tbuckley/cabot-search huggingface dataset:
Processing optimization of exhaled breath condensate previous to the analysis by mass spectrometry
Authors: Laura Nunez-Naveira, Luis Marinas-Pardo, Beatríz Lema-Costa, Ninoska Flores-Calle, Héctor Verea-Hernando, Carmen Montero-Martínez
Journal: European Respiratory Journal (2012)

The Exhaled Breath Condensate (EBC) is a representative and non-invasive lung sample so the determination of its proteome might be useful to find disease-specific biomarkers. Most of the works published up to the date about this issue describe several problems to identify proteins by mass spectrometry.   Aims:  To evaluate three methods of EBC concentration as a pre-processing step for the use of mass spectrometry protein identification. To optimize the storage conditions for the EBC.   Methods:  EBC samples were collected with the EcoScreen Device (Viasys GmbH, Germany) and stored at -80°C. Protein quantification was performed by BCA methodology. Sample concentration was performed by liofilization, centrifugation with Amicon Ultra-2 filters (Millipore) or Reverse phase chromatography with POROS R2 resin. Proteins were identified by mass spectrometry.   Results:  After processing, there were no differences between liofilization and filtration which yielded an insufficient concentration for mass spectrometry (64.38±25.97; average μg/mL±standard deviation). Protein purification with POROS R2 followed by tryptic digestion gave place to the identification of 13 proteins. Long term storage of EBC affected dramatically the protein stability.   Discussion:  Protein concentration by reverse phase chromatography is necessary to determinate the EBC proteome by mass spectrometry. EBC samples should be analyzed within one year period to avoid protein degradation. This optimization is crucial to determinate the protein profile in EBC samples from different respiratory pathologies.
Association Between the Medicare Modernization Act of 2003 and Patient Wait Times and Travel Distance for Chemotherapy
Authors: Alisa M. Shea
Journal: JAMA (2008)

The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) altered reimbursements for outpatient chemotherapy drugs and drug administration services. Anecdotal reports suggest that these adjustments may have negatively affected access to chemotherapy for Medicare beneficiaries.To compare patient wait times and travel distances for chemotherapy before and after the enactment of the MMA.Analysis of a nationally representative 5% sample of claims from the Centers for Medicare & Medicaid Services for the period 2003 through 2006. Patients were Medicare beneficiaries with incident breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma who received chemotherapy in inpatient hospital, institutional outpatient, or physician office settings.Days from incident diagnosis to first chemotherapy visit and distance traveled for treatment, controlling for age, sex, race/ethnicity, cancer type, geographic region, comorbid conditions, and year of diagnosis and treatment.There were 5082 incident cases of breast cancer, colorectal cancer, leukemia, lung cancer, or lymphoma in 2003; 5379 cases in 2004; 5116 cases in 2005; and 5288 cases in 2006. Approximately 70% of patients received treatment in physician office settings in each year. Although the distribution of treatment settings in 2004 and 2005 was not significantly different from 2003 (P = .24 and P = .72, respectively), there was a small but significant change from 2003 to 2006 (P = .02). The proportion of patients receiving chemotherapy in inpatient settings decreased from 10.2% in 2003 to 8.8% in 2006 (P = .03), and the proportion in institutional outpatient settings increased from 21.1% to 22.5% (P = .004). The proportion in physician offices remained at 68.7% (P = .29). The median time from diagnosis to initial chemotherapy visit was 28 days in 2003, 27 days in 2004, 29 days in 2005, and 28 days in 2006. In multivariate analyses, average wait times for chemotherapy were 1.96 days longer in 2005 than in 2003 (95% confidence interval [CI], 0.11-3.80 days; P = .04) but not significantly different in 2006 (0.88 days; 95% CI, -0.96 to 2.71 days; P = .35). Median travel distance was 7 miles (11.2 km) in 2003 and 8 miles (12.8 km) in 2004 through 2006. After adjustment, average travel distance remained slightly longer in 2004 (1.47 miles [2.35 km]; 95% CI, 0.87-2.07 miles [1.39-3.31 km]; P < .001), 2005 (1.19 miles [1.90 km]; 95% CI, 0.58-1.80 miles [0.93-2.88 km]; P < .001), and 2006 (1.30 miles [2.08 km]; 95% CI, 0.69-1.90 miles [1.10-3.04 km]; P < .001) compared with 2003.There have not been major changes in travel distance and patient wait times for chemotherapy in the Medicare population since 2003, the year before MMA-related changes in reimbursement.
Inhibitory Effect of Calcium Antagonists on Histamine Release from Human Leukocytes
Authors: Carsten Jensen, Per Stahl Skov, Svend Norn
Journal: Allergy (1983)

