tbuckley/cabot-search huggingface dataset:
Positive Cross-Regulatory Loop Ties GATA-3 to Estrogen Receptor α Expression in Breast Cancer
Authors: Jérôme Eeckhoute, Erika Krasnickas Keeton, Mathieu Lupien, Susan A. Krum, Jason S. Carroll, Myles Brown
Journal: Cancer Research (2007)

Abstract The transcription factor GATA-3 is required for normal mammary gland development, and its expression is highly correlated with estrogen receptor α (ERα) in human breast tumors. However, the functional role of GATA-3 in ERα-positive breast cancers is yet to be established. Here, we show that GATA-3 is required for estradiol stimulation of cell cycle progression in breast cancer cells. The role of GATA-3 in estradiol signaling requires the direct positive regulation of the expression of the ERα gene itself by GATA-3. GATA-3 binds to two cis-regulatory elements located within the ERα gene, and this is required for RNA polymerase II recruitment to ERα promoters. Reciprocally, ERα directly stimulates the transcription of the GATA-3 gene, indicating that these two factors are involved in a positive cross-regulatory loop. Moreover, GATA-3 and ERα regulate their own expression in breast cancer cells. Hence, this transcriptional coregulatory mechanism accounts for the robust coexpression of GATA-3 and ERα in human breast cancers. In addition, these results highlight the crucial role of GATA-3 for the response of ERα-positive breast cancers to estradiol. Moreover, they identify GATA-3 as a critical component of the master cell-type–specific transcriptional network including ERα and FoxA1 that dictates the phenotype of hormone-dependent breast cancer. [Cancer Res 2007;67(13):6477–83]
Inguinal Hernia After Radical Prostatectomy for Prostate Cancer: Results From a Randomized Setting and a Nonrandomized Setting
Authors: Johan Stranne, Eva Johansson, Andreas Nilsson, Anna Bill-Axelson, Stefan Carlsson, Lars Holmberg, Jan-Erik Johansson, Tommy Nyberg, Mirja Ruutu, N. Peter Wiklund, Gunnar Steineck
Journal: European Urology (2010)
Did Publication of a Clinical Practice Guideline Recommendation to Screen for Type 2 Diabetes in Women With Gestational Diabetes Change Practice?
Authors: Heather D. Clark, Carl van Walraven, Cathy Code, Alan Karovitch, Erin Keely
Journal: Diabetes Care (2003)

OBJECTIVE—To determine whether women with previous gestational diabetes mellitus (GDM) were screened postpartum for type 2 diabetes according to the Canadian Diabetes Association (CDA) guidelines. RESEARCH DESIGN AND METHODS—The 1998 CDA guidelines recommend that all women diagnosed with GDM be screened postpartum for type 2 diabetes using a 2-h 75-g oral glucose tolerance test (OGTT). The impact of and compliance with this expert opinion-based recommendation is unknown. All women who delivered at the Ottawa Hospital in 1997 (pre-guideline) and 2000 (post-guideline) with confirmed GDM were identified. Using population-based administrative databases, we determined the proportion of these women who had an OGTT, serum glucose test, or glycated hemoglobin (GHb) test in the first postpartum year. Women who had not undergone any blood work were excluded. RESULTS—There were 131 women in 1997 and 123 women in 2000 with confirmed GDM. Of these, only 69 women in 1997 and 52 women in 2000 had blood work recorded in the database. None of these women had an OGTT performed in either period. We found a significant increase in the measurement of serum glucose (50 women pre-guideline [72.1%], 48 women post-guideline [92.3%], P &amp;lt; 0.05) and GHb (8 women pre-guideline [11.6%], 20 women post-guideline [38.5%], P &amp;lt; 0.01). CONCLUSIONS—In our region, physicians are not following the CDA recommendations to screen women with GDM postpartum with an OGTT. However, we did find a significant increase in the measurement of serum glucose and GHb. Publication of expert opinion-based guidelines did not change the postpartum use of an OGTT in these women but may have increased the use of less reliable screening tests for type 2 diabetes.
Rheumatoid Factor as a Potentiator of Anti–Citrullinated Protein Antibody–Mediated Inflammation in Rheumatoid Arthritis
Authors: Jeremy Sokolove, Dannette S. Johnson, Lauren J. Lahey, Catriona A. Wagner, Danye Cheng, Geoffrey M. Thiele, Kaleb Michaud, Harlan Sayles, Andreas M. Reimold, Liron Caplan, Grant W. Cannon, Gail Kerr, Ted R. Mikuls, William H. Robinson
Journal: Arthritis & Rheumatology (2014)

