tbuckley/cabot-search huggingface dataset:
Host Response to Short-term, Single-Agent Chemotherapy Induces Matrix Metalloproteinase-9 Expression and Accelerates Metastasis in Mice
Authors: Svetlana Gingis-Velitski, David Loven, Liat Benayoun, Michal Munster, Rotem Bril, Tali Voloshin, Dror Alishekevitz, Francesco Bertolini, Yuval Shaked
Journal: Cancer Research (2011)

Mounting evidence suggests that bone marrow-derived cells (BMDC) contribute to tumor growth, angiogenesis, and metastasis. In acute reactions to cancer therapy, several types of BMDCs are rapidly mobilized to home tumors. Although this host reaction to therapy can promote tumor regrowth, its contribution to metastasis has not been explored. To focus only on the effects of chemotherapy on the host, we studied non-tumor-bearing mice. Plasma from animals treated with the chemotherapy paclitaxel induced angiogenesis, migration, and invasion of tumor cells along with host cell colonization. Lesser effects were seen with the chemotherapy gemcitabine. Conditioned medium from BMDCs and plasma from chemotherapy-treated mice each promoted metastatic properties in tumor cells by inducing matrix metalloproteinase-9 (MMP9) and epithelial-to-mesenchymal transition. In mice in which Lewis lung carcinoma cells were injected intravenously, treatment with paclitaxel, but not gemcitabine or vehicle, accelerated metastases in a manner that could be blocked by an MMP9 inhibitor. Moreover, chimeric mice reconstituted with BMDC where MMP9 activity was attenuated did not support accelerated metastasis by carcinoma cells that were pretreated with chemotherapy before their introduction to host animals. Taken together, our findings illustrate how some chemotherapies can exert prometastatic effects that may confound treatment outcomes.
High inhaled corticosteroids adherence in childhood asthma: the role of medication beliefs
Authors: Ted Klok, Adrian A. Kaptein, Eric J. Duiverman, Paul L. Brand
Journal: European Respiratory Journal (2012)

Our aim was to study determinants of adherence in young asthmatic children over a 3-month period, including the role of parental illness and medication perceptions as determinants of adherence. Consecutive 2–6-yr-old children with asthma, using inhaled corticosteroids (ICS), followed-up at our paediatric asthma clinic (where patients are being extensively trained in self-management, and are followed-up closely) were enrolled. Adherence was measured electronically using a Smartinhaler® and calculated as a percentage of the prescribed dose. We examined the association of adherence to a range of putative determinants, including clinical characteristics and parental perceptions about illness and medication. Median (interquartile range) adherence, measured over 3 months in 93 children, was 92 (76–97)%, and most children had well controlled asthma. 94% of parents expressed the view that giving ICS to their child would protect him/her from becoming worse. Adherence was significantly associated with asthma control and with parental perceptions about medication. The high adherence rate observed in our study was associated with parental perceptions about ICS need. The high perceived need of ICS may probably be ascribed to the organisation of asthma care (with repeated tailored education and close follow-up).
Oral Uracil and Tegafur Plus Leucovorin Compared With Intravenous Fluorouracil and Leucovorin in Stage II and III Carcinoma of the Colon: Results From National Surgical Adjuvant Breast and Bowel Project Protocol C-06
Authors: Barry C. Lembersky, H. Samuel Wieand, Nicholas J. Petrelli, Michael J. O'Connell, Linda H. Colangelo, Roy E. Smith, Thomas E. Seay, Jeffrey K. Giguere, M. Ernest Marshall, Andrew D. Jacobs, Lauren K. Colman, Atilla Soran, Greg Yothers, Norman Wolmark
Journal: Journal of Clinical Oncology (2006)