A study was made of the influence of calcium antagonists on human basophil histamine release induced in vitro by specific antigen, anti‐IgE or the calcium ionophore A23187. Both verapamil, nifedipine, and nimodipine were found to inhibit the release, and a similar effect was also observed after peroral administration of verapamil and nifedipine. The inhibitory effect of the drugs on histamine release seems to depend on interaction with calcium at different sites. The anti‐allergic effect might explain the improvement found with calcium antagonists in exercise‐induced asthma.
Localization of CYP1A1 and CYP1A2 messenger RNA in normal human liver and in hepatocellular carcinoma byin situ hybridization
Authors: Ross A. McKinnon, Pauline de la M. Hall, Linda C. Quattrochi, Robert H. Tukey, Michael E. McManus
Journal: Hepatology (1991)

To better characterize the precise cellular distribution of CYP1A gene products in man, we have undertaken Northern-blot and in situ hybridization analyses of CYP1A expression in human liver. Using riboprobes transcribed from both CYP1A1 and CYP1A2 complementary DNAs to probe a series of Northern blots of 23 human liver messenger RNA samples, CYP1A1 expression was demonstrated in 11 samples and CYP1A2 expression was evident in 22 samples. The level of expression of both CYP1A enzymes in these livers demonstrated marked variability. The CYP1A1 and CYP1A2 riboprobes were then used for in situ hybridization localization of CYP1A1/1A2 messenger RNA sequences on paraffin-embedded, formalin-fixed human liver sections. These studies demonstrated that both CYP1A1 and CYP1A2 messenger RNAs are distributed nonuniformly across the human liver acinus, with levels highest in hepatocytes surrounding terminal hepatic venules and intercalated veins. Immunohistochemistry with an anti-rabbit CYP1A1 serum demonstrated a corresponding distribution for the translated CYP1A proteins. In situ hybridization analysis was also performed on sections of hepatocellular carcinoma, demonstrating a significant down-regulation in CYP1A expression. Functional studies using the activation of the food-derived heterocyclic amine MeIQ (2-amino-3,4-dimethylimadazo [4,5-f] quinoline) to a mutagen in the Ames test as an indicator of CYP1A expression confirmed this down-regulation. These results demonstrate heterogeneity of hepatic CYP1A expression both between individuals and in different acinar zones. This variation in expression may be of significance in assessing cell specific toxicities of various drugs and carcinogens.
Induction of vascular leakage through release of bradykinin and a novel kinin by cysteine proteinases from <i>Staphylococcus aureus </i>
Authors: Takahisa Imamura, Sumio Tanase, Grzegorz Szmyd, Andrzej Kozik, James Travis, Jan Potempa
Journal: The Journal of Experimental Medicine (2005)

