tbuckley/cabot-search huggingface dataset:
Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells.
Authors: N F Go, B E Castle, R Barrett, R Kastelein, W Dang, T R Mosmann, K W Moore, M Howard
Journal: The Journal of Experimental Medicine (1990)

Highly purified, small dense splenic B cells from unstimulated mice showed increased expression of class II major histocompatibility complex (MHC) antigens and enhanced viability when cultured with affinity-purified recombinant interleukin 10 (rIL-10), compared with B cells cultured in medium alone. These responses were blocked by a monoclonal antibody (mAb) specific for IL-10, but not by an isotype-matched control antibody. IL-10 did not upregulate the expression of Fc epsilon receptors (CD23) or class I MHC antigens on small dense B cells or induce their replication as monitored by [3H]thymidine incorporation. While these B cell-stimulatory properties of IL-10 are also mediated by IL-4, the two cytokines appear to act independently in these assays; anti-IL-10 antibodies blocked IL-10 but not IL-4-mediated B cell viability enhancement, and vice versa. Similarly, since IL-4 upregulates CD23 on small dense B cells, the inability of IL-10 to do so argues against its acting via endogenously generated IL-4. Finally, IL-10 did not upregulate class II MHC antigens on B cells from X chromosome-linked immunodeficiency (XID) mice, while the same cells showed normal upregulation of class II antigens in response to IL-4. This report also extends our understanding of the relationship between IL-10 and the highly homologous Epstein-Barr virus (EBV)-encoded Bam HI fragment C rightward reading frame no. 1 (BCRFI) protein. It has previously been shown that BCRFI protein exhibits the cytokine synthesis inhibitory activity of IL-10. This report indicates that BCRFI protein also enhances in vitro B cell viability, but does not upregulate class II MHC antigens on B cells. One explanation for these data is that IL-10 contains at least two functional epitopes, only one of which has been conserved by EBV.
INTERLEUKIN 23 REDUCES MYOCARDIAL INFLAMMATION AND IMPROVES INFARCT HEALING AFTER EXPERIMENTAL MYOCARDIAL INFARCTION BY CONTROLING THE FUNCTION OF CARDIAC FIBROBLASTS
Authors: Konstantinos Savvatis, Kathleen Pappritz, Dirk Westermann, Peter-Moritz Becher, Heinz-Peter Schultheiss, Carsten Tschöpe
Journal: Journal of the American College of Cardiology (2013)
Fish oil protects mice against acetaminophen hepatotoxicityin vivo
Authors: Robert F. Speck, Bernhard H. Lauterburg
Journal: Hepatology (1991)

Recent observations suggest that products of nonparenchymal liver cells such as eicosanoids and cytokines might play a role in the expression of liver injury after administration of acetaminophen and other noxious agents. We therefore investigated the effect of a fish oil diet, which results in the generation of eicosanoids with altered biological properties and suppresses the production of certain cytokines on acetaminophen hepatotoxicity. Mice were fed a diet with either 20% fish oil containing n-3 fatty acids or 20% olive oil containing n-6 fatty acids for 2 wk. Cytochrome P-450 activity and the concentration of glutathione were similar in the two groups before acetaminophen administration. Nevertheless, 24 hr after the administration of 375 mg/kg acetaminophen intraperitoneally, the extent of centrilobular necrosis and the activity of ALT in plasma were significantly lower in the n-3 fatty acid group (median = 277 vs. 3,367 IU/L; p < 0.001). In the n-3 fatty acid group covalent binding of the drug to liver proteins (0.19 ± 0.03 vs. 0.67 ± 0.07 nmol/mg protein; p < 0.01) and the median plasma concentration of acetaminophen (0.1 vs. 0.6 mmol/L) were significantly lower 3 hr after dosing. Mice fed the n-3 fatty acid diet excreted less acetaminophen sulfate but significantly more acetaminophen glucuronide in 24 hr. Thus the major protective effect of the fish oil diet appears to be an increased clearance of acetaminophen resulting from a stimulation of the glucuronidation of acetaminophen, which may be due to the fluidization of microsomal membranes by fish oil. (HEPATOLOGY 1991;13:557–561.)
Disposition of Xenobiotic Chemicals and Metabolites in Marine Organisms
Authors: Usha Varanasi, John E. Stein
Journal: Environmental Health Perspectives (1991)

