tbuckley/cabot-search huggingface dataset:
Psychological status in COPD patients of Kirov region
Authors: Vasily Pyankov, Yulia Chuyasova
Journal: European Respiratory Journal (2013)

Purpose: To estimate the quality of life (QOL) and prevalence of anxiety and depression in COPD patients of Kirov region.

Materials and Methods: 160 COPD patients of Kirov region were included in the study (mean age 65.1±10.4 years, 132 males and 28 females). All patients were examined using Hospital Anxiety and Depression Scale (HADS). The following additional methods were used: Hamilton Rating Scale for Depression (HRSD) and AQ 20 QOL Questionnaire (AQ 20).

Results: The prevalence of anxiety in COPD patients was 57.5% of cases (92 patients): subclinical HADS-anxiety - in 41.2% (66 patients), clinical HADS-anxiety – in 16.3% (26 patients). The prevalence of depression was 35% in the above cases (56 patients): subclinical HADS-depression - in 26.2% (42 patients), clinical HADS-depression - in 8.8% (14 patients). There were significant correlations between HADS-anxiety score and age (r=0.43; p=0.001), HADS-depression score and age (r=0.54; p=0.001), HADS-anxiety score and level of COPD severity (r=0.42; p=0.001), HADS-depression score and level of COPD severity (r=0.45; p=0.001). Also we detected significant correlations between HADS-anxiety score and HRSD score (r=0.87; p=0.001), HADS-depression score and HRSD score (r=0.77; p=0.001), HADS-anxiety score and AQ 20 score (r=0.61; p=0.001), HADS-depression score and AQ 20 score (r=0.46; p=0.001).

Conclusions: Our study confirmed high prevalence of anxiety and depression in COPD patients of Kirov region. Anxiety and depression are serious but potentially remediable disorders. Physicians should detect these problems in patients with COPD. HADS is a simple and rapid tool to detect anxiety and depression in COPD patients.
A feasibility study of sequential doublet chemotherapy comprising carboplatin–doxorubicin and carboplatin–paclitaxel for advanced endometrial adenocarcinoma and carcinosarcoma
Authors: J.E. Ang, R.N. Shah, M. Everard, C. Keyzor, I. Coombes, A. Jenkins, K. Thomas, R. A'Hern, R.L. Jones, P. Blake, H. Gabra, G. Hall, M.E. Gore, S.B. Kaye
Journal: Annals of Oncology (2009)
The Human Papillomavirus E6 Oncogene Dysregulates the Cell Cycle and Contributes to Cervical Carcinogenesis through Two Independent Activities
Authors: Anny Shai, Tiffany Brake, Chamorro Somoza, Paul F. Lambert
Journal: Cancer Research (2007)

Cervical cancer is a leading cause of death due to cancer among women worldwide. Using transgenic mice to dissect the contributions of the human papillomavirus (HPV) 16 E6 and E7 oncogenes in cervical cancer, E7 was identified previously to be the dominant oncogene. Specifically, when treated with exogenous estrogen for 6 months, E7 transgenic mice developed cancer throughout the reproductive tract, but E6 transgenic mice did not. E6 contributed to carcinogenesis of the reproductive tract, as E6/E7 double transgenic mice treated for 6 months with estrogen developed larger cancers than E7 transgenic mice. In the current study, we investigated whether the E6 oncogene alone could cooperate with estrogen to induce cervical cancer after an extended estrogen treatment period of 9 months. We found that the E6 oncogene synergizes with estrogen to induce cervical cancer after 9 months, indicating that E6 has a weaker but detectable oncogenic potential in the reproductive tract compared with the E7 oncogene. Using transgenic mice that express mutant forms of HPV16 E6, we determined that the interactions of E6 with cellular alpha-helix and PDZ partners correlate with its ability to induce cervical carcinogenesis. In analyzing the tumors arising in E6 transgenic mice, we learned that E6 induces expression of the E2F-responsive genes, Mcm7 and cyclin E, in the absence of the E7 oncogene. E6 also prevented the expression of p16 in tumors of the reproductive tract through a mechanism mediated by the interaction of E6 with alpha-helix partners.
Notch1 loss of heterozygosity causes vascular tumors and lethal hemorrhage in mice
Authors: Zhenyi Liu, Ahu Turkoz, Erin N. Jackson, Joseph C. Corbo, John A. Engelbach, Joel R. Garbow, David R. Piwnica-Worms, Raphael Kopan
Journal: Journal of Clinical Investigation (2011)