Staphylococcus aureus is a major pathogen of gram-positive septic shock and frequently is associated with consumption of plasma kininogen. We examined the vascular leakage (VL) activity of two cysteine proteinases that are secreted by S. aureus. Proteolytically active staphopain A (ScpA) induced VL in a bradykinin (BK) B2-receptor–dependent manner in guinea pig skin. This effect was augmented by staphopain B (SspB), which, by itself, had no VL activity. ScpA also produced VL activity from human plasma, apparently by acting directly on kininogens to release BK, which again was augmented significantly by SspB. Intravenous injection of ScpA into a guinea pig caused BK B2-receptor–dependent hypotension. ScpA and SspB together induced the release of leucyl-methionyl-lysyl-BK, a novel kinin with VL and blood pressure–lowering activities that are equivalent to BK. Collectively, these data suggest that production of BK and leucyl-methionyl-lysyl-BK by staphopains is a new mechanism of S. aureus virulence and bacterial shock. Therefore, staphopain-specific inhibitors and kinin-receptor antagonists could be used to treat this disease.
The flow dependency of Tie2 expression in endotoxemia
Authors: Neng F. Kurniati, Rianne M. Jongman, Franziska vom Hagen, Katherine C. Spokes, Jill Moser, Erzsébet Ravasz Regan, Guido Krenning, Jan-Renier A. J. Moonen, Martin C. Harmsen, Michel M. R. F. Struys, Hans-Peter Hammes, Jan G. Zijlstra, William C. Aird, Peter Heeringa, Grietje Molema, Matijs van Meurs
Journal: Intensive Care Medicine (2013)
Immunohistological detection of interleukin 1-like molecules and tumour necrosis factor in human epidermis before and after UVB-irradiation in vivo
Authors: ANNEMETTE OXHOLM, P. OXHOLM, B. STABERG, K. BENDTZEN
Journal: British Journal of Dermatology (1988)

Journal Article Immunohistological detection of interleukin 1‐like molecules and tumour necrosis factor in human epidermis before and after UVB‐irradiation in vivo Get access ANNEMETTE OXHOLM, ANNEMETTE OXHOLM Department of Dermatology, Gentofte Hospital, Copenhagen, Denmark.Pathological‐anatomical Institute, Kommunehospitalet, Copenhagen, Denmark. Annemette Oxholm, MD, Department of Dermatology, Gentofte Hospital, Niels Andersensvej 65, DK‐2900 Hellerup, Denmark. Search for other works by this author on: Oxford Academic Google Scholar P. OXHOLM, P. OXHOLM Laboratory of Medical Immunology 7544, Rigshospitalet, University Hospital, Copenhagen, Denmark.Pathological‐anatomical Institute, Kommunehospitalet, Copenhagen, Denmark. Search for other works by this author on: Oxford Academic Google Scholar B. STABERG, B. STABERG Department of Dermatology, Gentofte Hospital, Copenhagen, Denmark. Search for other works by this author on: Oxford Academic Google Scholar K. BENDTZEN K. BENDTZEN Laboratory of Medical Immunology 7544, Rigshospitalet, University Hospital, Copenhagen, Denmark. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 118, Issue 3, 1 March 1988, Pages 369–376, https://doi.org/10.1111/j.1365-2133.1988.tb02430.x Published: 01 March 1988
Sunitinib Malate for the Treatment of Pancreatic Neuroendocrine Tumors
Authors: Eric Raymond, Laetitia Dahan, Jean-Luc Raoul, Yung-Jue Bang, Ivan Borbath, Catherine Lombard-Bohas, Juan Valle, Peter Metrakos, Denis Smith, Aaron Vinik, Jen-Shi Chen, Dieter Hörsch, Pascal Hammel, Bertram Wiedenmann, Eric Van Cutsem, Shem Patyna, Dongrui Ray Lu, Carolyn Blanckmeister, Richard Chao, Philippe Ruszniewski
Journal: New England Journal of Medicine (2011)

The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models and phase 1 and 2 trials.
Activation of endogenous factor V by a homocysteine-induced vascular endothelial cell activator.
Authors: G M Rodgers, W H Kane
Journal: Journal of Clinical Investigation (1986)