The co-occurrence of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA-associated inflammation.In a cohort of 1,488 US veterans with RA, measures of disease activity and serum levels of cytokines and multiplex ACPAs were compared between the following groups of patients: double-negative (anti-cyclic citrullinated peptide [anti-CCP]-/RF-), anti-CCP+/RF-, anti-CCP-/RF+, or double-positive (anti-CCP+/RF+). Additional studies were performed using an in vitro immune complex (IC) stimulation assay in which macrophages were incubated with ACPA ICs in the presence or absence of monoclonal IgM-RF, and tumor necrosis factor α production measured as a readout of macrophage activation.Compared with the double-negative subgroup (as well as each single-positive subgroup), the double-positive subgroup exhibited higher disease activity as well as higher levels of C-reactive protein and inflammatory cytokines (all P < 0.001). In vitro stimulation of macrophages by ACPA ICs increased cytokine production, and the addition of monoclonal IgM-RF significantly increased macrophage tumor necrosis factor α production (P = 0.003 versus ACPA ICs alone).The combined presence of ACPAs and IgM-RF mediates increased proinflammatory cytokine production in vitro and is associated with increased systemic inflammation and disease activity in RA. Our data suggest that IgM-RF enhances the capacity of ACPA ICs to stimulate macrophage cytokine production, thereby providing a mechanistic link by which RF enhances the pathogenicity of ACPA ICs in RA.
Intrathoracic Mass in a Young Woman With Skin Lesions
Authors: Jahanguir Yaghoobian
Journal: JAMA (1979)

<h3>History</h3> A 31-year-old woman was hospitalized for further evaluation of a mass that was discovered on a chest roentgenogram taken because of an upper respiratory tract infection. Physical examination revealed several café-aulait spots over the skin. Kyphoscoliosis of the midthoracic vertebrae with posterior scalloping of some of the vertebral bodies was also noted. The admission posteroanterior chest film is shown in Fig 1. A well-defined left paravertebral soft-tissue mass density measured about 6 cm in diameter. Figure 2 is an anteroposterior tomogram of the dorsal spine. <h3>Diagnosis</h3> Lateral intrathoracic meningocele in a patient with neurofibromatosis. Figures 1 and 2 show a large left paravertebral mass with scalloping of the left side of the bodies of D7 to D9. The possibility of neurofibromatosis with an intrathoracic meningocele was suspected from the patient's physical examination and roentgen findings. This was confirmed by myelography (Fig 3), which showed contrast material filling the masslike
Insulin resistance in limb and trunk partial lipodystrophy (type 2 Köbberling-Dunnigan syndrome)
Authors: Mileni J.M. Ursich, Rosa T. Fukui, Maria S.A. Galvão, Jose A.M. Marcondes, Ana T.M.G. Santomauro, Maria E.R. Silva, Dalva M. Rocha, Bernardo L. Wajchenberg
Journal: Metabolism (1997)
Immune Parameters Correlate with Protection Against Ebola Virus Infection in Rodents and Nonhuman Primates
Authors: Gary Wong, Jason S. Richardson, Stéphane Pillet, Ami Patel, Xiangguo Qiu, Judie Alimonti, Jeff Hogan, Yi Zhang, Ayato Takada, Heinz Feldmann, Gary P. Kobinger
Journal: Science Translational Medicine (2012)

Levels of specific antibodies induced by vaccination correlate with survival in Ebola-infected animals.
A Phylogenetic Analysis of 34 Chloroplast Genomes Elucidates the Relationships between Wild and Domestic Species within the Genus<i>Citrus</i>
Authors: Jose Carbonell-Caballero, Roberto Alonso, Victoria Ibañez, Javier Terol, Manuel Talon, Joaquin Dopazo
Journal: Molecular Biology and Evolution (2015)

Citrus genus includes some of the most important cultivated fruit trees worldwide. Despite being extensively studied because of its commercial relevance, the origin of cultivated citrus species and the history of its domestication still remain an open question. Here, we present a phylogenetic analysis of the chloroplast genomes of 34 citrus genotypes which constitutes the most comprehensive and detailed study to date on the evolution and variability of the genus Citrus. A statistical model was used to estimate divergence times between the major citrus groups. Additionally, a complete map of the variability across the genome of different citrus species was produced, including single nucleotide variants, heteroplasmic positions, indels (insertions and deletions), and large structural variants. The distribution of all these variants provided further independent support to the phylogeny obtained. An unexpected finding was the high level of heteroplasmy found in several of the analyzed genomes. The use of the complete chloroplast DNA not only paves the way for a better understanding of the phylogenetic relationships within the Citrus genus but also provides original insights into other elusive evolutionary processes, such as chloroplast inheritance, heteroplasmy, and gene selection.
Influence of Tamoxifen on Carotid Intima-Media Thickness in Postmenopausal Women
Authors: T. Simon, P. Boutouyrie, J.M. Simon, B. Laloux, C. Tournigand, A.I. Tropeano, S. Laurent, P. Jaillon
Journal: Circulation (2002)