The role of the Notch signaling pathway in tumor development is complex, with Notch1 functioning either as an oncogene or as a tumor suppressor in a context-dependent manner. To further define the role of Notch1 in tumor development, we systematically surveyed for tumor suppressor activity of Notch1 in vivo. We combined the previously described Notch1 intramembrane proteolysis–Cre (Nip1::Cre) allele with a floxed Notch1 allele to create a mouse model for sporadic, low-frequency loss of Notch1 heterozygosity. Through this approach, we determined the cell types most affected by Notch1 loss. We report that the loss of Notch1 caused widespread vascular tumors and organism lethality secondary to massive hemorrhage. These findings reflected a cell-autonomous role for Notch1 in suppressing neoplasia in the vascular system and provide a model by which to explore the mechanism of neoplastic transformation of endothelial cells. Importantly, these results raise concerns regarding the safety of chronic application of drugs targeting the Notch pathway, specifically those targeting Notch1, because of mechanism-based toxicity in the endothelium. Our strategy also can be broadly applied to induce sporadic in vivo loss of heterozygosity of any conditional alleles in progenitors that experience Notch1 activation.
SERUM TRANSAMINASE TESTS FOR LIVER FUNCTION ON OUTPATIENTS IN FOLLOW-UP CLINIC
Authors: YUDELL K. SLOCUM
Journal: American Journal of Psychiatry (1961)

The dosage of ataraxics which these patients were receiving was considered to be their maintenance dosage and the smallest amount of treatment necessary, which may be the reason for the negative reports of liver damage. The effect of the medication on the individual patient, not the medicine or chemicals themselves, must be the primary consideration in all treatments(4). It is felt that the medication has kept these patients out of hospitals and helped them in adjusting for prolonged periods without the risk of harmful effects on the liver, even though they are not cured of their original mental illnesses(5).
Genetic Risk and Breast Cancer Survival: Another Link in the Chain of Evidence
Authors: W. Burke, M. B. Laya
Journal: JNCI Journal of the National Cancer Institute (1999)

The discovery of the BRCA1 and BRCA2 genes was an important milestone in breast cancer research. Ongoing investigation of cancer genes is sure to improve our knowledge of cancer biology and may speed development of new cancer treatments and prevention strategies. As this research effort goes forward, however, puzzling questions need to be addressed concerning the clinical effects of mutations in the BRCA1 and BRCA2 genes. We do not understand why the degree of cancer risk conferred by mutations is variable or why some mutation carriers develop breast cancer, others develop ovarian cancer, and some develop both. We do not know whether the cancers occurring in mutation carriers are essentially the same or significantly different from those occurring in noncarriers. Breast cancer occurs at an earlier age in mutation carriers, and a higher prevalence of adverse pathobiologic features has been reported in breast cancers occurring in BRCA1 mutation carriers. (1). These observations raise concern that mutationassociated cancers are more aggressive and result in higher mortality rates. A new study (2) reported in this issue of the Journal addresses the question of cancer survival. Lee et al. found no difference in breast or ovarian cancer survival by mutation status. This conclusion was based on a survey of Ashkenazi Jewish
Mevastatin Can Cause G <sub>1</sub> Arrest and Induce Apoptosis in Pulmonary Artery Smooth Muscle Cells Through a p27 <sup>Kip1</sup> -Independent Pathway
Authors: Brian W. Fouty, David M. Rodman
Journal: Circulation Research (2003)