Vascular endothelium possesses multiple procoagulant properties, including synthesis and expression of Factor V. We studied the effects of homocysteine on the regulation of endothelial cell Factor V activity. Elevated levels of homocysteine are associated with the congenital thrombotic disorder homocystinuria. Treatment of cultured endothelial cells with 0.5-10 mM homocysteine had no effect on cell morphology, but did increase Factor V activity and prothrombin activation by Factor Xa. A radioimmunoassay for endothelial cell Factor V demonstrated that homocysteine treatment did not increase Factor V antigen levels. 125I-prothrombin was activated by treated endothelial cells and Factor Xa in the presence of thrombin inhibitors. Exogenous 125I-Factor V was cleaved by homocysteine-treated but not control endothelial cells. 125I-Factor V cleavage products distinct from those generated by thrombin and Factor Xa were identified. These data provide evidence for regulation of endothelial cell Factor V activity, and indicate that increased Factor V activity associated with homocysteine-treated vascular endothelium results primarily from induction of an activator of Factor V.
EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients
Authors: F. Cappuzzo, G. Finocchiaro, E. Rossi, P.A. Jänne, C. Carnaghi, C. Calandri, K. Bencardino, C. Ligorio, F. Ciardiello, T. Pressiani, A. Destro, M. Roncalli, L. Crino, W.A. Franklin, A. Santoro, M. Varella-Garcia
Journal: Annals of Oncology (2007)
Metastatic Pancreatic Adenocarcinoma Presenting as a Large Pelvic Mass Mimicking Primary Osteogenic Sarcoma: A Series of Two Patient Cases
Authors: Nicholas P. Webber, Sunil Sharma, Allie H. Grossmann, Akram Shaaban, Kevin B. Jones, Lester J. Layfield, R. Lor Randall
Journal: Journal of Clinical Oncology (2010)

Osteogenic sarcoma (ie, osteosarcoma) classically presents as a painful destructive lesion in bone with a large associated soft tissue mass. It has a range of appearances on plain radiographs based on the volume of boney destruction and degree of mineralization within the lesion.1 It is pathologically defined by the production of osteoid matrix by malignant cells. This predilection for bone formation is often apparent on imaging. Although periosteal reactive bone formation in response to a number of aggressive neoplasms and infections can vary in appearance, consistent mineralized bone formation throughout the substance of a mass is considered nearly pathognomonic for osteosarcoma. To our knowledge, there is no case report of a patient presenting initially with a metastasis from pancreatic adenocarcinoma to bone resulting in a large osteogenic mass mimicking osteosarcoma. Although the pelvic girdle has been shown to be a location of skeletal metastases after treatment with surgery and systemic therapy in adenocarcinoma, it is rare for pain resulting from a large osteogenic mass to be the initial presenting symptom.2
A Phase I Trial of TNFerade Biologic in Patients with Soft Tissue Sarcoma in the Extremities
Authors: Arno J. Mundt, Srinivasan Vijayakumar, John Nemunaitis, Alan Sandler, Herbert Schwartz, Nader Hanna, Terrence Peabody, Neil Senzer, Karen Chu, Camilla S. Rasmussen, Paul D. Kessler, Henrik S. Rasmussen, Michael Warso, Donald W. Kufe, Tapas Das Gupta, Ralph R. Weichselbaum
Journal: Clinical Cancer Research (2004)