Intima-media thickness of the common carotid artery (IMT-CCA) is an early marker of atherosclerosis. Tamoxifen is a selective estrogen-receptor modulator with estrogen-like effects on cardiovascular risk factors but as-yet unexplored effects on carotid artery structure. The goal of this study was to determine the influence of tamoxifen on IMT-CCA in menopausal women.With a predefined calculation of the sample size, 67 menopausal women with cancer who were treated with tamoxifen for > or =1 year and 37 menopausal women with cancer who were never treated with tamoxifen were enrolled. IMT-CCA, internal diameter, and pulse pressure were determined with a high-definition echotracking device and applanation tonometry in a central core laboratory that was blinded to treatment. Both groups were similar for clinical characteristics, including cardiovascular risk factors. IMT and internal diameter were significantly lower in the tamoxifen group (mean duration of treatment, 2.4+/-0.9 years) than in the control group (609+/-117 microm versus 662+/-147 microm, P=0.04, and 4.89+/-0.60 mm versus 5.12+/-0.58 mm, P=0.03, respectively). Pulse pressure was not influenced by the use of tamoxifen. After adjustment for age, cardiovascular risk factors, carotid pulse pressure, duration of menopause, and previous use of hormone replacement therapy, IMT remained significantly lower among tamoxifen users (P<0.00001), with an impact on IMT (-70 microm) equivalent to spontaneous evolution with 12 years of aging (5 microm/y).The use of tamoxifen was associated with a significantly lower carotid IMT in menopausal women with cancer. Randomized trials are needed to confirm the cardioprotective effect of selective estrogen-receptor modulators in terms of prevention of atherosclerosis.
Development of a prognostic index for 90-day mortality in patients discharged after admission to hospital for community-acquired pneumonia
Authors: A Capelastegui, P P Espana, J M Quintana, A Bilbao, R Menendez, R Zalacain, A Torres
Journal: Thorax (2009)

<h3>Background:</h3> Although patients admitted to hospital for community-acquired pneumonia (CAP) experience substantial short-term mortality following hospital discharge, few studies have focused on identifying factors that predict mortality after admission to hospital in this population. The objective of this study was to develop and validate a prognostic index for 90-day mortality after hospital discharge among patients with CAP. <h3>Methods:</h3> The prognostic index was derived in 1117 adult patients discharged between 2003 and 2007 from a general hospital following admission for CAP. It was validated in 646 consecutive patients with CAP discharged from three other hospitals between 1 November 2005 and 31 July 2006. Risk factors evaluated included host-related factors, severity upon admission, in-hospital management and bacteriology. <h3>Results:</h3> In the derivation cohort, three factors were independently associated with 90-day mortality: pre-illness functional status, Charlson index (composite measure of co-morbid illnesses) and severity on admission. Mortality at 90 days was 0.7% in the low-risk group, 3.5% in the intermediate-risk group and 17.2% in the high-risk group. In the validation cohort, 90-day mortality in the three groups was 0.6%, 3.9% and 19.6%, respectively. Compared with the low-risk group, the odds ratio for mortality was 43.5 for the high-risk group. The risk categories showed an area under the receiver operating characteristic curve of 0.79 in the derivation cohort and 0.82 in the validation cohort. <h3>Conclusions:</h3> The prognostic index accurately stratifies patients admitted to hospital for CAP into low-, intermediate- and high-risk groups for 90-day mortality on discharge. The use of this index could help clinicians improve outcomes in this vulnerable population by targeting specific interventions to each group.
Risk Factors for Suicide Completion in Major Depression: A Case-Control Study of Impulsive and Aggressive Behaviors in Men
Authors: A. Dumais, A.D. Lesage, M. Alda, G. Rouleau, M. Dumont, N. Chawky, M. Roy, J.J. Mann, C. Benkelfat, Gustavo Turecki
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Major depression is a major risk factor for suicide. However, not all individuals with major depression commit suicide. Impulsive and aggressive behaviors have been proposed as risk factors for suicide, but it remains unclear whether their effect on the risk of suicide is at least partly explained by axis I disorders commonly associated with suicide, such as major depression. With a case-control design, a comparison of the level of impulsive and aggressive behaviors and the prevalence of associated psychopathology was carried out with control for the presence of primary psychopathology. METHOD: One hundred and four male suicide completers who died during an episode of major depression and 74 living depressed male comparison subjects were investigated with proxy-based interviews by using structured diagnostic instruments and personality trait assessments. RESULTS: The authors found that current (6-month prevalence) alcohol abuse/dependence, current drug abuse/dependence, and cluster B personality disorders increased the risk of suicide in individuals with major depression. Also, higher levels of impulsivity and aggression were associated with suicide. An analysis by age showed that these risk factors were more specific to younger suicide victims (ages 18–40). A multivariate analysis indicated that current alcohol abuse/dependence and cluster B personality disorder were two independent predictors of suicide. CONCLUSIONS: Impulsive-aggressive personality disorders and alcohol abuse/dependence were two independent predictors of suicide in major depression, and impulsive and aggressive behaviors seem to underlie these risk factors. A developmental hypothesis of suicidal behavior, with impulsive and aggressive behaviors as the starting point, is discussed.
Cleavage of L1 in Exosomes and Apoptotic Membrane Vesicles Released from Ovarian Carcinoma Cells
Authors: Paul Gutwein, Alexander Stoeck, Svenja Riedle, Daniela Gast, Steffen Runz, Thomas P. Condon, Alexander Marmé, Minh-Chau Phong, Otwin Linderkamp, Alexander Skorokhod, Peter Altevogt
Journal: Clinical Cancer Research (2005)

