tbuckley/cabot-search huggingface dataset:
Impact of obstructive airways disease on quality of life in older adults.
Authors: D. S. Renwick, M. J. Connolly
Journal: Thorax (1996)

Obstructive airways disease adversely affects quality of life, although relationships between quality of life and lung function have been shown to be weak. The relationships between the results of a quality of life questionnaire, spirometric tests, and methacholine bronchial challenge were investigated in a population sample of middle aged and elderly people.A random population sample of the white population of Central Manchester, UK were contacted by post. Respondents were invited to undergo bronchial challenge with methacholine (Newcastle dosimeter method) and to complete the St George's Respiratory Questionnaire. This self-completed questionnaire quantifies quality of life as three component scores, with higher scores indicating greater impairment of quality of life.Two hundred and twenty seven subjects aged 45-86 years completed the St George's Questionnaire and performed spirometric tests; 190 completed the methacholine challenge. All quality of life scores were higher in subjects with a forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of < 65%, indicating impaired quality of life in subjects with airways obstruction. There was no relationship between quality of life and age. Multiple regression analysis showed independent relationships between quality of life scores and both baseline FEV1 and bronchial responsiveness. However, the amount of variation in quality of life attributable to variation in FEV1 or bronchial responsiveness was less than 10%. Subgroup analysis indicated that the quality of life score was independently associated with bronchial responsiveness and not FEV1 in subjects aged < 65 years, but with baseline FEV1 and not bronchial responsiveness in older subjects.Obstructive airways disease significantly impairs quality of life in adults. The reduction in quality of life in these patients is related to both baseline pulmonary function and non-specific bronchial responsiveness. The impact of airways obstruction on quality of life does not decrease with advancing age.
Low Evolutionary Diversification in a Widespread and Abundant Uncultured Protist (MAST-4)
Authors: R. Rodriguez-Martinez, G. Rocap, R. Logares, S. Romac, R. Massana
Journal: Molecular Biology and Evolution (2011)

Recent culture-independent studies of marine planktonic protists have unveiled a large diversity at all phylogenetic scales and the existence of novel groups. MAST-4 represents one of these novel uncultured lineages, and it is composed of small (∼2 μm) bacterivorous eukaryotes that are widely distributed in marine systems. MAST-4 accounts for a significant fraction of the marine heterotrophic flagellates at the global level, playing key roles in the marine ecological network. In this study, we investigated the diversity of MAST-4, aiming to assess its limits and structure. Using ribosomal DNA (rDNA) sequences obtained in this study (both pyrosequencing reads and clones with large rDNA operon coverage), complemented with GenBank sequences, we show that MAST-4 is composed of only five main clades, which are well supported by small subunit and large subunit phylogenies. The differences in the conserved regions of the internal transcribed spacers 1 and 2 (ITS1 and ITS2) secondary structures strongly suggest that these five clades are different biological species. Based on intraclade divergence, ITS secondary structures and comparisons of ITS1 and ITS2 trees, we did not find evidence of more than one species within clade A, whereas as many as three species might be present within other clades. Overall, the genetic divergence of MAST-4 was surprisingly low for an organism with a global population size estimated to be around 1024, indicating a very low evolutionary diversification within the group.
Medium- and Large-Vessel Vasculitis
Authors: Cornelia M. Weyand, Jörg J. Goronzy
Journal: New England Journal of Medicine (2003)

Giant-cell arteritis typically involves extracranial branches of the aorta, such as the temporal and vertebral arteries. Temporal arteritis and polymyalgia rheumatica often coexist, and systemic manifestations of inflammation occur in virtually all forms of giant-cell arteritis. This article reviews the mechanisms that contribute to the causes of giant-cell arteritis, with an emphasis on immune-mediated injury to arteries.
Triple-Negative Breast Cancer: Risk Factors to Potential Targets
Authors: Bryan P. Schneider, Eric P. Winer, William D. Foulkes, Judy Garber, Charles M. Perou, Andrea Richardson, George W. Sledge, Lisa A. Carey
Journal: Clinical Cancer Research (2008)