Studies with several bottom fish species from urban waterways show that ofthe identified xenobiotic chemicals in bot- tom sediments, polycylic aromatic hydrocarbons (PAHs) are the most strongly associated with the prevalence of liver le- sions, includ neoplasms.Accordingly, there is concern about the transfer ofcontaminants, such as PAHs, from aquatic s s to hum Because PAlHseerttheirtaidty only after being lorm ed, incing attention has been focused on the ability ofaquatic organiss to metabolize these chemicals.Overall, the reslts of both laboratory and field studies show that generafly low levels (nanograms per gram wet weight) of a few low molecular weight PAHs may be present in edible tissue offish from areas and that high nmoeuar weiglt PAHs, such as the carcnogen benzo(a)pyrene, wil rrely be debtcted because ofexensivenueAbolin. Addiionally, the rets from a few studies suggest that even though interactions between xenobiotics can affect both biochemical and physiological systems to alter the disposition of PAHs in fish, these interctons do not markdly change the relative proportions of metabolites to parent PAH in tissues.Thus, these studies clearly demonstrate that to obtain some insight into the questonsofwheter there is any risk to human health from consuming fish and crustaeans from urban areas, techniques must be developed that measure metabolites ofcar- cinogens, such as PAHs, in edible tissue.Initial attempts may focuson semiquantitative mthodsthat permit rapid assess- ment of the levd of metabolites in edible tissues of fish and crustaceans from many urban areas.Based on information from such screening studies, further refinement in methodology leading to identification ofspecific compounds may be needed becausecertain metaboltes may not be as toc or carcngenik as othem A scientifiall sound database on a broad spectrum ofcontaminants and their metabolites in aquatic species is needed before we can adequately address the ques- tion of bioavailability or food chain transfer of these compounds to humans.
Hemodynamic Profile After the Norwood Procedure With Right Ventricle to Pulmonary Artery Conduit
Authors: Kevin O. Maher, Christian Pizarro, Samuel S. Gidding, Katarzyna Januszewska, Edward Malec, William I. Norwood, John D. Murphy
Journal: Circulation (2003)

The balance of systemic, pulmonary, and coronary blood flow after the Norwood operation for hypoplastic left heart syndrome (HLHS) is critical to early survival. We hypothesized that a right ventricle to pulmonary artery conduit (instead of a systemic to pulmonary artery shunt) would result in hemodynamic changes consistent with a more stable balance of systemic, pulmonary, and coronary perfusion.Hemodynamic data were obtained during cardiac catheterization before the hemi-Fontan procedure from 24 patients with HLHS; the first 10 had a Norwood operation with a systemic to pulmonary artery shunt, and the latter 14 had the Norwood operation with a right ventricle to pulmonary artery conduit. Significant differences were present, with the right ventricle to pulmonary artery conduit group having a higher aortic diastolic pressure (55 versus 42 mm Hg), a narrowed systemic pulse pressure (43 versus 64 mm Hg), a lower Qp:Qs (0.92 versus 1.42), a higher coronary perfusion pressure (46 versus 32 mm Hg), and a higher ratio of pulmonary artery diameter to descending aorta diameter (1.51 versus 1.37).We conclude that, in HLHS after the Norwood operation, the right ventricle to pulmonary artery conduit modification produces hemodynamic changes consistent with improved coronary perfusion and a more favorable distribution of systemic, pulmonary, and coronary blood flow.
Taxol: A Unique Antineoplastic Agent with Significant Activity in Advanced Ovarian Epithelial Neoplasms
Authors: William P. McGuire
Journal: Annals of Internal Medicine (1989)