The primary aim of this study was to compare the relative efficacy of oral uracil and tegafur (UFT) plus leucovorin (LV) with the efficacy of weekly intravenous fluorouracil (FU) plus LV in prolonging disease-free survival (DFS) and overall survival (OS) after primary surgery for colon carcinoma.Between February 1997 and March 1999, 1,608 patients with stage II and III carcinoma of the colon were randomly assigned to receive either oral UFT+LV or intravenous FU+LV.Of the total patients, 47% had stage II colon cancer, and 53% had stage III colon cancer. Median follow-up time was 62.3 months. The estimated hazard ratio (HR) for OS of patients who received UFT+LV versus that of patients who received FU+LV was 1.014 (95% CI, 0.825 to 1.246). The estimated HR for DFS was 1.004 (95% CI, 0.847 to 1.190). Cox proportional hazards model analyses with regard to age (< 60 v > or = 60 years), stage, or number of involved nodes (none v one to three v > or = four nodes) revealed no interaction with OS or DFS. Toxicity was similar in the two groups. In the UFT+LV arm, 38.2% of patients experienced any grade 3 or 4 toxic event compared with 37.8% of patients in the FU+LV arm. Primary quality-of-life end points did not differ between the two regimens, although convenience of care analysis favored UFT+LV.UFT+LV achieved similar DFS and OS when compared with an intravenous, weekly, bolus FU+LV regimen. The two regimens were equitoxic and generally well tolerated.
Serum Levels of an Isoform of Apolipoprotein A-II as a Potential Marker for Prostate Cancer
Authors: Gunjan Malik, Michael D. Ward, Saurabh K. Gupta, Michael W. Trosset, William E. Grizzle, Bao-Ling Adam, Jose I. Diaz, O. John Semmes
Journal: Clinical Cancer Research (2005)

We recently showed that protein expression profiling of serum using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) has potential as a diagnostic approach for detection of prostate cancer. As a parallel effort, we have been pursuing the identification of the protein(s) comprising the individual discriminatory "peaks" and evaluating their utility as potential biomarkers for prostate disease.We employed liquid chromatography, gel electrophoresis and tandem mass spectroscopy to isolate and identify a protein that correlates with observed SELDI-TOF MS mass/charge (m/z) values. Immunodepletion, immunoassay, and Western analysis were used to verify that the identified protein generated the observed SELDI peak. Subsequent immunohistochemistry was used to examine the expression of the proteins in prostate tumors.An 8,946 m/z SELDI-TOF MS peak was found to retain discriminatory value in each of two separate data sets with an increased expression in the diseased state. Sequence identification by liquid chromatography-MS/MS and subsequent immunoassays verified that an isoform of apolipoprotein A-II (ApoA-II) is the observed 8,946 m/z SELDI peak. Immunohistochemistry revealed that ApoA-II is overexpressed in prostate tumors. SELDI-based immunoassay revealed that an 8.9-kDa isoform of ApoA-II is specifically overexpressed in serum from individuals with prostate cancer. ApoA-II was also overexpressed in the serum of individuals with prostate cancer who have normal prostate-specific antigen (0-4.0 ng/mL).We have identified an isoform of ApoA-II giving rise to an 8.9K m/z SELDI "peak" that is specifically overexpressed in prostate disease. The ability of ApoA-II to detect disease in patients with normal prostate-specific antigen suggests potential utility of the marker in identifying indolent disease.
Biotechnology: Delivering on the Promise
Authors: James C. Greenwood
Journal: Science Translational Medicine (2010)

The research and development of innovative new therapies are expensive and risky processes, and companies require substantial resources if they are to translate basic science into modern biomedical products. When resources are limited, as in the current economic climate, biotechnology start-up companies are often among the first casualties in the fight for assets. Policy-makers can play an important role in bolstering these important innovators.
Functional and immunocytochemical evidence for a role of ghrelin and des-octanoyl ghrelin in the regulation of vascular tone in man
Authors: M KLEINZ, J MAGUIRE, J SKEPPER, A DAVENPORT
Journal: Cardiovascular Research (2005)

Objective: Ghrelin is the recently identified endogenous ligand for the ghrelin receptor GHS-R1a and known to regulate growth hormone secretion and appetite. Ghrelin also is a potent vasodilator and improves cardiac performance after systemic administration. Generally, the octanoyl modification on Ser3 has been considered essential for biological activity. Recently however, cardiovascular actions of des-octanoyl ghrelin have been reported in rodents. Our aim was to investigate if ghrelin and ghrelin receptor protein are expressed within the human vasculature, to determine if des-octanoyl ghrelin, like ghrelin, is a vasodilator in human artery and to test the acute effect of ghrelin peptides on cardiac contractility.
Sustained Activation of Lyn Tyrosine Kinase In Vivo Leads to Autoimmunity
Authors: Margaret L. Hibbs, Kenneth W. Harder, Jane Armes, Nicole Kountouri, Cathy Quilici, Franca Casagranda, Ashley R. Dunn, David M. Tarlinton
Journal: The Journal of Experimental Medicine (2002)