Advanced pulmonary arterial hypertension is characterized by extensive vascular remodeling that is usually resistant to vasodilator therapy. Mevastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting step for cholesterol synthesis. HMG-CoA reductase inhibitors have been shown to upregulate the cyclin-dependent kinase inhibitor p27Kip1 and to block cell proliferation through cholesterol-independent pathways. The aim of this study was to determine the effect of mevastatin on DNA synthesis, cell cycle progression, and cell proliferation in rat pulmonary artery smooth muscle cells (PASMCs). We found that mevastatin induced G1 arrest and decreased DNA synthesis in rat PASMCs and did so in association with an increase in both total and cyclin E-bound p27Kip1. This caused a marked decrease in cyclin E kinase activity, which suggests an important role for p27Kip1 in the ability of mevastatin to induce G1 arrest. However, in PASMCs lacking functional p27Kip1, mevastatin still decreased cyclin E kinase activity, caused G1 arrest, and decreased DNA synthesis. In p27Kip1-deficient PASMCs, mevastatin induced a greater reduction of cyclin E protein levels (to 35% of control) than in wild-type cells (to 70% of control) and also reduced the phosphorylation of cdk2 on threonine 160. Mevastatin also caused apoptosis in both wild-type and p27Kip1-deficient PASMCs and was able to do so at a dose that did not induce cell cycle arrest. These data suggest that HMG-CoA reductase inhibitors can both inhibit cell proliferation and induce apoptosis in PASMCs through p27Kip1-independent pathways and may be important therapeutic agents in pulmonary arterial hypertension.
The Outcome of Patients Treated with Sunitinib Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer
Authors: Thomas Powles, Christian Blank, Simon Chowdhury, Simon Horenblas, John Peters, Jonathan Shamash, Naveed Sarwar, Ekaterini Boleti, Anju Sahdev, Tim O'Brien, Dan Berney, Luis Beltran, Paul Nathan, John Haanen, Axel Bex
Journal: European Urology (2011)
Preclinical Assessment of the Effectiveness of α-Dectin-1-Pam3 Conjugate in Controlling TH2 Responses
Authors: Katherine C. Upchurch, Joshua Horton, HyeMee Joo, Wei Zhang, Jerome Ellis, Sandy Zurawski, Robert L. Coffman, Gerard Zurawski, Bob Kane, Lisa Miller, Sangkon Oh
Journal: Journal of Allergy and Clinical Immunology (2015)
Etiology of Solitary Extrapulmonary Positron Emission Tomography and Computed Tomography Findings in Patients With Lung Cancer
Authors: Didier Lardinois, Walter Weder, Marina Roudas, Gustav K. von Schulthess, Michaela Tutic, Holger Moch, Rolf A. Stahel, Hans C. Steinert
Journal: Journal of Clinical Oncology (2005)

The aim of this prospective study was to assess the incidence and the nature of solitary extrapulmonary [18F] fluorodeoxyglucose (FDG) accumulations in patients with non-small-cell lung cancer (NSCLC) staged with integrated positron emission tomography and computed tomography (PET/CT) and to evaluate the impact on management.A total of 350 patients with NSCLC underwent whole-body PET/CT imaging. All solitary extrapulmonary FDG accumulations were evaluated by histopathology, further imaging, or clinical follow-up.PET/CT imaging revealed extrapulmonary lesions in 110 patients. In 72 patients (21%), solitary lesions were present. A diagnosis was obtained in 69 of these patients, including 37 (54%) with solitary metastases and 32 (46%) with lesions unrelated to the lung primary. Histopathologic examinations of these 32 lesions revealed a second clinically unsuspected malignancy or a recurrence of a previous diagnosed carcinoma in six patients (19%) and a benign tumor or inflammatory lesion in 26 patients (81%). The six malignancies consisted of carcinoma of the breast in two patients, and carcinoma of the orbit, esophagus, prostate, and non-Hodgkin's lymphoma in one patient each. Benign tumors and inflammatory lesions included eight colon adenomas, four Warthin's tumors, one granuloma of the lower jaw, one adenoma of the thyroid gland, one compensatory muscle activity due to vocal chord palsy, two occurrences of arthritis, three occurrences of reflux esophagitis, two occurrences of pancreatitis, two occurrences of diverticulitis, one hemorrhoidal inflammation, and one rib fracture.Solitary extrapulmonary FDG accumulations in patients with newly diagnosed lung cancer should be analyzed critically for correct staging and optimal therapy, given that up to half of the lesions may represent unrelated malignancies or benign disease.
Abnormal apical cell membrane in cystic fibrosis respiratory epithelium. An in vitro electrophysiologic analysis.
Authors: C U Cotton, M J Stutts, M R Knowles, J T Gatzy, R C Boucher
Journal: Journal of Clinical Investigation (1987)

