tbuckley/cabot-search huggingface dataset:
The Effects of Adrenomedullin Overexpression in Breast Tumor Cells
Authors: Alfredo Martínez, Michele Vos, Liliana Guédez, Gurmeet Kaur, Zhong Chen, Mercedes Garayoa, Rubén Pío, Terry Moody, William G Stetler-Stevenson, Hynda K Kleinman, Frank Cuttitta
Journal: JNCI Journal of the National Cancer Institute (2002)

Adrenomedullin is a secreted peptide hormone with multiple activities. Several reports have indicated that adrenomedullin may be involved in tumor survival, but this has not been directly shown. Here we evaluate the in vitro and in vivo effects of adrenomedullin overexpression in human breast cancer cells.The human breast cancer cell lines T47D and MCF7, both of which express low basal levels of adrenomedullin, were stably transfected with an expression construct that contained the coding region of the human adrenomedullin gene or with empty expression vector. Properties of the transfected cells were assessed by proliferation and apoptosis assays, in vitro and in vivo angiogenesis assays, cell migration experiments, and xenograft implants. The effect of synthetic adrenomedullin on human ovarian (ECV) cancer cell motility was also tested. Western blot analysis was used to compare expression levels of several genes whose products are associated with cell growth and regulation of apoptosis.T47D and MCF7 cells transfected with the adrenomedullin construct both expressed high levels of adrenomedullin mRNA and protein. Compared with cells transfected with empty vector, cells that overexpressed adrenomedullin displayed a more pleiotropic morphology, an increased angiogenic potential both in vitro and in vivo, and less apoptosis after serum deprivation. T47D and MCF7 cells did not display measurable motility, but ECV ovarian cancer cells treated with synthetic adrenomedullin were more motile than saline-treated ECV cells. Adrenomedullin-overexpressing T47D cells had higher levels of proteins involved in oncogenic signal transduction pathways (such as Ras, Raf, PKC, and MAPKp49) and lower levels of pro-apoptotic proteins (such as Bax, Bid, and caspase 8) than T47D cells transfected with empty vector. In a preliminary in vivo experiment, three of 10 nude mice injected with adrenomedullin-overexpressing T47D cells developed xenograft tumors, whereas none of the 10 nude mice injected with cells carrying the empty plasmid developed tumors.These results further support the role of adrenomedullin as a survival factor for tumors. Development of physiologically efficient inhibitors of adrenomedullin may prove useful in the clinical management of cancer.
Intelectin 1 suppresses the growth, invasion and metastasis of neuroblastoma cells through up-regulation of N-myc downstream regulated gene 2
Authors: Dan Li, Hong Mei, Jiarui Pu, Xuan Xiang, Xiang Zhao, Hongxia Qu, Kai Huang, Liduan Zheng, Qiangsong Tong
Journal: Molecular Cancer (2015)

Recent studies have revealed the potential roles of intelectin 1 (ITLN1) in tumorigenesis. However, its functions and underlying mechanisms in neuroblastoma (NB), the most common extracranial solid tumor in childhood, still remain largely unknown.Human neuroblastoma cell lines were treated with recombinant ITLN1 protein or stably transfected with ITLN1 expression and short hairpin RNA vectors. Gene expression and signaling pathway were detected by western blot and real-time quantitative RT-PCR. Gene promoter activity and transcription factor binding were detected by luciferase reporter and chromatin immunoprecipitation assays. Growth and aggressiveness of tumor cells were measured by MTT colorimetry, colony formation, scratch assay, matrigel invasion assay, and nude mice model.Mining of public microarray databases revealed that N-myc downstream regulated gene 2 (NDRG2) was significantly correlated with ITLN1 in NB. Gain- and loss-of-function studies indicated that secretory ITLN1 facilitated the NDRG2 expression, resulting in down-regulation of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9), in NB cell lines SH-SY5Y, SK-N-BE(2), and SK-N-SH. Krüppel-like factor 4 (KLF4), a transcription factor crucial for NDRG2 expression, was up-regulated by ITLN1 in NB cells via inactivation of phosphoinositide 3-kinase (PI3K)/AKT signaling. Ectopic expression of ITLN1 suppressed the growth, invasion and metastasis of NB cells in vitro and in vivo. Conversely, knockdown of ITLN1 promoted the growth, invasion, and metastasis of NB cells. In addition, rescue experiments in ITLN1 over-expressed or silenced NB cells showed that restoration of NDRG2 expression prevented the tumor cells from ITLN1-mediated changes in these biological features. In clinical NB tissues, ITLN1 was down-regulated and positively correlated with NDRG2 expression. Patients with high ITLN1 or NDRG2 expression had greater survival probability.These findings indicate that ITLN1 functions as a tumor suppressor that affects the growth, invasion and metastasis of NB through up-regulation of NDRG2.
INTERMEDIATE TERM OUTCOMES IN PATIENTS WITH INTERRUPTED AORTIC ARCH
Authors: Michael O'Byrne, Laura Mercer-Rosa, Huaqing Zhao, Xuemei Zhang, Ronn Tanel, Bradley Marino, Amy Cassedy, Mark Fogel, Jack Rychik, Wei Yang, Stephen Paridon, Elizabeth Goldmuntz
Journal: Journal of the American College of Cardiology (2013)
Efficacy of screening donors for antibodies to the hepatitis C virus to prevent transfusion-associated hepatitis: Final report of a prospective trial
Authors: Antonio González, Juan I. Esteban, Pedro Madoz, Luis Viladomiu, Juan Genesca, Eduardo Muñiz, Jaime Enríquez, Xavier Torras, José M. Hernández, Josep Quer, Xavier Vidal, Harvey J. Alter, James W. Shih, Rafael Esteban, Jaime Guardia
Journal: Hepatology (1995)