Study Objective: To assess the activity of taxol in patients with advanced, progressive, and drug-refractory ovarian cancer and to delineate more clearly the toxicity of taxol in this patient population. Design: Nonrandomized, prospective phase II trial. Patients: Forty-seven patients with drug-refractory epithelial ovarian cancer who had one or more lesions measurable in perpendicular diameters. Of these patients, 45 were evaluable for toxicity and 40 were evaluable for response. Interventions: Patients were treated every 22 days with varying doses of taxol (110 to 250 mg/m2 body surface) given as a 24-hour infusion with subsequent doses based on adverse effects. A premedication regimen was used to avoid acute hypersensitivity reactions. Measurements and Main Results: Twelve patients (30%; CI, 16% to 44%) responded to taxol for periods lasting from 3 to 15 months. The dose-limiting toxicity was myelosuppression with leukocytes affected more severely and commonly than thrombocytes or reticulocytes. Leukopenia was usually brief in duration but was associated with sepsis in 3 cases (2 fatal). Other adverse effects included myalgias, arthralgias, alopecia, diarrhea, nausea, vomiting, mucositis, and peripheral neuropathy. Rare cases of cardiac and central neurotoxicity were also noted. Conclusions: Taxol is an active agent in drug-refractory ovarian cancer and deserves further study in combination with other active drugs in previously untreated patients with advanced ovarian cancer.
CYTOCHROME P450 2C19*17 POLYMORPHISM OFFSETS THE NEGATIVE EFFECT OF 2C19*2 POLYMORPHISM ON PLATELET REACTIVITY IN PATIENTS TREATED WITH CLOPIDOGREL
Authors: Jean-Pierre Dery, Erick Tourigny, Ugo Déry, Helena Tizon-Marcos, Rodrigo Bagur, Josep Rodés-Cabau, Eric Larose, Stephane Rinfret, Onil Gleeton, Guy Proulx, Gérald Barbeau, Bernard Noël, Louis Roy, Robert De Larochellière, Can Manh Nguyen, Yohan Bossé, Pierluigi Tricoci, Richard C. Becker
Journal: Journal of the American College of Cardiology (2011)
Phase II Evaluation of Carboplatin in Advanced Endometrial Carcinoma1
Authors: H. J. Long, D. M. Pfeifle, H. S. Wieand, J. E. Krook, J. H. Edmonson, J. C. Buckner
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Phase II Evaluation of Carboplatin in Advanced Endometrial Carcinoma1 Get access H. J. Long, H. J. Long 3Division of Medical Oncology (H. J. Long, J. H. Edmonson, J. C. Buckner) and Cancer Center Statistics Unit (H. S. Wieand), Maya ClinicRochester, MN. Search for other works by this author on: Oxford Academic PubMed Google Scholar D. M. Pfeifle, D. M. Pfeifle 4Quain and Ramstad ClinicBismarck, ND. Search for other works by this author on: Oxford Academic PubMed Google Scholar H. S. Wieand, H. S. Wieand 3Division of Medical Oncology (H. J. Long, J. H. Edmonson, J. C. Buckner) and Cancer Center Statistics Unit (H. S. Wieand), Maya ClinicRochester, MN. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. E. Krook, J. E. Krook 5Duluth Clinic CCOPDuluth, MN. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. H. Edmonson, J. H. Edmonson 3Division of Medical Oncology (H. J. Long, J. H. Edmonson, J. C. Buckner) and Cancer Center Statistics Unit (H. S. Wieand), Maya ClinicRochester, MN. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. C. Buckner J. C. Buckner * 3Division of Medical Oncology (H. J. Long, J. H. Edmonson, J. C. Buckner) and Cancer Center Statistics Unit (H. S. Wieand), Maya ClinicRochester, MN. *Correspondence to: North Central Cancer Treatment Group, Operations Office, 200 First St. S.W., Rochester, MN 55905. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 4, 20 April 1988, Pages 276–278, https://doi.org/10.1093/jnci/80.4.276 Published: 20 April 1988 Article history Received: 21 December 1987 Revision received: 22 February 1988 Accepted: 23 February 1988 Published: 20 April 1988
A Randomized Trial of Maintenance Therapy for Vasculitis Associated with Antineutrophil Cytoplasmic Autoantibodies
Authors: David Jayne, Niels Rasmussen, Konrad Andrassy, Paul Bacon, Jan Willem Cohen Tervaert, Jolanta Dadoniené, Agneta Ekstrand, Gill Gaskin, Gina Gregorini, Kirsten de Groot, Wolfgang Gross, E. Christiaan Hagen, Eduardo Mirapeix, Erna Pettersson, Carl Siegert, Alberto Sinico, Vladimir Tesar, Kerstin Westman, Charles Pusey
Journal: New England Journal of Medicine (2003)

The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission.
Three journals raise doubts on validity of Canadian studies
Authors: C. White
Journal: BMJ (2004)

Suspicions about the validity of research by Professor Ranjit Kumar Chandra, a prominent Canadian researcher, have been raised by three journals, including the BMJ .