Triple-negative breast cancer has recently been recognized as an important subgroup of breast cancer with a distinct outcome and therapeutic approach when compared with other subgroups of breast cancer. Triple-negative breast cancer comprises primarily, but not exclusively, a molecularly distinct subtype of breast cancer, the basal-like subtype. We do not yet have an assay to identify basal-like breast cancer in clinical samples, so triple-negative breast cancer has become a commonly used proxy for this subtype. The molecular biology and pathophysiology of triple-negative breast cancer are not completely understood, but understanding is improving rapidly with the advent of sophisticated molecular biology platforms. Moreover, the established risk factors of breast cancer as a whole may not apply to this unique subgroup of patients. Finally, because triple-negative breast cancer is defined by the absence of a target, there are currently limitations to using a tailored therapeutic approach, leaving conventional cytotoxic therapies as the mainstay. Active preclinical and clinical research programs focus on defining the clinical behavior, delineating the risk factors, and more completely understanding the molecular biology of triple-negative breast cancer to improve prevention, optimize conventional agents, and unveil novel therapeutic targets. This CCR focus article will review the current state of the art on triple-negative breast cancer.
Practolol in Treatment of Supraventricular Cardiac Dysrhythmias
Authors: G. Gent, T. C. Davis, A. McDonald
Journal: BMJ (1970)

Practolol (I.C.I. 50172) was used to treat supraventricular dysrhythmias in 32 patients with a rapid ventricular rate and with heart disease of varied aetiology. In 26 patients the average reduction in ventricular rate was 75 per minute, while immediate reversion to sinus rhythm occurred in three patients. The slowing effect was mainly due to a direct action on the atrioventricular node. The effectiveness of practolol was unrelated to the type of dysrhythmia or its aetiology. No serious adverse clinical effects were noted.
Acetylcholinesterase in the Conductive Tissue of the Heart
Authors: W. F. H. M. MOMMAKRTS, P. A. KHAIRALLAH, MARY FLEMING DICKENS
Journal: Circulation Research (1953)

It is shown that the Purkinje system of bovine hearts contains a specific acetylcholinesterase resembling that of nervous tissue, in an amount comparable to that of peripheral nerve. Its possible implication in the conduction of impulses in the heart is discussed.
Arsenic inhibition of telomerase transcription leads to genetic instability
Authors: Wen-Chien Chou, Anita L. Hawkins, John F. Barrett, Constance A. Griffin, Chi V. Dang
Journal: Journal of Clinical Investigation (2001)

Arsenic is effective in the treatment of acute promyelocytic leukemia. Paradoxically, it is also carcinogenic. In the process of elucidating a mechanism of arsenic resistance in a leukemia cell line, NB4, we discovered that arsenic exposure causes chromosomal abnormalities, with a preponderance of end-to-end fusions. These chromosomal end fusions suggested that telomerase activity may be inhibited by arsenic. We found that arsenic inhibits transcription of the hTERT gene, which encodes the reverse transcriptase subunit of human telomerase. This effect may in part be explained by decreased c-Myc and Sp1 transcription factor activities. Decreased telomerase activity leads to chromosomal end lesions, which promote either genomic instability and carcinogenesis or cancer cell death. These phenomena may explain the seemingly paradoxical carcinogenic and antitumor effects of arsenic.
Echo enhanced ultrasound: a new valid initial imaging approach for severe acute pancreatitis
Authors: S Rickes
Journal: Gut (2005)