Genetic ablation of the Lyn tyrosine kinase has revealed unique inhibitory roles in B lymphocyte signaling. We now report the consequences of sustained activation of Lyn in vivo using a targeted gain-of-function mutation (Lynup/up mice). Lynup/up mice have reduced numbers of conventional B lymphocytes, down-regulated surface immunoglobulin M and costimulatory molecules, and elevated numbers of B1a B cells. Lynup/up B cells are characterized by the constitutive phosphorylation of negative regulators of B cell antigen receptor (BCR) signaling including CD22, SHP-1, and SHIP-1, and display attributes of lymphocytes rendered tolerant by constitutive engagement of the antigen receptor. However, exaggerated positive signaling is also apparent as evidenced by the constitutive phosphorylation of Syk and phospholipase Cγ2 in resting Lynup/up B cells. Similarly, Lynup/up B cells show a heightened calcium flux in response to BCR stimulation. Surprisingly, Lynup/up mice develop circulating autoreactive antibodies and lethal autoimmune glomerulonephritis, suggesting that enhanced positive signaling eventually overrides constitutive negative signaling. These studies highlight the difficulty in maintaining tolerance in the face of chronic stimulation and emphasize the pivotal role of Lyn in B cell signaling.
Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome
Authors: Nathaniel D Heintzman, Rhona K Stuart, Gary Hon, Yutao Fu, Christina W Ching, R David Hawkins, Leah O Barrera, Sara Van Calcar, Chunxu Qu, Keith A Ching, Wei Wang, Zhiping Weng, Roland D Green, Gregory E Crawford, Bing Ren
Journal: Nature Genetics (2007)
Serum leptin and adiponectin are positively associated with bone mineral density at the distal radius in patients with type 2 diabetes mellitus
Authors: Tomoko Tamura, Masayasu Yoneda, Kiminori Yamane, Shuhei Nakanishi, Reiko Nakashima, Masamichi Okubo, Nobuoki Kohno
Journal: Metabolism (2007)
Mutations in ZBTB20 cause Primrose syndrome
Authors: Viviana Cordeddu, Bert Redeker, Emilia Stellacci, Aldo Jongejan, Alessandra Fragale, Ted E J Bradley, Massimiliano Anselmi, Andrea Ciolfi, Serena Cecchetti, Valentina Muto, Laura Bernardini, Meron Azage, Daniel R Carvalho, Alberto J Espay, Alison Male, Anna-Maja Molin, Renata Posmyk, Carla Battisti, Alberto Casertano, Daniela Melis, Antoine van Kampen, Frank Baas, Marcel M Mannens, Gianfranco Bocchinfuso, Lorenzo Stella, Marco Tartaglia, Raoul C Hennekam
Journal: Nature Genetics (2014)
Improving Health Care for Older Persons
Authors: C Seth Landefeld
Journal: Annals of Internal Medicine (2003)

Health care of the highest quality promotes successful aging. This paper examines the efforts that have been taken to improve the quality of health care, especially hospital care. Most of these efforts have evaluated conventional treatments of specific diseases; they are critical but underfunded and underused, and many practices persist without much evidence of efficacy. Fewer efforts have attempted to improve care for groups of persons in specific settings, such as the hospital. Three complementary approaches to improving comprehensive outcomes for hospitalized older personsGeriatric Evaluation and Management, Acute Care for Elders, and the Elder Life Programdemonstrate what has been learned about improving care for older persons by redesigning microsystems of care. A research agenda for advancing successful aging should include specific actions to improve the quality of health care.
Immediate Listing for Liver Transplantation Versus Standard Care for Child–Pugh Stage B Alcoholic Cirrhosis
Authors: Claire Vanlemmens, Vincent Di Martino, Chantal Milan, Michel Messner, Anne Minello, Christophe Duvoux, Thierry Poynard, Jean-Marc Perarnau, Marie-Anne Astrid Piquet, Georges-Philippe Pageaux, Sébastien Dharancy, Christine Silvain, Sophie Hillaire, Gérard Thiefin, Jean-Pierre Vinel, Patrick Hillon, Estelle Collin, Georges Mantion, Jean-Philippe Miguet, Non Renseigné
Journal: Annals of Internal Medicine (2009)