The latest concern, in an editorial and a letter in the November issue of Nutrition (2003;19: 955-6 and 976-80) question research published in that journal by Professor Chandra in September 2001 (17:709-12).

The Nutrition study was a randomised, blind, placebo controlled trial. It showed that a specific multivitamin and mineral supplement could improve cognitive function in people aged over 65 years. Professor Chandra, who was the sole author, concluded that the supplement might delay the onset of Alzheimer's disease.

The original paper and the most recent letter and editorial questioning its validity have attracted considerable media attention.

> The BMJ's statistical reviewer concluded that the data had “all the hallmarks of being entirely invented.” 

The 2001 paper in Nutrition is almost identical to a paper submitted to the BMJ in October 2000, which followed up a trial published in the Lancet in 1992 (340: 1124-7)

The BMJ paper was not published because of serious problems identified during peer review. These problems included the lengthy period between the Lancet trial and submission of the manuscript on the same set of data to the BMJ and doubts that a major trial could have been undertaken by one man, who, …
1263 Evaluation of ablated area of percutaneous radiofrequency ablation, using leveen needle electrode, of small hepatocellular carcinoma with CT imaging
Authors: S KIRA, S DATE, Y YAMASHITA, T KAWAKAMI, K SUMII, Y SUMIDA
Journal: Hepatology (2003)

Hepatocellular carcinoma (HCC) is one of the most deadly human cancers. Chronic hepatitis B virus (HBV) infection is one of the predominant risk factors associated with the development of HCC and complicates the treatment of HCC. In this study, we demonstrate that a HBV-positive HCC cell line HepG2.2.15, was more resistant to chemotherapy agents than its parental HBV-negative cell line HepG2. HBV-positive HCC cells exhibited defective Chk1 phosphorylation and increased chromosomal instability. CGK733, a small molecule inhibitor reportedly targeting the kinase activities of ATM and ATR, significantly enhanced taxol-induced cytotoxicity in HBV-positive HepG2.2.15 cells. The mechanism lies in CGK733 triggers the formation of multinucleated cells thus promotes the premature mitotic exit of taxol-induced mitotic-damaged cells through multinucleation and mitotic catastrophe in HBV-positive HepG2.2.15 cells. These results suggest that CGK733 could potentially reverse the taxol resistance in HBV-positive HCC cells and may suggest a novel strategy to treat HBV-infected HCC patients.
Granulocytes in Human Disease
Authors: MARTIN J. CLINE
Journal: Annals of Internal Medicine (1974)

The neutrophilic granulocyte develops from a committed hemopoietic stem cell under hormonal and microenvironmental influences. By the promyelocyte stage it begins to develop its arsenal of lysosomal enzymes and soon thereafter develops its phagocytic capabilities. These two features—phagocytosis and lysosomal enzymes—are critical in supporting the neutrophil's defense function and play a key role in many inflammatory reactions. Abnormalities of granulocyte production, morphogenesis, or function occur in a wide variety of human disorders. The discussions that follow review the physiology and function of the normal cell and the aberrations that occur in granulocytic diseases.
Emerging Applications of Argatroban in the Management of Systemic Malignancies
Authors: Shailendra Kapoor
Journal: Circulation Research (2013)