The L1 adhesion molecule (CD171) is overexpressed in human ovarian and endometrial carcinomas and is associated with bad prognosis. Although expressed as a transmembrane molecule, L1 is released from carcinoma cells in a soluble form. Soluble L1 is present in serum and ascites of ovarian carcinoma patients. We investigated the mode of L1 cleavage and the function of soluble L1.We used ovarian carcinoma cell lines and ascites from ovarian carcinoma patients to analyze soluble L1 and L1 cleavage by Western blot analysis and ELISA.We find that in ovarian carcinoma cells the constitutive cleavage of L1 proceeds in secretory vesicles. We show that apoptotic stimuli like C2-ceramide, staurosporine, UV irradiation, and hypoxic conditions enhance L1-vesicle release resulting in elevated levels of soluble L1. Constitutive cleavage of L1 is mediated by a disintegrin and metalloproteinase 10, but under apoptotic conditions multiple metalloproteinases are involved. L1 cleavage occurs in two types of vesicles with distinct density features: constitutively released vesicles with similarity to exosomes and apoptotic vesicles. Both types of L1-containing vesicles are present in the ascites fluids of ovarian carcinoma patients. Soluble L1 from ascites is a potent inducer of cell migration and can trigger extracellular signal-regulated kinase phosphorylation.We suggest that tumor-derived vesicles may be an important source for soluble L1 that could regulate tumor cell function in an autocrine/paracrine fashion.
Novel &lt;EMPH TYPE="ITAL"&gt;hMLH1&lt;/EMPH&gt; and &lt;EMPH TYPE="ITAL"&gt;hMSH2&lt;/EMPH&gt; Germline Mutations in African Americans With Colorectal Cancer
Authors: Thomas K. Weber, Hyung Min Chin, Miguel Rodriguez-Bigas, Bernadette Keitz, Rebecca Gilligan, Linda O'Malley, Edwin Urf, Nazli Diba, James Pazik, Nicholas J. Petrelli
Journal: JAMA (1999)

Germline mutations of the DNA mismatch repair (MMR) genes hMLH1 and hMSH2 have been shown to cosegregate with the colorectal cancer phenotype in multiple hereditary nonpolyposis colorectal cancer (HNPCC) pedigrees. However, the frequency of these mutations among African American patients with colorectal cancer is unknown.
HFE gene variants and iron-induced oxygen radical generation in idiopathic pulmonary fibrosis
Authors: Federica Sangiuolo, Ermanno Puxeddu, Gabriella Pezzuto, Francesco Cavalli, Giuliana Longo, Alessia Comandini, Donato Di Pierro, Marco Pallante, Gianluigi Sergiacomi, Giovanni Simonetti, Maurizio Zompatori, Augusto Orlandi, Andrea Magrini, Massimo Amicosante, Francesca Mariani, Monica Losi, Daniela Fraboni, Alberto Bisetti, Cesare Saltini
Journal: European Respiratory Journal (2014)