Background: Liver transplantation improves survival of patients with end-stage (Child–Pugh stage C) alcoholic cirrhosis, but its benefit for patients with stage B disease is uncertain. Objective: To compare the outcomes of patients with Child–Pugh stage B alcoholic cirrhosis who are immediately listed for liver transplantation with those of patients assigned to standard treatment with delay of transplantation until progression to stage C disease. Design: Randomized, controlled trial. Setting: 13 liver transplantation programs in France. Patients: 120 patients with Child–Pugh stage B alcoholic cirrhosis and no viral hepatitis, cancer, or contraindication to transplantation. Interventions: Patients were randomly assigned to immediate listing for liver transplantation (60 patients) or standard care (60 patients). Measurements: Overall and cancer-free survival over 5 years. Results: Sixty-eight percent of patients assigned to immediate listing for liver transplantation and 25% of those assigned to standard care received a liver transplant. All-cause death and cirrhosis-related death did not statistically differ between the 2 groups: 5-year survival was 58% (95% CI, 43% to 70%) for those assigned to immediate listing versus 69% (CI, 54% to 80%) for those assigned to standard care. In multivariate analysis, independent predictors of long-term survival were absence of ongoing alcohol consumption (hazard ratio, 7.604 [CI, 2.395 to 24.154]), recovery from Child–Pugh stage C (hazard ratio, 7.633 [CI, 2.392 to 24.390]), and baseline Child–Pugh score less than 8 (hazard ratio, 2.664 [CI, 1.052 to 6.746]). Immediate listing for transplantation was associated with an increased risk for extrahepatic cancer: The 5-year cancer-free survival rate was 63% (CI, 43% to 77%) for patients who were immediately listed and 94% (CI, 81% to 98%) for those who received standard care. Limitation: Restriction of the study sample to alcoholic patients may limit the generalizability of results to other settings. Conclusion: Immediate listing for liver transplantation did not show a survival benefit compared with standard care for Child–Pugh stage B alcoholic cirrhosis. In addition, immediate listing for transplantation increased the risk for extrahepatic cancer. Funding: The French National Program for Clinical Research.
Inflammation and Repair Processes in Chronic Obstructive Pulmonary Disease
Authors: STEPHEN I. RENNARD
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

AM J RESPIR CRIT CARE MED 1999;160:S12−S16.COPD is characterized by chronic inflammation and injury of both the airways and the parenchymal structures of the lung. These processes are associated with ongoing repair. Whether repair leads to restoration of normal tissue architecture or to altered tissue structure with loss of function depends on complex interrelationships of a variety of interacting mediators. The possibility that repair processes can be modulated by exogenous agents raises the possibility that therapeutic strategies aimed at repair can be effective. Such strategies offer tremendous promise both for slowing the relentlessly progressive natural history which most often characterizes COPD and, possibly, for restoring lung function. Rennard SI. Inflammation and repair processes in chronic obstructive pulmonary disease.
Off-hour presentation and outcomes in patients with acute myocardial infarction: systematic review and meta-analysis
Authors: A. Sorita, A. Ahmed, S. R. Starr, K. M. Thompson, D. A. Reed, L. Prokop, N. D. Shah, M. H. Murad, H. H. Ting
Journal: BMJ (2014)

To assess the association between off-hour (weekends and nights) presentation, door to balloon times, and mortality in patients with acute myocardial infarction.Medline in-process and other non-indexed citations, Medline, Embase, Cochrane Database of Systematic Reviews, and Scopus through April 2013.Any study that evaluated the association between time of presentation to a healthcare facility and mortality or door to balloon times among patients with acute myocardial infarction was included.Studies' characteristics and outcomes data were extracted. Quality of studies was assessed with the Newcastle-Ottawa scale. A random effect meta-analysis model was applied. Heterogeneity was assessed using the Q statistic and I(2).48 studies with fair quality, enrolling 1,896,859 patients, were included in the meta-analysis. 36 studies reported mortality outcomes for 1,892,424 patients with acute myocardial infarction, and 30 studies reported door to balloon times for 70,534 patients with ST elevation myocardial infarction (STEMI). Off-hour presentation for patients with acute myocardial infarction was associated with higher short term mortality (odds ratio 1.06, 95% confidence interval 1.04 to 1.09). Patients with STEMI presenting during off-hours were less likely to receive percutaneous coronary intervention within 90 minutes (odds ratio 0.40, 0.35 to 0.45) and had longer door to balloon time by 14.8 (95% confidence interval 10.7 to 19.0) minutes. A diagnosis of STEMI and countries outside North America were associated with larger increase in mortality during off-hours. Differences in mortality between off-hours and regular hours have increased in recent years. Analyses were associated with statistical heterogeneity.This systematic review suggests that patients with acute myocardial infarction presenting during off-hours have higher mortality, and patients with STEMI have longer door to balloon times. Clinical performance measures may need to account for differences arising from time of presentation to a healthcare facility.
Israel to move more psychiatric services into the community
Authors: J. Siegel-Itzkovich
Journal: BMJ (2003)

After a seven year delay the government of Israel has decided to shift responsibility for mental health care from the health ministry to the four public health funds that insure the entire population.

