tbuckley/cabot-search huggingface dataset:
Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model
Authors: Keiji Hirota, Hiroyuki Yoshitomi, Motomu Hashimoto, Shinji Maeda, Shin Teradaira, Naoshi Sugimoto, Tomoyuki Yamaguchi, Takashi Nomura, Hiromu Ito, Takashi Nakamura, Noriko Sakaguchi, Shimon Sakaguchi
Journal: The Journal of Experimental Medicine (2007)

This report shows that interleukin (IL) 17–producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR) 6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor β and IL-6 additionally need IL-1 and neutralization of interferon (IFN) γ and IL-4 for CCR6 expression. Forced expression of RORγt, a key transcription factor for Th17 cell differentiation, induces not only IL-17 but also CCR6 in naive T cells. Furthermore, Th17 cells produce CCL20, the known ligand for CCR6. Synoviocytes from arthritic joints of mice and humans also produce a large amount of CCL20, with a significant correlation (P = 0.014) between the amounts of IL-17 and CCL20 in RA joints. The CCL20 production by synoviocytes is augmented in vitro by IL-1β, IL-17, or tumor necrosis factor α, and is suppressed by IFN-γ or IL-4. Administration of blocking anti-CCR6 monoclonal antibody substantially inhibits mouse arthritis. Thus, the joint cytokine milieu formed by T cells and synovial cells controls the production of CCL20 and, consequently, the recruitment of CCR6+ arthritogenic Th17 cells to the inflamed joints. These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA.
Short-term intravenous iloprost for treatment of reperfusion lung oedema after pulmonary thromboendarterectomy
Authors: H.-H. Hsu, J.-S. Chen, Y.-S. Chen, W.-J. Ko, S.-W. Kuo, Y.-C. Lee
Journal: Thorax (2007)

This case report describes the treatment of reperfusion lung oedema after pulmonary thromboendarterectomy using intravenous iloprost infusion in a 52-year-old woman diagnosed with chronic thromboembolic pulmonary hypertension.
Single-agent lapatinib for HER2-overexpressing advanced or metastatic breast cancer that progressed on first- or second-line trastuzumab-containing regimens
Authors: K.L. Blackwell, M.D. Pegram, E. Tan-Chiu, L.S. Schwartzberg, M.C. Arbushites, J.D. Maltzman, J.K. Forster, S.D. Rubin, S.H. Stein, H.J. Burstein
Journal: Annals of Oncology (2009)
Oncogene <i>AEG-1</i> Promotes Glioma-Induced Neurodegeneration by Increasing Glutamate Excitotoxicity
Authors: Seok-Geun Lee, Keetae Kim, Timothy P. Kegelman, Rupesh Dash, Swadesh K. Das, Jung Kyoung Choi, Luni Emdad, Eric L. Howlett, Hyun Yong Jeon, Zhao Zhong Su, Byoung Kwon Yoo, Devanand Sarkar, Sung-Hoon Kim, Dong-Chul Kang, Paul B. Fisher
Journal: Cancer Research (2011)

Aggressive tumor growth, diffuse tissue invasion, and neurodegeneration are hallmarks of malignant glioma. Although glutamate excitotoxicity is considered to play a key role in glioma-induced neurodegeneration, the mechanism(s) controlling this process is poorly understood. Astrocyte elevated gene-1 (AEG-1) is an oncogene that is overexpressed in several types of human cancers, including more than 90% of brain tumors. In addition, AEG-1 promotes gliomagenesis, particularly in the context of tumor growth and invasion, 2 primary characteristics of glioma. In the present study, we investigated the contribution of AEG-1 to glioma-induced neurodegeneration. Pearson correlation coefficient analysis in normal brain tissues and samples from glioma patients indicated a strong negative correlation between expression of AEG-1 and a primary glutamate transporter of astrocytes EAAT2. Gain- and loss-of-function studies in normal primary human fetal astrocytes and T98G glioblastoma multiforme cells revealed that AEG-1 repressed EAAT2 expression at a transcriptional level by inducing YY1 activity to inhibit CBP function as a coactivator on the EAAT2 promoter. In addition, AEG-1-mediated EAAT2 repression caused a reduction of glutamate uptake by glial cells, resulting in induction of neuronal cell death. These findings were also confirmed in samples from glioma patients showing that AEG-1 expression negatively correlated with NeuN expression. Taken together, our findings suggest that AEG-1 contributes to glioma-induced neurodegeneration, a hallmark of this fatal tumor, through regulation of EAAT2 expression.
Epirubicin + G-CSF as peripheral blood progenitor cells (PBPC) mobilising agents in breast cancer patients
Authors: G. Rosti, L. Albertazzi, P. Ferrante, P. Nicoletti, P. Morandi, M. Bari, S. Macchi, G. Monti, M. Argnani, L. Sebastiani, M. Marangolo
Journal: Annals of Oncology (1995)