Abstract Purpose: TNFerade is a second-generation replication-deficient adenovector carrying a transgene encoding human tumor necrosis factor α under control of a radiation- induced promoter. The objective of this study was to assess the tolerance of combining TNFerade and radiation therapy in patients with soft tissue sarcomas of the extremity. Experimental Design: TNFerade was administered in combination with single-daily fractionated radiation therapy in 14 patients with soft tissue sarcoma of the extremities. Three escalating dose levels of TNFerade (4 × 109 −4 × 1011 particle units) were planned, given in 1 log increments by intratumoral injections, twice weekly during week 1 and once weekly during weeks 2–5 of radiation therapy. Results: TNFerade was well tolerated with no dose-limiting toxicities noted. Grade 1–2 chills (50.0%), fever (43.0%), fatigue (36.0%), and flu-like symptoms (21.0%) were the most common side effects. Serum-tumor necrosis factor α levels were low in all of the patients (&amp;lt;15 pg/mL). No patients had virus-detected blood, sputum, or urine cultures. Of the 13 evaluable patients, 11 received TNFerade preoperatively, and 2 received the treatment for palliation. Eleven patients (85%) showed objective or pathological tumor responses (2 complete and 9 partial), and 1 had stable disease. Partial responses were achieved despite some of these tumors being very large (up to 675 cm2). Of the 11 patients who underwent surgery, 10 (91%) showed a pathological complete response/partial response. Conclusion: TNFerade + radiation therapy was well tolerated in the treatment of patients with soft-tissue sarcoma of the extremity. The high number of objective responses observed warrants additional studies of this approach in a larger controlled prospective trial.
Non–Q-wave myocardial infarction following thrombolytic therapy: a comparison of outcomes in patients randomized to invasive or conservative post-infarct assessment strategies in the Veterans Affairs Non–Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial
Authors: Laura F. Wexler, Alvin S. Blaustein, Philip W. Lavori, Kenneth G. Lehmann, Michael Wade, William E. Boden
Journal: Journal of the American College of Cardiology (2001)
Analysis of rat hemopoietic cells on the fluorescence-activated cell sorter. II. Isolation of terminal deoxynucleotidyl transferase-positive cells.
Authors: I Goldschneider, D Metcalf, T Mandel, F J Bollum
Journal: The Journal of Experimental Medicine (1980)

A method is described by which highly enriched populations of viable terminal deoxynucleotidyl transferase-positive (TdT+) cells can be isolated from rat bone marrow by use of the fluorescence-activated cell sorter. Such cells have been postulated to be progenitors of thymocytes and, possibly, of B lymphocytes, and may serve as the targets of neoplastic transformation in acute lymphoblastic leukemia. The separation procedure is based on differences in relative low-angle light scatter and relative fluorescence intensity for Thy-1 antigen between TdT+ cells and other lymphohemopoietic cell populations in bone marrow. Simultaneous sorting of bone marrow cells according to these two parameters resulted in a mean 87% purification of TdT+ cells. The morphological characteristics of the isolated TdT+ cells are described at the light and electron miscroscopic levels.
Systemic treatment of advanced pancreatic cancer—step by step progress
Authors: Thomas Seufferlein
Journal: Gut (2012)

Advanced pancreatic cancer still has a dismal prognosis. For the past 15 years, gemcitabine has been the standard of care for this disease providing clinical benefit and a median overall survival of slightly more than 6 months. Many compounds have been examined in combination with gemcitabine, but only the addition of the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, led to a significant improvement in overall survival of the patients.1 However, the absolute improvement was only in the range of several days in the intention to treat population. A subgroup of patients, namely those who developed a skin rash in response to erlotinib, seemed to benefit more from the addition of the drug. Recently, a combination of 5-fluorouracil, oxaliplatin and irinotecan, the so-called FOLFIRINOX regimen, showed for the first time a marked improvement of overall survival (OS) in patients with metastatic pancreatic cancer compared with single-agent gemcitabine.2 This finding has two implications: Pancreatic cancer is not as chemotherapy-resistant as previously thought, and gemcitabine may not be the ideal combination partner for other chemotherapeutic agents in pancreatic cancer. How to proceed after failure of first-line chemotherapy in pancreatic cancer is still an open question.