Routine screening of blood donors for anti-hepatitis C virus (HCV) has been implemented in most developed countries. However, the independent efficacy of such screening has not been established in a controlled, prospective study. We tracked 478 patients transfused with anti-HCV-negative blood by first-generation enzyme-linked immunoassay (EIA) between July 1989 and May 1990 and compared the incidence of transfusion-associated hepatitis and HCV infections with that found among 280 patients transfused with blood unscreened for anti-HCV during the immediately preceding year. Of the 280 patients who had received transfusions before donors were screened for anti-HCV, 27 (9.6%) developed posttransfusion hepatitis and 1 additional patient sero-converted to anti-HCV without evidence of hepatitis, for a risk of posttransfusion HCV infection of 10.7% (28 of 262 recipients seronegative for anti-HCV before transfusion). Of the 478 patients transfused after July 1989 with blood screened for anti-HCV, only 9 (1.9%) developed posttransfusion hepatitis for a risk reduction of 80%. Seven of the 9 residual cases of hepatitis were caused by HCV (7 of 456 recipients seronegative before transfusion or 1.5%) for a risk reduction of transfusion-associated HCV infection of 86%. In retrospect, an anti-HCV positive donor was detected by second-generation immunoassay in 4 (57%) of the 7 HCV cases from the study cohort and in 19 of the 23 (83%) cases from whom all donor samples were available for testing in the historical cohort. No additional infectious donors were detected by third-generation immunoassay or serum HCV-RNA by polymerase chain reaction. Implementation of donor screening for anti-HCV with a first-generation immunoassay appeared to be independently associated with an 80% and 86% reduction in the risks of transfusion-associated hepatitis and HCV infection, respectively. Screening of donors with second-generation immunoassays might have further reduced the risk by 57%. An additional 0.4% may be at risk of developing non-A, non-B, non-C hepatitis. (Hepatology 1995;22:439-445.)
Adrenal Suppression And Cushing's Syndrome Due To The Interaction Between Ritonavir And Inhaled Fluticasone
Authors: D. Elbirt, K. Mahlev-Guri, S. Gradstein, A. Zung, I. Asher, B. Werner, S. Radain-Sade, M. Burke, Z.M. Sthoeger
Journal: Journal of Allergy and Clinical Immunology (2010)
Regulation and Functions of the IL-10 Family of Cytokines in Inflammation and Disease
Authors: Wenjun Ouyang, Sascha Rutz, Natasha K. Crellin, Patricia A. Valdez, Sarah G. Hymowitz
Journal: Annual Review of Immunology (2011)

The IL-10 family of cytokines consists of nine members: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, and the more distantly related IL-28A, IL-28B, and IL-29. Evolutionarily, IL-10 family cytokines emerged before the adaptive immune response. These cytokines elicit diverse host defense mechanisms, especially from epithelial cells, during various infections. IL-10 family cytokines are essential for maintaining the integrity and homeostasis of tissue epithelial layers. Members of this family can promote innate immune responses from tissue epithelia to limit the damage caused by viral and bacterial infections. These cytokines can also facilitate the tissue-healing process in injuries caused by infection or inflammation. Finally, IL-10 itself can repress proinflammatory responses and limit unnecessary tissue disruptions caused by inflammation. Thus, IL-10 family cytokines have indispensable functions in many infectious and inflammatory diseases.
A peripheral CD4+ T cell precursor for naive, memory, and regulatory T cells
Authors: Chunfang Zhao, Joanna D. Davies
Journal: The Journal of Experimental Medicine (2010)