The transepithelial chloride permeability of airway and sweat ductal epithelium has been reported to be decreased in patients with cystic fibrosis (CF). In the present study, we investigated whether the airway epithelial defect was in the cell path by characterizing the relative ion permeabilities of the apical membrane of respiratory epithelial cells from CF and normal subjects. Membrane electric potential difference (PD) and the responses to luminal Cl- replacement, isoproterenol, and amiloride were measured with intracellular microelectrodes. The PD across the apical barrier was smaller for CF (-11 mV) than normal (-29 mV) epithelia whereas the PD across the basolateral barrier was similar, (-26 and -34 mV respectively). In contrast to normal nasal epithelium, the apical membrane in CF epithelia was not Cl- permselective and was not responsive to isoproterenol. Amiloride, a selective Na+ channel blocker, induced a larger apical membrane hyperpolarization and a greater increase in transepithelial resistance in CF epithelia. Both reduced apical cell membrane Cl- conductance and increased Na+ conductance appear to contribute to the abnormal function of respiratory epithelia of CF patients.
Computed tomography for determining liver iron content in primary haemochromatosis.
Authors: R W Chapman, G Williams, G Bydder, R Dick, S Sherlock, L Kreel
Journal: BMJ (1980)

Dual-energy computed tomography (CT) was used to estimate hepatic iron concentration in eight patients with primary haemochromatosis with varying degrees of iron overload. The values corresponded closely with these derived from chemical analysis of liver tissue obtained by biopsy (correlation coefficient 0.993). Dual-energy CT therefore seems to provide an accurate and non-invasive alternative to liver biopsy as a means of measuring liver iron concentration in patients with primary haemochromatosis and possibly other iron overload states.
MK2 controls the level of negative feedback in the NF-κB pathway and is essential for vascular permeability and airway inflammation
Authors: Magdalena M. Gorska, Qiaoling Liang, Susan J. Stafford, Nicolas Goplen, Nilesh Dharajiya, Lei Guo, Sanjiv Sur, Matthias Gaestel, Rafeul Alam
Journal: The Journal of Experimental Medicine (2007)

We demonstrate that mitogen-activated protein kinase–activated kinase-2 (MK2) is essential for localized Th2-type inflammation and development of experimental asthma. MK2 deficiency does not affect systemic Th2 immunity, but reduces endothelial permeability, as well as adhesion molecule and chemokine expression. NF-κB regulates transcription of adhesion molecules and chemokines. We show that MK2 and its substrate HSP27 are essential for sustained NF-κB activation. MK2 and HSP27 prevent nuclear retention of p38 by sequestering it in the cytosol. As a result, MK2 precludes excessive phosphorylation of MSK1. By reducing MSK1 activity, MK2 prevents p65 NF-κB hyperphosphorylation and excessive IκBα transcription. IκBα mediates nuclear export of p65. By reducing IκBα level, MK2 prevents premature export of NF-κB from the nucleus. Thus, the MK2–HSP27 pathway regulates the NF-κB transcriptional output by switching the activation pattern from high level, but short lasting, to moderate-level, but long lasting. This pattern of activation is essential for many NF-κB–regulated genes and development of inflammation. Thus, the MK2–HSP27 pathway is an excellent target for therapeutic control of localized inflammatory diseases.
Left ventricular dysfunction in Duchenne Muscular Distrophy: Early detection by Tissue Doppler Imaging
Authors: A. Lombardo, L. De Luca, A. Dello Russo, C. Santini, V. Giglio, L. Messano, E. Ricci, F. Bellocci, F. Pennestrì, F. Loperfido
Journal: European Journal of Heart Failure (2000)
Functional Assays for Classification of<i>BRCA2</i>Variants of Uncertain Significance
Authors: Daniel J. Farrugia, Mukesh K. Agarwal, Vernon S. Pankratz, Amie M. Deffenbaugh, Dmitry Pruss, Cynthia Frye, Linda Wadum, Kiley Johnson, Jennifer Mentlick, Sean V. Tavtigian, David E. Goldgar, Fergus J. Couch
Journal: Cancer Research (2008)