The recent article by Coppens et al 1 provided for highly stimulating reading.Argatroban may exert several antineoplastic effects besides its antithrombin effects.Argatroban exerts significant antineoplastic effects in gliomas. 2 Thrombin, in general, augments the growth and progression of gliomas. 3Thrombin mediates its neoplastic role by increasing DNA synthesis within the cancer cells.It also accentuates intratumoral production of vascular endothelial growth factor.Thrombininduced vascular endothelial growth factor production by the neurons is markedly mitigated by argatroban. 4 Administration of argatroban blocks and reverses these neoplastic effects of thrombin.Neurological deficits secondary to gliomas are decreased, 5 and concurrent brain edema is also decreased.Simultaneously, the survival time is increased markedly.Argatroban also attenuates bone metastasis from breast carcinomas.It mediates its antineoplastic role by inhibiting thrombin-induced secretion of vascular endothelial growth factor. 6These effects have been seen both in vivo and in vitro.Argatroban also inhibits osteopontin-dependent cancer cell migration in breast cancers. 7dhesion is also markedly altered.As a result, lymphatic metastases in mammary malignancies are markedly decreased.Similarly, argatroban attenuates metastasis in melanomas. 8These effects are dose-dependent.Interestingly, argatroban also attenuates ischemia/ reperfusion-induced liver metastasis from colon carcinomas.It mediates this effect by accentuating prostaglandin 12 production.As a result TNF-α-induced expression of E-selectin is markedly decreased. 9he above examples clearly illustrate that argatroban has a significant role to play in the management of various systemic tumors and that further research is needed in this regard.
Radioembolization with yttrium-90 glass microspheres in hepatocellular carcinoma: European experience on safety and long-term survival
Authors: Philip Hilgard, Monia Hamami, Amr El Fouly, André Scherag, Stefan Müller, Judith Ertle, Till Heusner, Vito R. Cicinnati, Andreas Paul, Andreas Bockisch, Guido Gerken, Gerald Antoch
Journal: Hepatology (2010)

Radioembolization has been demonstrated to allow locoregional therapy of patients with hepatocellular carcinoma not eligible for transarterial chemoembolization or other local therapies. The aim of this study was to validate evidence of the safety and efficacy of this treatment in a European sample of patients with advanced hepatocellular carcinoma (HCC). Therefore, 108 consecutive patients with advanced HCC and liver cirrhosis were included. Yttrium-90 (Y-90) microspheres were administered in a lobar fashion over the right or left branch of the hepatic artery. The response to treatment was evaluated by computed tomography (CT) imaging applying Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria with recent European Association for the Study of the Liver / National Cancer Institute (EASL/NCI) amendments. Time to progression (TTP) and overall survival were estimated by the Kaplan-Meier method. In all, 159 treatment sessions were performed ranging between one to three treatments per patient. The mean radiation dose per treatment was 120 (±18) Gy. According to EASL criteria, complete responses were determined in 3% of patients, partial responses in 37%, stable disease 53%, and primary progression in 6% of patients. TTP was 10.0 months, whereas the median overall survival was 16.4 months. No lung or visceral toxicity was observed. The most frequently observed adverse events was a transient fatigue-syndrome. Conclusion: Radioembolization with Y-90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function. Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC, randomized controlled trials in combination with systemic therapy are warranted. (Hepatology 2010;52:1741-1749)
The Uncertain Future of Managed Care
Authors: E Ginzberg
Journal: New England Journal of Medicine (1999)

The fortunes of managed care have taken a sudden downturn. Consider this: the oldest and largest and one of the most respected health maintenance organizations (HMOs), Kaiser Permanente, posted a loss of about $270 million in 1997, its first deficit in more than a half-century of operations. Informed sources predict even higher losses for 1998.Oxford Health Plans, a Connecticut-based, for-profit managed-care company with many middle- and upper-income enrollees in the New York region, saw its stock-market price peak at close to $90 a share in early 1997, only to lose over 70 percent of that value by the year's . . .
More holes in social roles
Authors: Douglas T. Kenrick, Vladas Griskevicius
Journal: Behavioral and Brain Sciences (2009)

Abstract Given the strength of Archer's case for a sexual selection account, he is too accommodating of the social roles alternative. We present data on historical changes in violent crime contradicting that perspective, and discuss recent evidence showing how an evolutionary perspective predicts sex similarities and differences responding in a flexible and functional manner to adaptively relevant triggers across different domains.
Vaginal Hemorrhage in Pregnancy
Authors: Delbert Booher, Brian Little
Journal: New England Journal of Medicine (1974)

VAGINAL hemorrhage in a pregnant patient is always a potential emergency. Many perinatal deaths result directly from maternal bleeding with associated intrauterine asphyxia. A larger number result from the sequelae of hypoxia, early delivery and pre-maturity. Clinical management of vaginal bleeding therefore involves consideration of the well-being of both the mother and the fetus.The prognosis of patients who bleed vaginally varies indirectly according to both the amount of bleeding and the length of gestation. Early in pregnancy there is less likelihood of severe hemorrhage with life-threatening loss of blood. Later in pregnancy even mild episodes of bleeding may endanger . . .