tbuckley/cabot-search huggingface dataset:
Gene Expression Profiling of Paraffin-Embedded Primary Melanoma Using the DASL Assay Identifies Increased Osteopontin Expression as Predictive of Reduced Relapse-Free Survival
Authors: Caroline Conway, Angana Mitra, Rosalyn Jewell, Juliette Randerson-Moor, Samira Lobo, Jrmie Nsengimana, Sara Edward, D. Scott Sanders, Martin Cook, Barry Powell, Andy Boon, Faye Elliott, Floor de Kort, Margaret A. Knowles, D. Timothy Bishop, Julia Newton-Bishop
Journal: Clinical Cancer Research (2009)

Gene expression studies in melanoma have been few because tumors are small and cryopreservation is rarely possible. The purpose of this study was to evaluate the Illumina DASL Array Human Cancer Panel for gene expression studies in formalin-fixed melanoma primary tumors and to identify prognostic biomarkers.Primary tumors from two studies were sampled using a tissue microarray needle. Study 1: 254 tumors from a melanoma cohort recruited from 2000 to 2006. Study 2: 218 tumors from a case-control study of patients undergoing sentinel node biopsy.RNA was obtained from 76% of blocks; 1.4% of samples failed analysis (transcripts from <250 of the 502 genes on the DASL chip detected). Increasing age of the block and increased melanin in the tumor were associated with reduced number of genes detected. The gene whose expression was most differentially expressed in association with relapse-free survival in study 1 was osteopontin (SPP1; P = 2.11 x 10(-6)) and supportive evidence for this was obtained in study 2 used as a validation set (P = 0.006; unadjusted data). Osteopontin level in study 1 remained a significant predictor of relapse-free survival when data were adjusted for age, sex, tumor site, and histologic predictors of relapse. Genes whose expression correlated most strongly with osteopontin were PBX1, BIRC5 (survivin), and HLF.Expression data were obtained from 74% of primary melanomas and provided confirmatory evidence that osteopontin expression is a prognostic biomarker. These results suggest that predictive biomarker studies may be possible using stored blocks from mature clinical trials.
GA<sup>2</sup>LEN (Global Allergy and Asthma European Network) addresses the allergy and asthma ‘epidemic’
Authors: J. Bousquet, P. G. Burney, T. Zuberbier, P. v. Cauwenberge, C. A. Akdis, C. Bindslev‐Jensen, S. Bonini, W. J. Fokkens, F. Kauffmann, M. L. Kowalski, K. Lodrup‐Carlsen, J. Mullol, E. Nizankowska‐Mogilnicka, N. Papadopoulos, E. Toskala, M. Wickman, J. Anto, N. Auvergne, C. Bachert, P. J. Bousquet, B. Brunekreef, G. W. Canonica, K. H. Carlsen, M. Gjomarkaj, T. Haahtela, P. Howarth, G. Lenzen, J. Lotvall, K. Radon, J. Ring, M. Salapatas, H. J. Schünemann, A. Szczecklik, A. Todo‐Bom, E. Valovirta, E. Von Mutius, J. P. Zock
Journal: Allergy (2009)

Allergic diseases represent a major health problem in Europe. They are increasing in prevalence, severity and costs. The Global Allergy and Asthma European Network (GA 2 LEN), a Sixth EU Framework Program for Research and Technological Development (FP6) Network of Excellence, was created in 2005 as a vehicle to ensure excellence in research bringing together research and clinical institutions to combat fragmentation in the European research area and to tackle Allergy in its globality. The Global Allergy and Asthma European Network has benefited greatly from the voluntary efforts of researchers who are strongly committed to this model of pan‐European collaboration. The network was organized in order to increase networking for scientific projects in allergy and asthma around Europe and to make GA 2 LEN the world leader in the field. Besides these activities, research has also been carried out and the first papers are being published. Achievements of the Global Allergy and Asthma European Network can be grouped as follows: (i) those for a durable infrastructure built up during the project phase, (ii) those which are project‐related and based on these novel infrastructures, and (iii) the development and implementation of guidelines. The major achievements of GA 2 LEN are reported in this paper.
Renal Disease With Staphylococcus albus Bacteremia
Authors: Linda Rames
Journal: JAMA (1970)