Mechanisms that control the size of the T cell pool, the ratio between naive cells and memory cells, the number and frequency of regulatory T cells, and T cell receptor (TCR) diversity are necessary to maintain immune integrity and avoid disease. We have previously shown that a subset of naive CD4+ T cells, defined by the expression on their surface of a very low density of CD44 (CD44v.low cells), can inhibit wasting and wasting-associated lymphopenia in mice with cancer. In this study, we further investigate the properties of CD44v.low cells and show that they are significantly more efficient than the remaining naive (CD44low or CD44int) and memory CD4+ cell subsets in reconstituting the overall size of the CD4+ T cell pool, creating a T cell pool with a diverse TCR repertoire, generating regulatory T cells that express forkhead box P3 (FoxP3), and promoting homeostatic equilibrium between naive, memory, and Foxp3+ regulatory T cell numbers. T cell population reconstitution by CD44v.low cells is thymus independent. Compared with CD44int cells, a higher percentage of CD44v.low cells express B cell leukemia/lymphoma 2, interleukin-7 receptor, and CD5. The data support a key role for CD4+ CD44v.low cells as peripheral precursors that maintain the integrity of the CD4+ T cell pool.
Aspergillus laryngotracheobronchitis presenting as stridor in a patient with peripheral T cell lymphoma.
Authors: P. H. Kuo, L. N. Lee, P. C. Yang, Y. C. Chen, K. T. Luh
Journal: Thorax (1996)

Invasive aspergillosis is a serious opportunistic infection in immunocompromised patients. The case history is described of a 44 year old patient with peripheral T cell lymphoma who developed hoarseness and stridor after chemotherapy. Aspergillus fumigatus was isolated repeatedly from the sputum. Bronchoscopic examination showed symmetrical creamy-white exophytic lesions involving both vocal cords and the supraglottic area. There was diffuse tracheobronchitis with multiple raised cream-coloured plaques in the trachea which histologically consisted of numerous septate branching hyphae consistent with Aspergillus species. The lesions responded to systemic treatment with amphotericin B.
Maximum-Likelihood Analysis of Molecular Adaptation in Abalone Sperm Lysin Reveals Variable Selective Pressures Among Lineages and Sites
Authors: Z Yang, W J Swanson, V D Vacquier
Journal: Molecular Biology and Evolution (2000)

Maximum-likelihood models of codon substitution were used to analyze sperm lysin genes of 25 abalone (Haliotis) species to identify lineages and amino acid sites under diversifying selection. The models used the nonsynonymous/synonymous rate ratio (ω = dN/dS) as an indicator of selective pressure and allowed the ratio to vary among lineages or sites. Likelihood ratio tests suggested significant variation in selective pressure among lineages. The variable selective pressure provided an explanation for the previous observation that the ω ratio is >1 in comparisons of closely related species and <1 in comparisons of distantly related species. Computer simulations demonstrated that saturation of nonsynonymous substitutions and constraint on lysin structure were unlikely to account for the observed pattern. Lineages linking closely related sympatric species appeared to be under diversifying selection, while lineages separating distantly related species from different geographic locations were associated with low evolutionary rates. The selective pressure indicated by the ω ratio was found to vary greatly among amino acid sites in lysin. Sites under potential diversifying selection were identified. Ancestral lysins were inferred to trace the route of evolution at individual sites and to provide lysin sequences for future laboratory studies.
A Transplantable Leukemia From Mice Inoculated With Rauscher Leukemia Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T. N. Fredrickson, Joseph LoBue, Peter A. Alexander, Jr., Edward F. Schultz, A. S. Gordon
Journal: JNCI Journal of the National Cancer Institute (1972)

If given in relatively high dilutions, Rauscher leukemia virus (RLV) induced chronic leukemia in intact BALB/c mice. Greater doses of RLV induced splenic destruction and early death. The chronic leukemias were characterized by wasting, anemia, large numbers of erythroid and/or myeloid precursors in the peripheral blood, splenomegaly, and hepatomegaly. There was no lymphoproliferative involvement of the lymph nodes, thymus, or splenic white pulp. Thus induction of myelogenous leukemia appears to be part of the oncogenic spectrum of RLV. The truly neoplastic nature of the chronic disease was illustrated by successful isogeneic transplantation of leukemic cells in 4 cases by intravenous inoculation of recipients. One such transplantable leukemia served as the source material for a continuous transplant line of myelomonocytoid cells. Plasma derived from mice bearing the transplantable leukemia induced a chronic disease in BALB/c mice involving erythroid precursors.
LYSOSOMAL ACID HYDROLASES IN MICE INFECTED WITH BCG
Authors: Kazuhisa Saito, Emanuel Suter
Journal: The Journal of Experimental Medicine (1965)