Background: In an attempt to mobilise peripheral blood progenitor cells (PBPC) from patients with breast cancer, Epirubicin supported with G-CSF was tested.Another aim of the study was also to optimize the procedure so that the number of leukapheresis procedures could be reduced.These cells were subsequently reinfused as hematologic rescue after high-dose chemotherapy programs.Patients and methods: Twenty-nine patients received Epirubicin 150 mg/sqm + G-CSF at the dose of 5 |i.g/kg/bw s.c.daily, starting 24 hours after chemotherapy.Twelve had metastatic, eight inflammatory or locally advanced disease, and nine were treated in an adjuvant setting.Results:.The median numbers of CD34+ cells and CFU-GM collected were 12.9 x 10Vkg/bw and 111.7 x 10 4/ kg/ bw, respectively.The mean number of leukapheresis procedures per patient was 1.8 ±0.3 (range 1-3), and the mean day of the first procedure was the tenth ± 1 (range 8-13) after Epirubicin.The minimum required target for one highdose procedure was collected in a single leukapheresis in 13 patients.Moreover, in 9 cases one procedure was adequate for two high-dose courses (i.e.>10 x 10Vkg/bw CD34+ cells).Response to Epirubicin was evaluable in 14/20 cases, with a response rate of 50%.Conclusions: Epirubicin delivered at 150 mg/sqm is a very effective mobilising agent for breast cancer patients; to ameliorate the response rate other active drug(s) should be added.
Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s
Authors: Raffaella Bonecchi, Giancarlo Bianchi, Paola Panina Bordignon, Daniele D'Ambrosio, Rosmarie Lang, Alessandro Borsatti, Silvano Sozzani, Paola Allavena, Patrick A. Gray, Alberto Mantovani, Francesco Sinigaglia
Journal: The Journal of Experimental Medicine (1998)

T helper cells type 1 (Th1s) that produce interferon-γ predominantly mediate cellular immune responses and are involved in the development of chronic inflammatory conditions, whereas Th2s which produce large amounts of IL-4 and IL-5 upregulate IgE production and are prominent in the pathogenesis of allergic diseases. The precise factors determining whether Th1- or Th2-mediated immune responses preferentially occur at a peripheral site of antigen exposure are largely unknown. Chemokines, a superfamily of polypeptide mediators, are a key component of the leukocyte recruitment process. Here we report that among four CXC (CXCR1-4) and five CC (CCR1-5) chemokine receptors analyzed, CXCR3 and CCR5 are preferentially expressed in human Th1s. In contrast, Th2s preferentially express CCR4 and, to a lesser extent, CCR3. In agreement with the differential chemokine receptor expression, Th1s and Th2s selectively migrate in response to the corresponding chemokines. The differential expression of chemokine receptors may dictate, to a large extent, the migration and tissue homing of Th1s and Th2s. It may also determine different susceptibility of Th1s and Th2s to human immunodeficiency virus strains using different fusion coreceptors.
Abnormal postprandial duodenal chyme transport in patients with long standing insulin dependent diabetes mellitus
Authors: H N Nguyen, J Silny, S Wüller, H-U Marschall, G Rau, S Matern
Journal: Gut (1997)

Patients with long standing diabetes mellitus frequently have upper gut dysmotility. Gastroparesis has been well studied, whereas detailed data on duodenal motor function are limited.To characterise postprandial duodenal chyme transport in such patients.Intraluminal multiple impedance measurement, recently introduced as a novel technique for investigation of chyme transport, was used to study postprandial duodenal chyme flow in 10 patients with long standing insulin dependent diabetes mellitus with gastroparesis, and 10 healthy volunteers.Four distinct transport patterns of chyme, termed bolus transport events (BTEs), were found in both groups and could be characterised as: short distance propulsive; simple long distance propulsive; retrograde; and complex long distance propulsive. Diabetic patients had significantly lower numbers of propulsive BTEs (p < 0.01), and higher proportions of retrograde BTEs and complex long distance BTEs (p < 0.05) than control subjects, whereas the proportion of simple long distance BTEs was significantly lower (p < 0.05). The mean propagation velocities of the BTEs were similar in both groups.Abnormal postprandial duodenal chyme transport was found in patients with long standing insulin dependent diabetes mellitus. This is characterised by transport disorganisation and may result in disturbed chyme clearance.
Multiple functional sites on a single Ia molecule defined using T cell clones and antibodies with chain-determined specificity.
Authors: J G Frelinger, M Shigeta, A J Infante, P A Nelson, M Pierres, C G Fathman
Journal: The Journal of Experimental Medicine (1984)