In idiopathic pulmonary fibrosis (IPF), lung accumulation of excessive extracellular iron and macrophage haemosiderin may suggest disordered iron homeostasis leading to recurring microscopic injury and fibrosing damage. The current study population comprised 89 consistent IPF patients and 107 controls. 54 patients and 11 controls underwent bronchoalveolar lavage (BAL). Haemosiderin was assessed by Perls' stain, BAL fluid malondialdehyde (MDA) by high-performance liquid chromatography, BAL cell iron-dependent oxygen radical generation by fluorimetry and the frequency of hereditary haemochromatosis HFE gene variants by reverse dot blot hybridisation. Macrophage haemosiderin, BAL fluid MDA and BAL cell unstimulated iron-dependent oxygen radical generation were all significantly increased above controls (p<0.05). The frequency of C282Y, S65C and H63D HFE allelic variants was markedly higher in IPF compared with controls (40.4% versus 22.4%, OR 2.35, p=0.008) and was associated with higher iron-dependent oxygen radical generation (HFE variant 107.4±56.0, HFE wild type (wt) 59.4±36.4 and controls 16.7±11.8 fluorescence units per 10(5) BAL cells; p=0.028 HFE variant versus HFE wt, p=0.006 HFE wt versus controls). The data suggest iron dysregulation associated with HFE allelic variants may play an important role in increasing susceptibility to environmental exposures, leading to recurring injury and fibrosis in IPF.
Choline Kinase Activation Is a Critical Requirement for the Proliferation of Primary Human Mammary Epithelial Cells and Breast Tumor Progression
Authors: Ana Ramírez de Molina, Mónica Báñez-Coronel, Ruth Gutiérrez, Agustín Rodríguez-González, David Olmeda, Diego Megías, Juan Carlos Lacal
Journal: Cancer Research (2004)

Breast cancer is still one of the most important tumors among women in industrialized countries. Improvement in both understanding the molecular events associated with the disease and the development of new additional treatments is still an important goal to be achieved. Choline kinase (ChoK) is increased in human mammary tumors with high incidence, and this activation is associated with clinical variable indicators of greater malignancy. Here, we have investigated the role of ChoK in the development of breast cancer and found that ChoK is both necessary and sufficient for growth factor-induced proliferation in primary human mammary epithelial cells and an absolute requirement for the specific mitogenic response to heregulin in breast tumor-derived cells. These results demonstrate that ChoK plays an essential role in both normal human mammary epithelial cell proliferation and breast tumor progression. Furthermore, inhibition of ChoK shows a strong in vivo antitumor activity against human breast cancer xenografts. Thus, ChoK constitutes a novel bona fide molecular target for the treatment of breast cancer patients.
Otitis Media in Alaskan Eskimo Children
Authors: James E. Maynard
Journal: JAMA (1972)

In Alaska, acute suppurative otitis media has been reported as the second most frequent cause of morbidity in Aleut, Indian, and Eskimo children. A one-year double-blind prospective trial of ampicillin anhydrous taken orally as a prophylactic by 364 Eskimo children under the age of 7, residing in six villages in western Alaska, showed a 47% reduction in the incidence of otitis media. However, for children who took their medication well, the reduction in incidence was 67%.
Identification of Melanoma Antigens That Are Immunogenic in Humans and Expressed In Vivo
Authors: Jason Applebaum, Sandra Reynolds, Jeff Knispel, Ruth Oratz, Richard Shapiro, Jean-Claude Bystryn
Journal: JNCI Journal of the National Cancer Institute (1998)

Background. In the development of an antimelanoma vaccine, a critical factor is the identification of antigens that induce a strong immune response in humans and that are expressed by melanoma cells in vivo. The aim of this study was to identify candidate antigens for such vaccine. Methods: Sixtynine patients with surgically resected melanomas (American Joint Commission on Cancer [AJCC] stage III) were immunized with a polyvalent vaccine containing multiple melanoma antigens. Antimelanoma antibodies generated in the patients' sera were used as probes to identify the melanoma antigens that are immunogenic in humans and that are expressed on the tumor tissue in vivo. Such responses were determined by an immunoblotting assay that employed an antigen source prepared from membrane fractions of freshly excised melanoma tissue. Results and Conclusions: Vaccine treatment stimulated antibody responses in 35 (51%; 95% confidence interval [CI] = 39%–63%) of 69 sequentially enrolled patients. The antibodies were directed to one or more antigens with molecular masses of 45, 59, 68, 79, 89, 95, and/or 110 kd. The most immunogenic antigens were p110 and p68, which induced responses in 33% (95% CI = 22%∓44%) and 25% (95% CI = 15%-35%) of patients, respectively. Both antigens were commonly expressed on different melanomas, but they were absent on autologous normal tissue and on an unrelated allogeneic tumor. All the above antigens are attractive candidates for vaccine construction. [J Nall Cancer Inst 1998;90: 146-9]