Heinemann and colleagues3 investigated a sequential treatment with conventionally dosed gemcitabine, or capecitabine plus erlotinib, followed by the comparator cytostatic …
FGF21 Acts Centrally to Induce Sympathetic Nerve Activity, Energy Expenditure, and Weight Loss
Authors: Bryn M. Owen, Xunshan Ding, Donald A. Morgan, Katie Colbert Coate, Angie L. Bookout, Kamal Rahmouni, Steven A. Kliewer, David J. Mangelsdorf
Journal: Cell Metabolism (2014)
Innate Recognition of Bacteria in Human Milk Is Mediated by a Milk-Derived Highly Expressed Pattern Recognition Receptor, Soluble Cd14
Authors: Mario O. Labéta, Karine Vidal, Julia E. Rey Nores, Mauricio Arias, Natalio Vita, B. Paul Morgan, Jean Claude Guillemot, Denis Loyaux, Pascual Ferrara, Daniel Schmid, Michael Affolter, Leszek K. Borysiewicz, Anne Donnet-Hughes, Eduardo J. Schiffrin
Journal: The Journal of Experimental Medicine (2000)

Little is known about innate immunity to bacteria after birth in the hitherto sterile fetal intestine. Breast-feeding has long been associated with a lower incidence of gastrointestinal infections and inflammatory and allergic diseases. We found in human breast milk a 48-kD polypeptide, which we confirmed by mass spectrometry and sequencing to be a soluble form of the bacterial pattern recognition receptor CD14 (sCD14). Milk sCD14 (m-sCD14) concentrations were up to 20-fold higher than serum sCD14 from nonpregnant, pregnant, or lactating women. In contrast, lipopolysaccharide (LPS)-binding protein was at very low levels. Mammary epithelial cells produced 48-kD sCD14. m-sCD14 mediated activation by LPS and whole bacteria of CD14 negative cells, including intestinal epithelial cells, resulting in release of innate immune response molecules. m-sCD14 was undetectable in the infant formulas and commercial (cows') milk tested, although it was present in bovine colostrum. These findings indicate a sentinel role for sCD14 in human milk during bacterial colonization of the gut, and suggest that m-sCD14 may be involved in modulating local innate and adaptive immune responses, thus controlling homeostasis in the neonatal intestine.
Controlled Exposures to Air Pollutants and Risk of Cardiac Arrhythmia
Authors: Jeremy P. Langrish, Simon J. Watts, Amanda J. Hunter, Anoop S.V. Shah, Jenny A. Bosson, Jon Unosson, Stefan Barath, Magnus Lundbäck, Flemming R. Cassee, Ken Donaldson, Thomas Sandström, Anders Blomberg, David E. Newby, Nicholas L. Mills
Journal: Environmental Health Perspectives (2014)

Background: Epidemiological studies have reported associations between air pollution exposure and increases in cardiovascular morbidity and mortality. Exposure to air pollutants can influence cardiac autonomic tone and reduce heart rate variability, and may increase the risk of cardiac arrhythmias, particularly in susceptible patient groups.Objectives: We investigated the incidence of cardiac arrhythmias during and after controlled exposure to air pollutants in healthy volunteers and patients with coronary heart disease.Methods: We analyzed data from 13 double-blind randomized crossover studies including 282 participants (140 healthy volunteers and 142 patients with stable coronary heart disease) from whom continuous electrocardiograms were available. The incidence of cardiac arrhythmias was recorded for each exposure and study population.Results: There were no increases in any cardiac arrhythmia during or after exposure to dilute diesel exhaust, wood smoke, ozone, concentrated ambient particles, engineered carbon nanoparticles, or high ambient levels of air pollution in either healthy volunteers or patients with coronary heart disease.Conclusions: Acute controlled exposure to air pollutants did not increase the short-term risk of arrhythmia in participants. Research employing these techniques remains crucial in identifying the important pathophysiological pathways involved in the adverse effects of air pollution, and is vital to inform environmental and public health policy decisions.Citation: Langrish JP, Watts SJ, Hunter AJ, Shah AS, Bosson JA, Unosson J, Barath S, Lundbäck M, Cassee FR, Donaldson K, Sandström T, Blomberg A, Newby DE, Mills NL. 2014. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ Health Perspect 122:747–753; http://dx.doi.org/10.1289/ehp.1307337