Three patients had Staphylococcus albus bacteremia as a complication of ventriculoatrial shunts. Each had hematuria, proteinuria, azotemia, acidosis, and anemia; one had the nephrotic syndrome. Two patients' conditions improved after removal of infected shunts; serum complement was reduced in one. Percutaneous renal biopsies showed progressive proliferative and membranous lesions in one patient, proliferative glomerulonephritis in two. Immunofluorescent microscopy showed presence of immunoglobulin in the glomeruli of one and serum complement in two patients. Electron microscopy revealed accumulation of electron-dense, coarsely granular material within the endothelial surface of the basement membrane in all three patients. These findings suggest an immunologic process as the pathophysiologic basis for the renal lesion.
Estimating the Precursor Frequency of Naive Antigen-specific CD8 T Cells
Authors: Joseph N. Blattman, Rustom Antia, David J.D. Sourdive, Xiaochi Wang, Susan M. Kaech, Kaja Murali-Krishna, John D. Altman, Rafi Ahmed
Journal: The Journal of Experimental Medicine (2002)

The constraint of fitting a diverse repertoire of antigen specificities in a limited total population of lymphocytes results in the frequency of naive cells specific for any given antigen (defined as the precursor frequency) being below the limit of detection by direct measurement. We have estimated this precursor frequency by titrating a known quantity of antigen-specific cells into naive recipients. Adoptive transfer of naive antigen-specific T cell receptor transgenic cells into syngeneic nontransgenic recipients, followed by stimulation with specific antigen, results in activation and expansion of both donor and endogenous antigen-specific cells in a dose-dependent manner. The precursor frequency is equal to the number of transferred cells when the transgenic and endogenous responses are of equal magnitude. Using this method we have estimated the precursor frequency of naive CD8 T cells specific for the H-2Db–restricted GP33–41 epitope of LCMV to be 1 in 2 × 105. Thus, in an uninfected mouse containing ∼2-4 × 107 naive CD8 T cells we estimate there to be 100–200 epitope-specific cells. After LCMV infection these 100–200 GP33-specific naive CD8 T cells divide &amp;gt;14 times in 1 wk to reach a total of ∼107 cells. Approximately 5% of these activated GP33-specific effector CD8 T cells survive to generate a memory pool consisting of ∼5 × 105 cells. Thus, an acute LCMV infection results in a &amp;gt;1,000-fold increase in precursor frequency of DbGP33-specific CD8 T cells from 2 × 102 naive cells in uninfected mice to 5 × 105 memory cells in immunized mice.
S100A9 Is a Novel Ligand of EMMPRIN That Promotes Melanoma Metastasis
Authors: Toshihiko Hibino, Masakiyo Sakaguchi, Shoko Miyamoto, Mami Yamamoto, Akira Motoyama, Junichi Hosoi, Tadashi Shimokata, Tomonobu Ito, Ryoji Tsuboi, Nam-ho Huh
Journal: Cancer Research (2012)

The calcium-binding proteins S100A8 and S100A9 can dimerize to form calprotectin, the release of which during tissue damage has been implicated in inflammation and metastasis. However, receptor(s) mediating the physiologic and pathophysiologic effects of this damage-associated "danger signal" are uncertain. In this study, searching for candidate calprotectin receptors by affinity isolation-mass spectrometry, we identified the cell surface glycoprotein EMMPRIN/BASIGIN (CD147/BSG). EMMPRIN specifically bound to S100A9 but not S100A8. Induction of cytokines and matrix metalloproteases (MMP) by S100A9 was markedly downregulated in melanoma cells by attenuation of EMMPRIN. We found that EMMPRIN signaling used the TNF receptor-associated factor TRAF2 distinct from the known S100-binding signaling pathway mediated by RAGE (AGER). S100A9 strongly promoted migration when EMMPRIN was highly expressed, independent of RAGE, whereas EMMPRIN blockade suppressed migration by S100A9. Immunohistologic analysis of melanomas revealed that EMMPRIN was expressed at both the invasive edge of lesions and the adjacent epidermis, where S100A9 was also strongly expressed. In epidermal-specific transgenic mice, tail vein-injected melanoma accumulated in skin expressing S100A9 but not S100A8. Together, our results establish EMMPRIN as a receptor for S100A9 and suggest the therapeutic use in targeting S100A9-EMMPRIN interactions.
Hepatobiliary complications in chronic pancreatitis.
Authors: C Wilson, C D Auld, R Schlinkert, A H Hasan, C W Imrie, R N MacSween, D C Carter
Journal: Gut (1989)

