonance study.
Authors: R F Lin, T S Lin, R G Tilton, A H Cross
Journal: The Journal of Experimental Medicine (1993)

Experimental allergic encephalomyelitis (EAE) is a demyelinating autoimmune disorder that can be induced in susceptible mice by T lymphocytes sensitized to central nervous system (CNS) myelin components and is a prime animal model for the human CNS demyelinating disorder, multiple sclerosis (MS). Although CNS inflammation in which T lymphocytes and activated macrophages are the predominant cell types is observed in mice with EAE and in humans with MS, the exact mechanisms underlying the CNS damage and demyelination are not understood. Nitric oxide (NO), a gaseous free radical, has recently been shown to be a cytolytic product of activated macrophages. Using electron paramagnetic resonance spectroscopy, the nitric oxide free radical complexed with iron-sulfur proteins has been identified in affected spinal cords of mice with EAE, concurrent with the diminution of iron-sulfur proteins. These results indicate NO may play a role in the disease process of EAE, and perhaps MS.
Gene Panel Model Predictive of Outcome in Men at High-Risk of Systemic Progression and Death From Prostate Cancer After Radical Retropubic Prostatectomy
Authors: John C. Cheville, R. Jeffrey Karnes, Terry M. Therneau, Farhad Kosari, Jan-Marie Munz, Lori Tillmans, Eati Basal, Laureano J. Rangel, Eric Bergstralh, Irina V. Kovtun, C.D. Savci-Heijink, Eric W. Klee, George Vasmatzis
Journal: Journal of Clinical Oncology (2008)

Purpose In men who are at high-risk of prostate cancer, progression and death from cancer after radical retropubic prostatectomy (RRP), limited prognostic information is provided by established prognostic features. The objective of this study was to develop a model predictive of outcome in this group of patients. Methods Candidate genes were identified from microarray expression data from 102 laser capture microdissected prostate tissue samples. Candidates were overexpressed in tumor compared with normal prostate and more frequently in Gleason patterns 4 and 5 than in 3. A case control study of 157 high-risk patients, matched on Gleason score and stage with systemic progression or death of prostate cancer as the end point, was used to evaluate the expression of candidate genes and build a multivariate model. Tumor was collected from the highest Gleason score in paraffin-embedded blocks and the gene expression was quantified by real-time reverse transcription polymerase chain reaction. Validation of the final model was performed on a separate case-control study of 57 high-risk patients who underwent RRP. Results A model incorporating gene expression of topoisomerase-2a, cadherin-10, the fusion status based on ERG, ETV1, and ETV4 expression, and the aneuploidy status resulted in a 0.81 area under the curve (AUC) in receiver operating characteristic statistical analysis for the identification of men with systemic progression and death from high grade prostate cancer. The AUC was 0.79 in the independent validation study. Conclusion The model can identify men with high-risk prostate cancer who may benefit from more intensive postoperative follow-up and adjuvant therapies.
Requirement for the Chemokine Receptor Ccr6 in Allergic Pulmonary Inflammation
Authors: Nicholas W. Lukacs, Dina M. Prosser, Maria Wiekowski, Sergio A. Lira, Donald N. Cook
Journal: The Journal of Experimental Medicine (2001)

Allergic asthmatic responses in the airway are associated with airway hyperreactivity, eosinophil accumulation in the lung, and cytokine production by allergen-specific, T helper cell type 2 (Th2) lymphocytes. Here, we show that in a cockroach antigen (CA) model of allergic pulmonary inflammation, the chemokine macrophage inflammatory protein (MIP)-3α is expressed in the lung within hours of allergen challenge. To determine the biologic relevance of this expression, mice lacking CCR6, the only known receptor for MIP-3α, were studied for their response to CA. CCR6-deficient mice were immunized to the same extent as their wild-type counterparts, as judged by cytokine production in antigen-challenged lymphocytes. However, compared with CA-challenged wild-type mice, challenged CCR6-deficient mice had reduced airway resistance, fewer eosinophils around the airway, lower levels of interleukin 5 in the lung, and reduced serum levels of immunoglobulin E. Together, these data demonstrate that MIP-3α and CCR6 function in allergic pulmonary responses and suggest that these molecules might represent novel therapeutic targets for treatment of asthma.
Double outlet right ventricle: clinical and anatomical spectrum.
Authors: E K Weir, H S Joffe, C N Barnard, W Beck
Journal: Thorax (1978)