<b>Aim:</b> This prospective study aimed to compare the accuracy of echo enhanced ultrasound with spiral computed tomography (CT) in assessing acute pancreatitis and to explore the correlation between ultrasound findings and clinical outcome. <b>Methods:</b> Thirty one patients (24 men and 7 women, median age 39 years, range 19–67 years) with acute pancreatitis were investigated by contrast enhanced CT and echo enhanced ultrasound within 72 hours after admission. Echo enhanced ultrasound (with intravenous injection of 2.4 ml SonoVue, pulse inversion technique, mechanical index 0.1 to 0.2, Siemens Elegra) was performed following conventional ultrasound. Balthazar's grading system was used to measure CT and ultrasound severity indices (CTSI and USSI). Correlations between CTSI and USSI and between USSI and clinical parameters were tested by Spearman's rank correlation coefficient. <b>Results:</b> A strong correlation was demonstrated between CTSI and USSI (<i>r</i> = 0.807, p&lt;0.01). Ultrasound correlated with the following: the Ranson score (<i>r</i> = 0.401, p&lt;0.05), C-reactive protein levels 48 hours after admission (<i>r</i> = 0.536, p&lt;0.01), duration of hospitalisation (<i>r</i> = 0.422, p&lt;0.05), and clinical outcome regarding morbidity, including local and systemic complications (<i>r</i> = 0.363, p&lt;0.05). Based on CT findings as the gold standard, sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound for detecting severe acute pancreatitis based on imaging criteria (Balthazar score D or E and/or presence of hypoperfusion compatible with necrosis and/or SI⩾3) were, respectively, 82% (95% CI 61 to 93), 89% (95% CI 57 to 98), 95% (95% CI 75 to 99), and 67% (95% CI 39 to 86). <b>Conclusion:</b> Echo enhanced ultrasound produces excellent results in the staging of acute pancreatitis severity. The procedure is cheaper and has fewer contraindications than CT. Further multicentre studies need to be performed before including the method in the diagnostic algorithm of patients with acute pancreatitis.
Impact of Infectious Burden on Extent and Long-Term Prognosis of Atherosclerosis
Authors: Christine Espinola-Klein, Hans J. Rupprecht, Stefan Blankenberg, Christoph Bickel, Helmuth Kopp, Gerd Rippin, Anja Victor, Gerd Hafner, Wolfgang Schlumberger, Jürgen Meyer
Journal: Circulation (2002)

Recent findings suggest a causative role of infections in the pathogenesis of atherosclerosis. In hypothesizing an association between infectious agents and the development of atherosclerosis, we would expect a correlation to the extent of atherosclerosis. Moreover, this effect could be multiplied by the number of pathogens to which an individual had been exposed.In 572 patients, IgG or IgA antibodies to herpes simplex virus 1 and 2, cytomegalovirus, Epstein-Barr virus, Hemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were measured. The extent of atherosclerosis was determined by coronary angiography, carotid duplex sonography, and evaluation of the ankle-arm index. Elevated IgA antibodies against C pneumoniae (P<0.04) and IgG antibodies against H pylori (P<0.02), cytomegalovirus (P<0.05), and herpes simplex virus 2 (P<0.01) were associated with advanced atherosclerosis (> or =2 vascular regions), adjusted for age, sex, cardiovascular risk factors, and highly sensitive C-reactive protein. Infectious burden divided into 0 to 3, 4 to 5, and 6 to 8 seropositivities was significantly associated with advanced atherosclerosis, with an odds ratio (95% CI) of 1.8 (1.2 to 2.6) for 4 to 5 (P<0.01) and 2.5 (1.2 to 5.1) for 6 to 8 seropositivities (P<0.02) (adjusted). After a mean follow-up of 3.2 years, cardiovascular mortality rate was 7.0% in patients with advanced atherosclerosis and seropositive for 0 to 3 pathogens compared with 20.0% in those seropositive for 6 to 8 pathogens.Our results support the hypothesis that infectious agents are involved in the development of atherosclerosis. We showed a significant association between infectious burden and the extent of atherosclerosis. Moreover, the risk for future death was increased by the number of infectious pathogens, especially in patients with advanced atherosclerosis.
861-2 Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin, and an early conservation initial management strategy: Results from the A phase of the A to Z trial
Authors: James A de Lemos, Michael A Blazing, Harvey D White, Keith A Fox, Peter M DiBattiste, Joanne Palmisano, David W Bilheimer, William E Brady, Laura H Gardner, Karen E Ramsey, Eldrin F Lewis, Marc A Pfeffer, Robert M Califf, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2004)
Pancreatic Cancer Metastases Harbor Evidence of Polyclonality
Authors: Ravikanth Maddipati, Ben Z. Stanger
Journal: Cancer Discovery (2015)