Thirty nine patients undergoing surgery for chronic pancreatitis were investigated for evidence of hepatobiliary disease. In addition to pre-operative assessment by liver function tests, ultrasound, ERCP (in 33) and percutaneous transhepatic cholangiography (in five), all had peroperative liver biopsy. Common bile duct stenosis was diagnosed in 16 (62%) of the 26 patients with successful cholangiography. Features of extrahepatic biliary obstruction were found on biopsy in 11 patients, three of whom showed features of secondary sclerosing cholangitis. No patients had secondary biliary cirrhosis. Three had parenchymal liver disease (cirrhosis, resolving hepatitis and alcoholic hepatitis respectively) and two others had features suggestive of previous alcohol-induced injury. Five (83%) of the patients with clinical jaundice had biopsy features of extrahepatic biliary obstruction, as did eight (67%) with alkaline phosphatase above twice normal and seven (44%) with radiological common bile duct stenosis. Neither alkaline phosphatase rise, nor common bile duct stenosis alone or in combination, were a reliable indication of the need for biliary enteric bypass surgery. Pre-operative liver biopsy may be a valuable adjunct in the assessment of such patients.
Contralateral Second Breast Cancers: Prediction and Prevention
Authors: D. J. Brenner
Journal: JNCI Journal of the National Cancer Institute (2010)

Long-term survival after a breast cancer diagnosis has increased markedly in the last decade: 15-year relative survival in the United States is now 75% (1), up from 58% in 2001. This increase is due in part to earlier detection but also to improved treatment options (2,3). So it is highly appropriate that increasing attention is being paid to the issue of breast cancer survivorship and, in particular, the issue of second breast cancers. Several long-term studies suggest that contralateral second breast cancer rates range from 10% to 15% at 15 years after treatment and are even higher for still longerterm survivors (4,5). The risk of a breast cancer survivor developing a second breast cancer is much higher than the risk of a comparable healthy woman developing a first breast cancer. For example, a healthy 55-year-old woman has about a 2.5% chance of developing invasive cancer in a given breast over the next 15 years, whereas a 55-year-old breast cancer survivor has a 10%–15% chance of developing invasive cancer in the contralateral breast over the next 15 years. Only a small component of this disturbingly large risk of a second breast cancer is treatment related: If anything, some chemotherapy regimens may reduce the rate of second breast cancers (6), and the comparatively low and inhomogeneous dose of scattered or leakage radiation to the contralateral breast during radiotherapy (7) results in only a small increase in the risk of contralateral breast cancer (5,8–10). These considerations imply that women with breast cancer are prone to develop a second breast cancer. Lifestyle and reproductive factors (11), as well as genetic factors (12), are each presumably major players in the etiology of second breast cancers, as they are in the etiology of primary breast cancers. Thus, there has been much interest in trying to identify genes that are associated with second breast cancers. Not surprisingly, the same genes that have been linked to increased susceptibility to primary breast cancer have been the most studied with regard to susceptibility to second cancers. For example, Graeser et al. (13) investigated the risk of contralateral second breast cancer in BRCA1 and BRCA2 mutation carriers and found that women with these mutations were more likely to develop a contralateral second breast cancer compared with breast cancer survivors without these mutations. Likewise, the clinical signifi cance of mutations in the ATM gene with respect to the risk of a
Long-Term Financial Burden of Breast Cancer: Experiences of a Diverse Cohort of Survivors Identified Through Population-Based Registries
Authors: Reshma Jagsi, John A.E. Pottow, Kent A. Griffith, Cathy Bradley, Ann S. Hamilton, John Graff, Steven J. Katz, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2014)