All involved—the insurers, the health ministry, patients' groups, staff at psychiatric hospitals and clinics, and the finance ministry—have finally endorsed the change, which will become effective on 15 April. Inpatient and outpatient psychiatric care will be included in the basket of health services supplied by the health funds to all Israelis who need it.

The reform is also intended to reduce the stigma …
Cardiac Malformations in Rats Induced by Exposure of the Mother to Carbon Dioxide During Pregnancy
Authors: OLGA M. HARING
Journal: Circulation Research (1960)

Seventy-one pregnant rats of a Sprague-Dawley strain were exposed for a single 24-hour period to a gas mixture of 6 per cent carbon dioxide, 20 per cent oxygen and 74 per cent nitrogen on different days during gestation. There were 530 offspring and these were compared with 159 newborn rats from 21 control dams. The incidence of cardiac malformations was 23.4 per cent in the test group and 6.8 per cent in the control group with the highest incidence in the test group occurring when the exposure was on the tenth day of gestation. Isolated ventricular septal defects, situated in the lower and posterior part of the muscle septum, were found in 8 cases, ventricular septal defects with overriding aorta in 24 cases and ventricular septal defects with partial transposition in 20 cases. Forty-seven of the abnormal hearts had a myocardial thickening accompanied by narrowing of the pulmonic or aortic outflow channel with or without other abnormalities, such as atresia of the mitral or tricuspid valves and hypoplasia of the aorta or pulmonary artery. There was a slight increase in perinatal mortality in the test group, and a lower frequency of male offspring. The average body weight was 18.9 per cent higher in the test group.
Small tumor of the medial breast presenting with a contralateral lymph node involvement detected on positron emission tomography scan
Authors: G. Facchini, M. Caraglia, G. Nasti, A. Ottaiano, R. Franco, A. La Mura, F. Fulciniti, M. Libutti, M. Ruberto, M. Marra, A. Budillon, R.V. Iaffaioli
Journal: Annals of Oncology (2007)
Current standards for the storage of human samples in biobanks
Authors: Tim Peakman, Paul Elliott
Journal: Genome Medicine (2010)

Biobanks are diverse in their design and purpose; the idea of fully harmonizing historical and future biobanks is unaffordable and unfeasible. Biobanks should focus their efforts instead on developing and maintaining high-quality collections of samples capable of providing a wide range of biological information using processes that minimize introduced variability. A full data audit trail on sample processing, archiving, and quality control procedures should also be provided. This should enable the data derived from biobanks to contribute as part of wider collaborative efforts with other similar resources.
On the Mechanism of Polyuria in Potassium Depletion
Authors: Tomas Berl, Stuart L. Linas, Gary A. Aisenbrey, Robert J. Anderson
Journal: Journal of Clinical Investigation (1977)

The association of potassium (K) depletion with polyuria and a concentrating defect is established, but the extent to which these defects could be secondary to an effect of low K on water intake has not been systematically investigated. To determine whether hypokalemia has a primary effect to increase thirst and whether any resultant polyuria and polydipsia contribute to the concentrating defect, we studied three groups of rats kept in metabolic cages for 15 days. The groups were set up as follows: group 1, normal diets and ad lib. fluids (n = 12); group 2, K-deficient diet on ad lib. fluids (n = 12); and group 3, K-deficient diet and fluid intake matched to group 1 (n = 14). Daily urine flow and urinary osmolality of groups 1 and 3 were not significantly different throughout the study. In contrast, as of day 6, group 2 rats consistently had a higher fluid intake (P < 0.0025), higher urine flow (P < 0.001), and lower urinary osmolality (P < 0.001) than the other two groups. These alterations in fluid intake and urine flow preceded a defect in maximal concentrating ability. On day 7, maximal urinary osmolality was 2,599±138 msmol/kg in rats on K-deficient intake and 2,567±142 msmol/kg in controls. To determine whether this primary polydipsia is itself responsible for the development of the concentrating defect, the three groups of rats were dehydrated on day 15. Despite different levels of fluid intake, maximal urinary osmolality was impaired equally in groups 2 and 3 (1,703 and 1,511 msmol/kg, respectively), as compared to rats in group 1 (2,414 msmol/kg), P < 0.001. We therefore conclude that K depletion stimulates thirst, and the resultant increase in water intake is largely responsible for the observed polyuria. After 15 days of a K-deficient diet, the impaired maximal urinary concentration in hypokalemia, however, was not related to increased water intake, since fluid restriction did not abolish the renal concentrating defect.