Studies of the cancer genome have demonstrated that tumors are composed of multiple subclones with varied genetic and phenotypic properties. However, little is known about how metastases arise and evolve from these subclones. To understand the cellular dynamics that drive metastasis, we used multicolor lineage-tracing technology in an autochthonous mouse model of pancreatic cancer. Here, we report that precursor lesions exhibit significant clonal heterogeneity but that this diversity decreases during premalignant progression. Furthermore, we present evidence that a significant fraction of metastases are polyclonally seeded by distinct tumor subclones. Finally, we show that clonality during metastatic growth-leading to either monoclonal or polyclonal expansion-differs based on the site of metastatic invasion. These results provide an unprecedented window into the cellular dynamics of tumor evolution and suggest that heterotypic interactions between tumor subpopulations contribute to metastatic progression in native tumors.
Embryonic Stem Cell-Like Features of Testicular Carcinoma <b> <i>in Situ</i> </b> Revealed by Genome-Wide Gene Expression Profiling
Authors: Kristian Almstrup, Christina E. Hoei-Hansen, Ute Wirkner, Jonathon Blake, Christian Schwager, Wilhelm Ansorge, John E. Nielsen, Niels E. Skakkebæk, Ewa Rajpert-De Meyts, Henrik Leffers
Journal: Cancer Research (2004)

Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly expressed in testicular CIS, including many never reported in testicular neoplasms. Expression was further verified by semiquantitative reverse transcription-PCR and in situ hybridization. Among the highest expressed genes were NANOG and POU5F1, and reverse transcription-PCR revealed possible changes in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported as unstable in cultured ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS. Moreover, the findings are consistent with an early prenatal origin of TGCTs and thus suggest that etiologic factors operating in utero are of primary importance for the incidence trends of TGCTs. Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs.
Effect of Recombinant Adenovirus-p53 Combined With Radiotherapy on Long-Term Prognosis of Advanced Nasopharyngeal Carcinoma
Authors: Jian-ji Pan, Shan-wen Zhang, Chuan-beng Chen, Shao-wen Xiao, Yan Sun, Chang-qin Liu, Xing Su, Dong-ming Li, Gang Xu, Bo Xu, You-yong Lu
Journal: Journal of Clinical Oncology (2008)

Purpose To centrally assess the safety, efficacy, and 6-year follow-up of recombinant adenovirus-p53 (rAd-p53) combined with radiotherapy (RT) for patients with nasopharyngeal carcinoma (NPC). Patients and Methods A randomized controlled clinical study on rAd-p53 combined with RT in 42 patients with NPC was compared with a control group of 40 patients with NPC treated with RT alone. In the group receiving rAd-p53 combined with RT, rAd-p53 was intratumorally injected once a week for 8 weeks. Concurrent RT (70 Gy in 35 fractions) was given to the nasopharyngeal tumor and neck lymph node. Patients and tumors were monitored for adverse events and responses. Results rAd-p53–specific p53 mRNA was detected in postinjection of rAd-p53 biopsies from 16 (94.1%) of 17 patients. Upregulation of p21/WAF1 and Bax and downregulation of vascular endothelial growth factor were observed in postinjection tumor biopsy. Complete response rate in the group receiving rAd-p53 combined with RT was observed at 2.73 times that of the group receiving RT alone (66.7% v 24.4%). Six-year follow-up data showed that rAd-p53 significantly increased the 5-year locoregional tumor control rate by 25.3% for patients with NPC treated with irradiation (P = .002). The 5-year overall survival rate and 5-year disease-free survival rate of the group receiving rAd-p53 combined with RT were 7.5% (P = .34) and 11.7% (P = .21) higher than those of the group receiving RT alone. No dose-limiting toxicity or adverse events appeared, except for transient fever after rAd-p53 administration. Conclusion In patients with NPC, rAd-p53 was safe and biologically active. Our results indicated that rAd-p53 improves radiotherapeutic tumor control and survival rate in patients with NPC.
CYTOLOGIC STUDIES ON RHEUMATIC FEVER
Authors: Currier McEwen
Journal: The Journal of Experimental Medicine (1932)