Monoclonal antibodies (mAb) were used to inhibit the proliferation of antigen-reactive (C57BL6/J X A/J)F1 restricted T cell clones. We have been able to subdivide these F1 restricted T cell clones into two groups: one of which recognizes the A alpha k A beta b molecule and the other group which recognizes the A alpha b A beta k molecule. Using clones with defined reactivities, we could assign the reactivities of monoclonals to the A alpha or A beta chains. By immunoprecipitation and two-dimensional analysis of Ia molecules from F1 spleen cells, we could independently map the reactivities of the mAb as being determined by the A alpha or A beta chain. To date, these two methods of chain localization of the antibody reactivity have agreed. Further, the differential blocking of the A alpha k A beta b restricted T cell clones suggests that there exists more than one restriction site per Ia molecule. Increasing the number of possible functional Ia restriction sites, either through combinatorial association of alpha and beta chains or by using more than one site per molecule, should increase the number of ways Ia molecules can function in antigen presentation.
A PREALBUMIN ACTIVATOR OF PREKALLIKREIN
Authors: Allen P. Kaplan, K. Frank Austen
Journal: The Journal of Experimental Medicine (1971)

Activation of a plasma fraction containing unactivated Hageman factor and prekallikrein followed by chromatography of this fraction on DEAE-cellulose revealed four peaks having bradykinin-generating activity. Peak 1 contained kallikrein; peaks 2-3, 4, and 5 each contained prekallikrein-activating activity. Elution of peaks 2-3, 4, and 5 from disc gels after electrophoresis at pH 9.3 revealed peaks of prekallikrein-activating activity located at 5-8, 11-12, 15-16, and 20-26 mm, each of which was associated with a peak of clot-promoting activity which specifically corrected Hageman factor deficiency. Conversion of peak 2 to peaks 3, 4, and 5 was associated with a progressive decrease in size, increase in net negative charge, increased prekallikrein-activating activity, and decreased ability to correct Hageman factor deficiency. Plasminogen and plasmin were found on a DEAE-cellulose chromatogram of serum overlapping peaks 2 and 3. Incubation of active Hageman factor with streptokinase-activated plasminogen resulted in enhanced ability of the mixture to activate prekallikrein. Assessment of the products of this reaction by disc gel electrophoresis demonstrated the formation of the prealbumin prekallikrein activator corresponding to the major prekallikrein activator generated by contact activation of human plasma. The conversion of plasminogen to plasmin and the subsequent cleavage of Hageman factor by plasmin to form activators of prekallikrein represents one pathway in which coagulation, fibrinolysis, and inflammation are linked.
Translating the A1C Assay Into Estimated Average Glucose Values
Authors: David M. Nathan, Judith Kuenen, Rikke Borg, Hui Zheng, David Schoenfeld, Robert J. Heine
Journal: Diabetes Care (2008)

The A1C assay, expressed as the percent of hemoglobin that is glycated, measures chronic glycemia and is widely used to judge the adequacy of diabetes treatment and adjust therapy. Day-to-day management is guided by self-monitoring of capillary glucose concentrations (milligrams per deciliter or millimoles per liter). We sought to define the mathematical relationship between A1C and average glucose (AG) levels and determine whether A1C could be expressed and reported as AG in the same units as used in self-monitoring.
Superior effects of high-dose enzyme replacement therapy in type 1 Gaucher disease on bone marrow involvement and chitotriosidase levels: a 2-center retrospective analysis
Authors: Maaike de Fost, Carla E. M. Hollak, Johanna E. M. Groener, Johannes M. F. G. Aerts, Mario Maas, Ludger W. Poll, Maaike G. Wiersma, Dieter Häussinger, Sarah Brett, Nicole Brill, Stephan vom Dahl
Journal: Blood (2006)
Limitation of cigarette consumption by CYP2A6*4, *7 and *9 polymorphisms
Authors: N. Minematsu, H. Nakamura, M. Furuuchi, T. Nakajima, S. Takahashi, H. Tateno, A. Ishizaka
Journal: European Respiratory Journal (2006)