Experiments are reported dealing with the increase of lysosomal acid hydrolases induced by BCG infection. Acid hydrolases were determined quantitatively in peritoneal MP, liver homogenate, and plasma of normal and BCG-infected mice. A significant increase of acid phosphatase, beta-glucuronidase, and cathepsin was found in MP and liver homogenate of BCG-infected mice. In plasma also a significant increase of acid phosphatase and beta-glucuronidase was noticed. The results of the determination of the enzymes in centrifugally separated subcellular fractions of liver homogenate indicated clearly that the acid hydrolases associated mainly with the "large granular" fraction, which consists of mitochondria, lysosomes, and microsomes and that infection with BCG caused significant increase of the enzymes specifically in this fraction. Differences in the pattern of location among centrifugally separated fraction of liver homogenate were observed between acid phosphatase and the other two acid hydrolases. MP cultured in vitro doubled their acid phosphatases content within 24 hours, whereas beta-glucuronidase rather decreased in the same cells.
External Validation of the UKPDS Risk Engine in Incident Type 2 Diabetes: A Need for New Type 2 Diabetes–Specific Risk Equations
Authors: Christian A. Bannister, Chris D. Poole, Sara Jenkins-Jones, Christopher Ll. Morgan, Glyn Elwyn, Irena Spasić, Craig J. Currie
Journal: Diabetes Care (2013)

OBJECTIVE To evaluate the performance of the UK Prospective Diabetes Study Risk Engine (UKPDS-RE) for predicting the 10-year risk of cardiovascular disease end points in an independent cohort of U.K. patients newly diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS This was a retrospective cohort study using routine health care data collected between April 1998 and October 2011 from ∼350 U.K. primary care practices contributing to the Clinical Practice Research Datalink (CPRD). Participants comprised 79,966 patients aged between 35 and 85 years (388,269 person-years) with 4,984 cardiovascular events. Four outcomes were evaluated: first diagnosis of coronary heart disease (CHD), stroke, fatal CHD, and fatal stroke. RESULTS Accounting for censoring, the observed versus predicted 10-year event rates were as follows: CHD 6.1 vs. 16.5%, fatal CHD 1.9 vs. 10.1%, stroke 7.0 vs. 10.1%, and fatal stroke 1.7 vs. 1.6%, respectively. The UKPDS-RE showed moderate discrimination for all four outcomes, with the concordance index values ranging from 0.65 to 0.78. CONCLUSIONS The UKPDS stroke equations showed calibration ranging from poor to moderate; however, the CHD equations showed poor calibration and considerably overestimated CHD risk. There is a need for revised risk equations in type 2 diabetes.
Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): survival outcomes of an open-label, non-inferiority, randomised controlled trial
Authors: Seung-Yong Jeong, Ji Won Park, Byung Ho Nam, Sohee Kim, Sung-Bum Kang, Seok-Byung Lim, Hyo Seong Choi, Duck-Woo Kim, Hee Jin Chang, Dae Yong Kim, Kyung Hae Jung, Tae-You Kim, Gyeong Hoon Kang, Eui Kyu Chie, Sun Young Kim, Dae Kyung Sohn, Dae-Hyun Kim, Jae-Sung Kim, Hye Seung Lee, Jee Hyun Kim, Jae Hwan Oh
Journal: The Lancet Oncology (2014)
Synthesis of myosin heavy and light chains in the afterloaded guinea pig right ventricle
Authors: C. EVANS, S. S. SCHREIBER, M. ORATZ, M. A. ROTHSCHILD
Journal: Cardiovascular Research (1978)

Increased afterload causes increased cardiac myosin synthesis and ultimately leads to hypertrophy. Since the latter is associated with altered myosin ATPase activity, it was of interest to study the synthesis of myosin subunits in the acute response to this stress. An in vitro guinea pig heart preparation was used which allowed application of afterload to the right ventricle with unaltered coronary flow, and also permitted measurement of synthesis of myosin heavy chains (HC) and combined light chains (LC) by continuous perfusion with labelled amino acids (3H-lysine and/or 3H-phenylalanine) of constant specific activity. Isolation of 3H-labelled HC and LC with heterologous unlabelled carrier was possible because of identical mobilities of HC's and LC's from unlabeled lamb carrier myosin and 3H-labelled guinea pig myosin. This permitted study of comparative synthesis of the HC and LC in small samples as the single guinea pig right ventricle (100-150 mg) and avoided errors inherent in pooling hearts or in measurement of turnover in the non-steady state. After 3 h of perfusion, the ratio of synthesis of HC/LC was 2 : 1 in controls. This ratio increased significantly to 3 : 1 in afterload. It is possible that the disproportionate increase in HC synthesis may lead to stoichiometric problems in myosin assembly which ultimately effect altered myosin ATPase activity.
Thalidomide in the treatment of recurrent necrotic mucocutaneous aphthae
Authors: N. Kürkçüoǧlu, N. Atakan, M. Eksioǧlu
Journal: British Journal of Dermatology (2006)