To evaluate the financial experiences of a racially and ethnically diverse cohort of long-term breast cancer survivors (17% African American, 40% Latina) identified through population-based registries.Longitudinal study of women diagnosed with nonmetastatic breast cancer in 2005 to 2007 and reported to the SEER registries of metropolitan Los Angeles and Detroit. We surveyed 3,133 women approximately 9 months after diagnosis and 4 years later. Multivariable models evaluated correlates of self-reported decline in financial status attributed to breast cancer and of experiencing at least one type of privation (economically motivated treatment nonadherence and broader hardships related to medical expenses).Among 1,502 patients responding to both surveys, median out-of-pocket expenses were ≤ $2,000; 17% of respondents reported spending > $5,000; 12% reported having medical debt 4 years postdiagnosis. Debt varied significantly by race: 9% of whites, 15% of blacks, 17% of English-speaking Latinas, and 10% of Spanish-speaking Latinas reported debt (P = .03). Overall, 25% of women experienced financial decline at least partly attributed to breast cancer; Spanish-speaking Latinas had significantly increased odds of this decline relative to whites (odds ratio [OR], 2.76; P = .006). At least one privation was experienced by 18% of the sample; blacks (OR, 2.6; P < .001) and English-speaking Latinas (OR, 2.2; P = .02) were significantly more likely to have experienced privation than whites.Racial and ethnic minority patients appear most vulnerable to privations and financial decline attributable to breast cancer, even after adjustment for income, education, and employment. These findings should motivate efforts to control costs and ensure communication between patients and providers regarding financial distress, particularly for vulnerable subgroups.
Effective Therapy for Metastatic Renal Cancer, Whither to Now
Authors: Walter M. Stadler
Journal: Journal of Clinical Oncology (2009)

The article by Motzer et al, 1 in this issue of Journal of Clinical Oncology, reporting final survival results from the definitive trial of sunitinib versus interferon-␣ in metastatic clear cell renal cancer confirms the benefit of this agent and confirms that sunitinib is an appropriate clinical standard of care for initial therapy and the appropriate reference standard for future phase III clinical trials.Perhaps most importantly, sunitinib is representative of the vascular endothelial growth factor (VEGF) pathway inhibitor class of agents that, along with the mammalian target of rapamycin (mTOR) inhibitors, have revolutionized the treatment of renal cancer patients.With this mature data, it is perhaps instructive to review what is known, surmised, and simply speculated in this new era of renal cancer therapy.We should perhaps first analyze whether the data in the Motzer et al 1 report truly define a benefit for patients as the authors claim.In this regard, it is notable that the original primary end point for the study was progression-free survival as measured by standard radiologic imaging and Response Evaluation Criteria in Solid Tumors-based measurements.It is further notable that such measurements are completely arbitrary and have never been demonstrated to be a true surrogate end point in this disease.Thus, although there was a very dramatic improvement in progression-free survival, this alone does not prove that there was a true benefit to patients.The observed improvement in survival, which does define a patient benefit, was only borderline significant by the usual statistical criteria.Importantly, the magic P ϭ .05 is in itself somewhat arbitrary and the various statistical approaches that lead to P values either above or below this value is a set of mathematic manipulations that does not change the overall conclusion that there is a small but not vanishingly small probability that the observed differences in survival are simply due to random variation.In general, a single study with an improvement in a validated end point that is significant at an approximate P value of .05would be insufficient for regulatory authorities or clinicians to change practice.So why is this different?The authors argue that the lack of a more dramatic effect on survival is due to cross-over to sunitinib or other VEGF pathway inhibitor therapy in patients originally randomly assigned to interferon-␣.Although this is a reasonable argument, the lack of a formal cross-over process for all patients in the original protocol makes definitive conclusions difficult.Nevertheless, it is quite notable that the median survival of the control group was more than 21 months, a number that far exceeds the median survival of any prior interferon-based trial in clear cell renal cancer, and exceeded only by the 26-month survival in the sunitinib-treated group.This, along with the authors' analyses, the published data on quality-of-life
Quadriceps muscle fibre dysfunction in patients with pulmonary arterial hypertension
Authors: Emmy Manders, Gerrina Ruiter, Harm-Jan Bogaard, Ger J.M. Stienen, Anton Vonk-Noordegraaf, Frances S. de Man, Coen A.C. Ottenheijm
Journal: European Respiratory Journal (2015)

Despite improvements in disease targeted therapies, pulmonary arterial hypertension (PAH) is a progressive disease and PAH patients remain symptomatic [1]. Exercise intolerance is one of the main symptoms, which limit PAH patients in their daily life activities. Reduced exercise capacity is generally attributed to right ventricular dysfunction [1]. However, as with other cardiac and pulmonary diseases, PAH patients develop respiratory [2] and peripheral muscle [3, 4] weakness, which might also contribute to exercise intolerance. Indeed, exercise training improves exercise capacity in PAH patients and maximal oxygen consumption of PAH patients correlates with the functional decline of peripheral muscle strength [5, 6]. The underlying cause of the reduction in muscle strength is unclear. Some studies have reported muscle fibre atrophy and a shift towards more fast-twitch fatigable fibres in skeletal muscles of PAH patients [3, 7]; however, these are not consistent findings [4, 8]. Peripheral muscle weakness in PAH patients is at least partly caused by sarcomeric dysfunction <http://ow.ly/J8LuE>
INFLUENZA VIRUS INFECTION IN THE HAMSTER
Authors: William F. Friedewald, Edward W. Hook
Journal: The Journal of Experimental Medicine (1948)