The whole gene deletion CYP2A6*4 , the defect of the main nicotine oxidase, contributes to limiting lifelong and daily cigarette consumption. However, the effects on smoking habits of CYP2A6*7 and *9 , two major functional polymorphisms common in Asian populations, have not been reported. The present study examined the relationship between polymorphisms *4 , *7 and *9 with the smoking habits of 200 Japanese smokers who visited the Keio University Hospital (Tokyo, Japan). The allele frequencies of *1 (wild type), *4 , *7 and *9 were 52, 17, 11 and 20%, respectively. When the three polymorphisms were considered simultaneously, the percentages of homozygous wild type, heterozygote, and homozygous mutants and compound heterozygotes were 26.0, 52.5 and 21.5%, respectively. Homozygous mutants and compound heterozygotes (n = 43) smoked fewer cigarettes daily than heterozygotes (n = 105) and homozygous wild-type individuals (n = 52). Smokers with *7 / *7 , *9/*9 or *7 / *9 had lower daily cigarette consumption than smokers with *1/*1 . In conclusion, polymorphisms *4 , *7 and *9 of CYP2A6 were detected in approximately three out of four Japanese smokers, and their daily cigarette consumption was genetically modulated by these functional polymorphisms.
Hyperkalemia in end-stage renal disease
Authors: M Allon
Journal: Journal of the American Society of Nephrology (1995)

Clinical investigations in the past few years have enhanced the understanding of the mechanisms of hyperkalemia in patients with ESRD. The results of these studies have led to modifications in the acute treatment and prevention of hyperkalemia in this patient population. They have confirmed the efficacy of intravenous insulin, while raising doubts about the utility of intravenous bicarbonate, for the acute treatment of hyperkalemia. Moreover, the beta-adrenergic agonist albuterol has been shown to be a useful adjunct to insulin for acutely lowering plasma potassium. Finally, there has been enhanced recognition of nondietary factors that can predispose to hyperkalemia in patients with ESRD, including prolonged fasting and the use of nonselective beta-adrenergic blockers. These new insights may improve the clinical management of hyperkalemia in patients with renal failure.
Integration of Antiretroviral Therapy with Tuberculosis Treatment
Authors: Salim S. Abdool Karim, Kogieleum Naidoo, Anneke Grobler, Nesri Padayatchi, Cheryl Baxter, Andrew L. Gray, Tanuja Gengiah, Santhanalakshmi Gengiah, Anushka Naidoo, Niraksha Jithoo, Gonasagrie Nair, Wafaa M. El-Sadr, Gerald Friedland, Quarraisha Abdool Karim
Journal: New England Journal of Medicine (2011)

We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, the timing for the initiation of ART during tuberculosis treatment remains unresolved.We conducted a three-group, open-label, randomized, controlled trial in South Africa involving 642 ambulatory patients, all with tuberculosis (confirmed by a positive sputum smear for acid-fast bacilli), human immunodeficiency virus infection, and a CD4+ T-cell count of less than 500 per cubic millimeter. Findings in the earlier-ART group (ART initiated within 4 weeks after the start of tuberculosis treatment, 214 patients) and later-ART group (ART initiated during the first 4 weeks of the continuation phase of tuberculosis treatment, 215 patients) are presented here.At baseline, the median CD4+ T-cell count was 150 per cubic millimeter, and the median viral load was 161,000 copies per milliliter, with no significant differences between the two groups. The incidence rate of the acquired immunodeficiency syndrome (AIDS) or death was 6.9 cases per 100 person-years in the earlier-ART group (18 cases) as compared with 7.8 per 100 person-years in the later-ART group (19 cases) (incidence-rate ratio, 0.89; 95% confidence interval [CI], 0.44 to 1.79; P=0.73). However, among patients with CD4+ T-cell counts of less than 50 per cubic millimeter, the incidence rates of AIDS or death were 8.5 and 26.3 cases per 100 person-years, respectively (incidence-rate ratio, 0.32; 95% CI, 0.07 to 1.13; P=0.06). The incidence rates of the immune reconstitution inflammatory syndrome (IRIS) were 20.1 and 7.7 cases per 100 person-years, respectively (incidence-rate ratio, 2.62; 95% CI, 1.48 to 4.82; P<0.001). Adverse events requiring a switching of antiretroviral drugs occurred in 10 patients in the earlier-ART group and 1 patient in the later-ART group (P=0.006).Early initiation of ART in patients with CD4+ T-cell counts of less than 50 per cubic millimeter increased AIDS-free survival. Deferral of the initiation of ART to the first 4 weeks of the continuation phase of tuberculosis therapy in those with higher CD4+ T-cell counts reduced the risks of IRIS and other adverse events related to ART without increasing the risk of AIDS or death. (Funded by the U.S. President's Emergency Plan for AIDS Relief and others; SAPIT ClinicalTrials.gov number, NCT00398996.).
Responding to the global human resources crisis
Authors: Vasant Narasimhan, Hilary Brown, Ariel Pablos-Mendez, Orvill Adams, Gilles Dussault, Gijs Elzinga, Anders Nordstrom, Demissie Habte, Marian Jacobs, Giorgio Solimano, Nelson Sewankambo, Suwit Wibulpolprasert, Timothy Evans, Lincoln Chen
Journal: The Lancet (2004)
Postconditioning: A Form of “Modified Reperfusion” Protects the Myocardium by Activating the Phosphatidylinositol 3-Kinase-Akt Pathway
Authors: Andrew Tsang, Derek J. Hausenloy, Mihaela M. Mocanu, Derek M. Yellon
Journal: Circulation Research (2004)