Journal Article Thalidomide in the treatment of recurrent necrotic mucocutaneous aphthae Get access N. Kürkçüoǧlu, N. Kürkçüoǧlu Department of Dermatology, Hacettepe Medical School, Ankara, Turkey Search for other works by this author on: Oxford Academic Google Scholar N. Atakan, N. Atakan Department of Dermatology, Hacettepe Medical School, Ankara, Turkey Search for other works by this author on: Oxford Academic Google Scholar M. Eksioǧlu M. Eksioǧlu Department of Dermatology, Hacettepe Medical School, Ankara, Turkey Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 112, Issue 5, 1 May 1985, Page 632, https://doi.org/10.1111/j.1365-2133.1985.tb15281.x Published: 01 May 1985
Allergic <i>vs</i> nonallergic asthma: what makes the difference?
Authors: S. Romanet‐Manent, D. Charpin, A. Magnan, A. Lanteaume, D. Vervloet
Journal: Allergy (2002)

Background: The aim of this work was to describe clinical similarities and differences between allergic and nonallergic asthmatics, notably concerning the nasosinusal involvement. Methods: A total of 165 asthmatics (122 allergics and 43 nonallergics) and 193 controls (40 allergics and 153 nonallergics), recruited in the frame of EGEA study (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy), were included. Asthmatics were included on the basis of positive answer to four standardized items. To establish differences and similarities between allergic and nonallergic asthmatics, general characteristics (age, sex, smoking habits, history of hay fever and allergic dermatitis), history of asthma, severity and nasosinusal involvement were examined. Clinical assessment was based on the answers to a detailed questionnaire, and spirometry. Results: Greater age, female sex, sinusal polyposis, and FEV 1 below 80% of the predicted value increased the risk of displaying a nonallergic type of asthma, whereas history of hay fever, seasonal exacerbation of asthma, and asthma duration lowered this risk. Unexpectedly, we found no difference in terms of rhinitic symptoms between both groups, probably resulting from distinct causes. Conclusion: These results give new insights into the contrasts between clinical features of allergic and nonallergic asthma. The terminology of extrinsic asthma was first introduced by Rackeman in 1947 (1) and referred to the triggering role of allergens in asthma. By symmetry, he described intrinsic asthma as a disease characterized by later onset in life, female predominance, higher degree of severity, and more frequent association to nasosinusal polyposis. As these asthmatics were not improved by conventional treatment, this author considered their disease as caused by a nonallergic, unknown phenomenon. It is now widely admitted that nonallergic asthma can be objectively distinguished from allergic asthma based on negative skin tests to usual aeroallergens. On the other hand, positive skin test shows a tendency to produce IgE antibodies in response to low doses of allergens. “Atopy” and “atopic” are the terms used to describe this clinical trait and predisposition (2). Allergic clinical manifestations of atopy are of various types, for example rhinitis and asthma. Nowadays the terminology of “extrinsic” and “intrinsic” asthma should no longer be used, and should be replaced by the terminology of “allergic” or “nonallergic” asthma (2).
Stressing the Development of Small Molecules Targeting HSP90
Authors: Len Neckers, Jane B. Trepel
Journal: Clinical Cancer Research (2013)

Inhibitors of the molecular chaperone HSP90 have been in clinical development as anticancer agents since 1999. Recent clinical studies, including the work of Saif and colleagues in this issue of Clinical Cancer Research, demonstrate that significant progress has been made in overcoming the obstacles preventing regulatory approval.
A causal framework for integrating learning and reasoning
Authors: David A. Lagnado
Journal: Behavioral and Brain Sciences (2009)

Abstract Can the phenomena of associative learning be replaced wholesale by a propositional reasoning system? Mitchell et al. make a strong case against an automatic, unconscious, and encapsulated associative system. However, their propositional account fails to distinguish inferences based on actions from those based on observation. Causal Bayes networks remedy this shortcoming, and also provide an overarching framework for both learning and reasoning. On this account, causal representations are primary, but associative learning processes are not excluded a priori.