Scrapings of subcutaneous nodules from ten patients with rheumatic fever were examined microscopically after being stained with supravital dyes. From the uniform results obtained, the following conclusions have been drawn. 1. Supravital staining of cells from these lesions gives information unobtainable with ordinary histologic methods. 2. The scrapings show a great predominance of certain cells almost entirely devoid of phagocytic power and not characterized by the reactions with neutral red which distinguish monocytes, epithelioid cells, and clasmatocytes. Hence they differ from the essential cells of the lesions of tuberculosis and experimental syphilis. These differences are probably of a functional and developmental rather than of a genetic nature. 3. The cells probably arise from the undifferentiated mesenchymal elements of loose connective tissue, although it is possible that endothelial cells take part in their formation in some instances. 4. Since there is little doubt that the subcutaneous rheumatic nodules are pathologically identical with rheumatic granulomata else-where in the body, these conclusions are considered applicable also to the Aschoff body cells of the myocardial submiliary nodules.
Characterization of Effusion-Infiltrating T Cells
Authors: Djordje Atanackovic, Andreas Block, Andreas de Weerth, Christiane Faltz, Dieter Kurt Hossfeld, Susanna Hegewisch-Becker
Journal: Clinical Cancer Research (2004)

Abstract Purpose: While naïve T cells circulate between peripheral blood and lymph nodes, memory effector T cells acquire certain surface molecules that enable them to travel to peripheral tissues and exert their effector function. We analyzed whether deficient numbers of effector-type T cells within the malignant effusion might contribute to tumor escape from immunosurveillance. Experimental Design: We analyzed the expression of a broad range of adhesion molecules and chemokine receptors (CD62L, CD56, CCR4, CCR5, CCR7, CXCR3, CLA, and integrin α4β7) on tumor-associated lymphocytes in effusions and peripheral blood lymphocytes of patients with malignant ascites (n = 11) or malignant pleural effusion (n = 16). A tumor-associated lymphocyte:peripheral blood lymphocyte ratio was calculated as an indicator for homing of lymphocytes into the effusions and was compared with patients with nonmalignant ascites (n = 17). Results: Patients with malignancies show an increased enrichment of T cells expressing the phenotype of “naïve” (CD62L+ and CD45RA+CCR7+), “central memory” (CD45RA-CCR7+), and type 2-polarized (CCR4+) T cells within their effusions. In contrast, enrichment of “effector”-type (CD45RA-CCR7− or CD45RA+CCR7−) and presumably type 1-polarized T cells (CCR5+) at the tumor site is deficient. The same is true for natural killer cells and potentially cytotoxic CD56+ T cells. Conclusions: Here we show for the first time that patients with malignant effusions show a deficient enrichment of T cells expressing the phenotype of type-1-polarized effector T cells at the tumor site. This mechanism is likely to contribute to the escape of tumor cells from immunosurveillance.
GIT1 Mediates Thrombin Signaling in Endothelial Cells
Authors: Geerten P. van Nieuw Amerongen, Kanchana Natarajan, Guoyong Yin, Ryan J. Hoefen, M. Osawa, Judith Haendeler, A.J. Ridley, K. Fujiwara, Victor W.M. van Hinsbergh, Bradford C. Berk
Journal: Circulation Research (2004)

Thrombin mediates changes in endothelial barrier function and increases endothelial permeability. A feature of thrombin-enhanced endothelial hyperpermeability is contraction of endothelial cells (ECs), accompanied by formation of focal adhesions (FAs). Recently, a G protein-coupled receptor kinase-interacting protein, GIT1, was shown to regulate FA disassembly. We hypothesized that GIT1 modulates thrombin-induced changes in FAs. In human umbilical vein ECs (HUVECs), thrombin recruited GIT1 to FAs, where GIT1 colocalized with FAK and vinculin. Recruitment of GIT1 to FAs was dependent on activation of the small GTPase RhoA, and Rho kinase, as demonstrated by adenoviral transfection of dominant-negative RhoA and treatment with Y-27632. Thrombin stimulated GIT1 tyrosine phosphorylation with a time course similar to FAK phosphorylation in a Rho kinase- and Src-dependent manner. Depletion of GIT1 with antisense GIT1 oligonucleotides had no effect on basal cell morphology, but increased cell rounding and contraction of HUVECs, increased FA formation, and increased FAK tyrosine phosphorylation in response to thrombin, concomitant with increased endothelial hyperpermeability. These data identify GIT1 as a novel mediator in agonist-dependent signaling in ECs, demonstrate that GIT1 is involved in cell shape changes, and suggest a role for GIT1 as a negative feedback regulator that augments recovery of cell contraction.