Brief intermittent episodes of ischemia and reperfusion, at the onset of reperfusion after a prolonged period of ischemia, confer cardioprotection, a phenomenon termed "ischemic postconditioning" (Postcond). We hypothesized that this phenomenon may just represent a modified form of reperfusion that activates the reperfusion injury salvage kinase (RISK) pathway. Isolated perfused rat hearts were subjected to: (a) 35 minutes of ischemia and 120 minutes of reperfusion, and infarct size was determined by tetrazolium staining; or (b) 35 minutes of ischemia and 7 minutes of reperfusion, and the phosphorylation states of Akt, endothelial NO synthase (eNOS), and p70S6K were determined. Postcond reduced infarct size from 51.2+/-3.4% to 31.5+/-4.1% (P<0.01), an effect comparable with ischemic preconditioning (IPC; 27.5+/-2.3%; P<0.01). Of interest, the combined protective effects of IPC and Postcond were not additive (30.1+/-4.8% with IPC+Postcond; P=NS). Inhibiting phosphatidylinositol 3-kinase (PI3K) at reperfusion using LY or Wortmannin (Wort) during the first 15 minutes of reperfusion completely abolished Postcond-induced protection (31.5+/-4.1% with Postcond versus 51.7+/-4.5% with Postcond+LY, P<0.01; 56.2+/-10.1% with Postcond+ Wort; P<0.01), suggesting that Postcond protects the heart by activating PI3K-Akt. Western blot analysis demonstrated that Postcond induced a significant increase in phosphorylation of Akt, eNOS, and p70S6K in an LY- and Wort-sensitive manner. In conclusion, we show for the first time that ischemic Postcond protects the myocardium by activating the prosurvival kinases PI3K-Akt, eNOS, and p70S6K in accordance with the RISK pathway.
Underuse of Breast Cancer Adjuvant Treatment: Patient Knowledge, Beliefs, and Medical Mistrust
Authors: Nina A. Bickell, Jessica Weidmann, Kezhen Fei, Jenny J. Lin, Howard Leventhal
Journal: Journal of Clinical Oncology (2009)

Purpose Little is known about why women with breast cancer who have surgery do not receive proven effective postsurgical adjuvant treatments. Methods We surveyed 258 women who recently underwent surgical treatment at six New York City hospitals for early-stage breast cancer about their care, knowledge, and beliefs about breast cancer and its treatment. As per national guidelines, all women should have received adjuvant treatment. Adjuvant treatment data were obtained from inpatient and outpatient charts. Factor analysis was used to create scales scored to 100 of treatment beliefs and knowledge, medical mistrust, and physician communication about treatment. Bivariate and multivariate analyses assessed differences between treated and untreated women. Results Compared with treated women, untreated women were less likely to know that adjuvant therapies increase survival (on a 100-point scale; 66 v 75; P &lt; .0001), had greater mistrust (64 v 53; P = .001), and had less self-efficacy (92 v 97; P &lt; .05); physician communication about treatment did not affect patient knowledge of treatment benefits (r = 0.8; P = .21). Multivariate analysis found that untreated women were more likely to be 70 years or older (adjusted relative risk [aRR], 1.11; 95% CI, 1.00 to 1.13), to have comorbidities (aRR, 1.10; 95% CI, 1.04 to 1.12), and to express mistrust in the medical delivery system (aRR, 1.003; 95% CI, 1.00 to 1.007), even though they were more likely to believe adjuvant treatments were beneficial (aRR, 0.99; 95% CI, 0.98 to 0.99; model c, 0.84; P ≤ .0001). Conclusion Patient knowledge and beliefs about treatment and medical mistrust are mutable factors associated with underuse of effective adjuvant therapies. Physicians may improve cancer care by ensuring that discussions about adjuvant therapy include a clear presentation of the benefits, not just the risks of treatment, and by addressing patient trust in and concerns about the medical system.