A STUDY OF INFLUENZA VIRUS INFECTION IN THE HAMSTER HAS YIELDED THE FOLLOWING RESULTS: 1. Two influenza A strains (Ga. 47 and PR8) multiplied readily in the hamster lung, although no lung lesions were produced during six serial passages. On further passage both viruses abruptly acquired the capacity to produce pulmonary consolidation and death of the animals. 2. Extracts of the lungs during the early passages contained complement-fixing antigen and infectious virus, as revealed by titration in mice and embryonated eggs. Agglutinins for chicken, human, and guinea pig red cells, however, were not demonstrable at this time. With further passage a close correlation was observed between the capacity of the virus to produce lung lesions in the hamster and to agglutinate mammalian types of red cells. In addition, quantitative changes in the virus population were demonstrated in the lung extracts by complement fixation tests and titrations in mice and eggs. 3. Incubation at 37 degrees C. was effective in bringing out agglutinins in high titer for chicken red cells in lung extracts, which originally failed to agglutinate chicken cells but agglutinated mammalian red cells. This method did not increase the titers of mammalian cell agglutinins. 4. The body temperature of the hamster was found to decrease within 1 to 4 days after inoculation of influenza virus. In the early passages the temperature returned to normal within 24 hours, but with the development of the pathogenic strain of virus the temperature remained at subnormal levels until death. 5. The Lee strain of influenza B virus produced pulmonary lesions in the hamster on the first passage and no increase in pathogenicity of the virus occurred during eleven serial passages. Virus was demonstrable in extracts of the lungs by all the methods used and no difference was observed in its capacity to agglutinate fowl and mammalian types of red cells. The implications of these findings are considered briefly in the discussion.
Sustained Hypoxia Depresses Sensory Processing of Respiratory Resistive Loads
Authors: Danny J. Eckert, Peter G. Catcheside, Rachel McDonald, Amanda M. Adams, Kate E. Webster, Michael C. Hlavac, R. Doug McEvoy
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: The combination of acute hypoxia and increased respiratory load is encountered in several respiratory diseases including acute life-threatening asthma and sleep apnea. Hypoxia has been shown to inhibit respiratory load perception in healthy and asthmatic subjects, and could contribute to treatment delays and impaired function of protective reflexes.Objectives: Using respiratory-related evoked potentials (RREPs) this study aimed to determine the sensory processes mediating hypoxia-induced suppression of respiratory load sensation.Methods: EEG was measured over the central and parietal cortical regions in 14 healthy subjects. RREPs were elicited by 500-ms midinspiratory resistive load stimuli during and after isocapnic normoxia or hypoxia (blood arterial O2 saturation ∼ 80%). On a separate occasion, subjects rated the perceived magnitude of five externally applied inspiratory resistive loads (range, 8.6–43.7 cm H2O · L−1 · s) under similar experimental conditions. In both experiments subjects voluntarily ventilated approximately 90% above baseline to match ventilatory output between gas conditions.Results: RREP stimulus was matched between gas conditions in 11 subjects (minimum mask pressure −9.7 ± 0.6 versus −9.2 ± 0.4 cm H2O). P1 and P2 amplitudes were reduced during isocapnic hypoxia compared with normoxia (maximal at Cz: P1, 2.5 ± 1.1 versus 3.9 ± 1.2 μv, p = 0.03; P2, 10.0 ± 2.2 versus 12.4 ± 2.1 μv, p < 0.01, respectively). Perceived magnitude of externally applied resistive loads was also reduced during hypoxia compared with normoxia (17.1 ± 1.1 versus 19.0 ± 1.1 au, p < 0.01).Conclusions: These data confirm that isocapnic hypoxia suppresses respiratory load sensation. Decreased amplitude of the earlier (P1) RREP component suggests that this is mediated, at least in part, by suppression of respiratory afferent information before its arrival at the primary sensory cortex.