Thirty-two patients with double outlet right ventricle (DORV) were studied between 1960 and 1976. Associated congenital defects frequently compounded the difficulty of clinical diagnosis. Cardiac catheterisation was performed in 27 patients, and the ventriculograms were studied with particular regard to the relative positions of the great vessels to each other and to the ventricular septal defect. These relationships determine which corrective operation is possible. Correction has been performed in 12 patients with a perioperative mortality of 25%. Although mitral-aortic discontinuity was demonstrated in all cases, consideration of the anatomical spectrum included in the term DORV suggests that discontinuity is not an essential feature. In common with other clinical data and in contrast with necropsy studies, none of our patients was found to show the normal relationship of the great vessels to each other, in which the aorta lies posterior and to the right of the pulmonary artery. The reason for this difference between the clinical and necropsy findings is not apparent. A similar disparity was shown with regard to pulmonary stenosis, which was demonstrated at catheterisation in 68% of the 27 patients (mean gradient 68 +/- 3 mmHg), in contrast with incidences of 18% and 25% in recent necropsy series. Patients in the necropsy studies were frequently neonates or infants, in whom death may have been the result of intractable cardiac failure secondary to excessive pulmonary blood flow. In older patients without pulmonary stenosis and with pulmonary hypertension, frequent observation is imperative so that surgical treatment can be instituted before the development of irreversible pulmonary vascular disease.
Quadrivalent Vaccine against Human Papillomavirus to Prevent Anogenital Diseases
Authors: Suzanne M. Garland, Mauricio Hernandez-Avila, Cosette M. Wheeler, Gonzalo Perez, Diane M. Harper, Sepp Leodolter, Grace W.K. Tang, Daron G. Ferris, Marc Steben, Janine Bryan, Frank J. Taddeo, Radha Railkar, Mark T. Esser, Heather L. Sings, Micki Nelson, John Boslego, Carlos Sattler, Eliav Barr, Laura A. Koutsky
Journal: New England Journal of Medicine (2007)

A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus (HPV) types 6, 11, 16, and 18.In this randomized, placebo-controlled, double-blind trial involving 5455 women between the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1, month 2, and month 6. The coprimary composite end points were the incidence of genital warts, vulvar or vaginal intraepithelial neoplasia, or cancer and the incidence of cervical intraepithelial neoplasia, adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data for the primary analysis were collected for a per-protocol susceptible population of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1 month after administration of the third dose.The women were followed for an average of 3 years after administration of the first dose. In the per-protocol population, those followed for vulvar, vaginal, or perianal disease included 2261 women (83%) in the vaccine group and 2279 (83%) in the placebo group. Those followed for cervical disease included 2241 women (82%) in the vaccine group and 2258 (83%) in the placebo group. Vaccine efficacy was 100% for each of the coprimary end points. In an intention-to-treat analysis, including those with prevalent infection or disease caused by vaccine-type and non-vaccine-type HPV, vaccination reduced the rate of any vulvar or vaginal perianal lesions regardless of the causal HPV type by 34% (95% confidence interval [CI], 15 to 49), and the rate of cervical lesions regardless of the causal HPV type by 20% (95% CI, 8 to 31).The quadrivalent vaccine significantly reduced the incidence of HPV-associated anogenital diseases in young women. (ClinicalTrials.gov number, NCT00092521 [ClinicalTrials.gov].).
Re: Age-Specific Evaluation of Primary Human Papillomavirus Screening vs Conventional Cytology in a Randomized Setting
Authors: Elsebeth Lynge, Matejka Rebolj
Journal: JNCI Journal of the National Cancer Institute (2010)

Leinonen et al. (1) recently reported results for women aged 25–65 years from the base line round of cervical screening in a Finnish randomized controlled trial that compared human papillomavirus (HPV) DNA screening with conventional cytology screening. The authors reported that HPV DNA screening combined with cytology triage had a specificity of 98.9% for cer vical intraepithelial neoplasia grade 3 or higher (CIN 3+; number of women with a negative screening test divided by total number of women screened minus the number with histologically confirmed CIN 3+). The same specificity was found for conventional cytology screening. In calcu lating these specificities, all women without a direct referral for colposcopy, that is, those with a less severe abnormality than low-grade squamous intraepithelial lesion on cytology, were considered screen nega tive. In this case, it is hardly surprising that the two screening methods appeared to have the same specificity, given that only a small proportion of low-grade squamous intraepithelial lesions or more severe ab
LIGATURE OF INNOMINATE AND COMMON CAROTID ARTERIES FOR SUBCLAVIAN ANEURYSM
Authors: C. L. G. Chapman
Journal: BMJ (1929)

TwNB7 B 49 applied to the hole in the end of the halonieter.The halo diameter and the date are recorded oin the label of the slide, and kept so that the progress on liver diet mnay be noted.Most red cells preserve their si7e indefinlitely, !hutI tllinik that where the plasma is relatively, abundant (as in sever'e peinicious anaemiiia) the red, cells must be very slowil stretelc-d ii the course af weeks hy shlinking of the plnssia filmii; so it is well to measuire. (or post) the film without manyv (clays' delay.I do niot heat the films.PRE-PERNIcIOUS ANAEMI.OUtI formler coneeptions of pernicious anaemlia apply only to the late stages; the ear ly stages are quite different.Entlar gement of the red cells is the first reliable sign;