Abstract The assessment of the influence of many rare BRCA2 missense mutations on cancer risk has proved difficult. A multifactorial likelihood model that predicts the odds of cancer causality for missense variants is effective, but is limited by the availability of family data. As an alternative, we developed functional assays that measure the influence of missense mutations on the ability of BRCA2 to repair DNA damage by homologous recombination and to control centriole amplification. We evaluated 22 missense mutations from the BRCA2 DNA binding domain (DBD) that were identified in multiple breast cancer families using these assays and compared the results with those from the likelihood model. Thirteen variants inactivated BRCA2 function in at least one assay; two others truncated BRCA2 by aberrant splicing; and seven had no effect on BRCA2 function. Of 10 variants with odds in favor of causality in the likelihood model of 50:1 or more and a posterior probability of pathogenicity of 0.99, eight inactivated BRCA2 function and the other two caused splicing defects. Four variants and four controls displaying odds in favor of neutrality of 50:1 and posterior probabilities of pathogenicity of at least 1 × 10−3 had no effect on function in either assay. The strong correlation between the functional assays and likelihood model data suggests that these functional assays are an excellent method for identifying inactivating missense mutations in the BRCA2 DBD and that the assays may be a useful addition to models that predict the likelihood of cancer in carriers of missense mutations. [Cancer Res 2008;68(9):3523–31]
Competition and the Mental Health System
Authors: Alison Evans Cuellar, Deborah Haas-Wilson
Journal: American Journal of Psychiatry (2009)

In the 1970s, mental health services were largely both publicly funded and publicly provided, but today service provision has shifted toward the private sector (1).As a result, the mental health care system increasingly relies on competition to allocate health care resources.In 2003, mental health services constituted 6.2% of all U.S. health spending or $100 billion (2).Competition for consumers-whether among insurers, hospitals, physicians, or others-largely determines which mental health services are produced, how they are produced, and at what prices they are produced.Below we discuss three notable features of the competitive mental health care market and their policy implications.
Carcinogenicity of Epoxides, Lactones, and Peroxy Compounds. IV. Tumor Response in Epithelial and Connective Tissue in Mice and Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B. L. van Duuren, L. Langseth, L. Orris, G. Teebor, N. Nelson, M. Kuschner
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Carcinogenicity of Epoxides, Lactones, and Peroxy Compounds. IV. Tumor Response in Epithelial and Connective Tissue in Mice and Rats Get access B. L. van Duuren, B. L. van Duuren Institute of Environmental Medicine and Department of Pathology, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Langseth, L. Langseth Institute of Environmental Medicine and Department of Pathology, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Orris, L. Orris Institute of Environmental Medicine and Department of Pathology, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Teebor, G. Teebor Institute of Environmental Medicine and Department of Pathology, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Nelson, N. Nelson Institute of Environmental Medicine and Department of Pathology, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar M. Kuschner M. Kuschner Institute of Environmental Medicine and Department of Pathology, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 37, Issue 6, December 1966, Pages 825–838, https://doi.org/10.1093/jnci/37.6.825 Published: 01 December 1966 Article history Received: 06 June 1966 Published: 01 December 1966
THE ASSOCIATION OF SKIN-SENSITIZING ANTIBODY WITH THE ß2A-GLOBULINS IN SERA FROM RAGWEED-SENSITIVE PATIENTS
Authors: Philip Fireman, Wilton E. Vannier, Howard C. Goodman
Journal: The Journal of Experimental Medicine (1963)

1. The removal of the beta(2)A-globulins from three sera from treated ragweed-sensitive individuals by immune absorption was associated with the loss of all detectable skin-sensitizing antibody activity as demonstrated by Prausnitz-Küstner testing. 2. Gel filtration studies, with sephadex G-200, indicated that the fractions containing only macroglobulins were devoid of all detectable skin-sensitizing antibody activity. 3. The immune absorption of the gamma-globulins from a serum fraction containing beta(2)A-globulins, gamma-globulins, and a trace of beta(2)M-globulins had no detectable influence on the skin-sensitizing antibody activity. 4. The removal of a portion of the albumin from the allergic sera by immune absorption, with retention of the skin-sensitizing activity, indicated that the loss of skin-sensitizing antibody was not due to non-specific absorption on an antigen-antibody precipitate. 5. No inhibition of the Prausnitz-Küstner reaction was observed when sheep serum, normal human serum, or normal human gamma-globulins were tested in concentrations described. 6. We conclude that the skin-sensitizing antibody activities in the three sera from treated ragweed-sensitive individuals studied were associated with the beta(2)A-globulins.