tbuckley/cabot-search huggingface dataset:
A2.39 Cytokine-induced regulation of human TH17 differentiation
Authors: E Baricza, E Lajkó, L Kőhidai, B Molnár-Érsek, N Marton, E Buzás, G Nagy
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Th17 cells have a central role in the inflammation via their pro-inflammatory cytokine production, such as interleukin (IL)-17A, -17F, -21, -22, and tumour necrosis factor-α. We studied <i><i>in vitro</i></i> Th17 cell differentiation of healthy donors and patients with rheumatoid arthritis (RA). <h3>Materials and methods</h3> CD45RO- and CD45RO+ cells were isolated from peripheral blood mononuclear cells with a two-step negative magnetic separation method. The cells were activated with anti-CD3 and anti-CD28 antibodies and treated with TGF<sub>β</sub> (2.5 ng/ml), IL-6 (25 ng/ml), IL-1<sub>β</sub> (10 ng/ml) and IL-23 (10 ng/ml) cytokines and with anti-IL-4 (10 μg/ml) blocking antibody. After 5 and 10 days the IL-17 and IL-22 production were measured by ELISPOT and ELISA; the RORc and Tbet expression were measured by quantitative real-time PCR. Cell viability was monitored by impendance-based cell analyzer (CASY-TT). <h3>Results</h3> Although the anti-CD3/CD28 activation increased the IL-17 and IL-22 production; it did not alter the RORc expression of the CD45RO- cells of healthy donors. The IL-22 production and the Tbet expression of the RORc producing cells were inhibited by TGF<sub>β </sub>and stimulated by IL-23 treatment. The CD45RO+ cells of healthy donors expressed higher level of RORc and T-bet without stimulation or cytokine treatment and also higher amount of IL-17 compared to the CD45RO- cells. By contrast, there was no difference between the RORc expression of the freshly separated CD45RO+ and CD45RO- cells of RA patients. The production of IL-17 and IL-22 of the differentiated CD45RO- cells from RA patients were both increased by IL-23 treatment. <h3>Conclusions</h3> The IL-17 and IL-22 production are differently regulated during the human Th17 differentiation. Furthermore, our present data suggest that the increased baseline RORc expression of the CD45RO- cells may contribute to the accelerated Th17 differentiation in RA.
Selective Expression of Purkinje-Cell Antigens in Tumor Tissue from Patients with Paraneoplastic Cerebellar Degeneration
Authors: Henry M. Furneaux, Marc K. Rosenblum, Josep Dalmau, Ellen Wong, Prescot Woodruff, Francesc Graus, Jerome B. Posner
Journal: New England Journal of Medicine (1990)

Paraneoplastic cerebellar degeneration is a rare syndrome that occurs in patients with gynecologic cancer and is characterized by widespread loss of Purkinje cells. To determine whether Purkinje-cell antigens are selectively expressed in the tumors of patients with the syndrome, we examined tumor tissue from 10 patients whose serum contained anti—Purkinje-cell (anti-Yo) antibodies. The origins of the cancers were the breast (five patients), ovary (three), endometrium (one), and fallopian tube (one). We used as controls tumor tissue from 11 patients with ovarian cancer and 10 patients with breast cancer who were neurologically normal.
The utility of preoperative breast magnetic resonance imaging in invasive breast cancer according to HER2 status.
Authors: SA McLaughlin, LA Vallow, SL Hines, W Tan
Journal: Cancer Research (2009)

Abstract Abstract #4020 Background: HER2 positive (HER2+) breast cancer accounts for 20% of all breast cancer and is an independent adverse prognostic factor. Breast magnetic resonance imaging (MRI) has been shown to identify additional mammographically occult ipsilateral (I/L) and contralateral (C/L) disease, however indications for preoperative MRI in patients with newly diagnosed breast cancer are not standardized. While invasive lobular cancer, younger patient age, and increased breast density have been suggested as routine indications, the role of preoperative MRI according to HER2 status has not been evaluated.&amp;#x2028; Methods: All patients with invasive breast cancer who underwent preoperative MRI between January 2003 and December 2007 were reviewed. Retrospective chart review was performed to collect clinical, radiographic, and pathologic data. The incidence of additional I/L or C/L malignacy was calculated. Additionally, changes in surgical management because of MRI findings were recorded.&amp;#x2028; Results: Of the 401 women with invasive breast cancer undergoing preoperative breast MRI, 51 (13%) had HER2+ tumors. The average age at the time of MRI was similar in both groups. HER2+ patients were more likely to have nodal disease, and tumors with higher rates of lymphovascular invasion or extensive intraductal components.&amp;#x2028; &amp;#x2028; When compared to HER2- patients, more HER2+ patients had additional ipsilateral MRI abnormalities. A second ipsilateral cancer was found in 31% of HER2+ patients compared to 25% of HER2- patients. When analyzed according to ER status, HER2+/ ER- patients were more likely to have an additional site of cancer compared to HER2+/ER+ patients (42% vs 23%). Conversely, among HER2- patients, rates of additional ipsilateral cancer were similar for HER2-/ER+ (26%) and HERr2-/ER- (23%) patients. Of the 216 patients (HER2+ and HER2-) with additional ipsilateral MRI findings (benign or malignant), 125/216 (58%) patients were deemed appropriate breast conservation (BCT) candidates after MRI. However, BCT was only chosen in 84/125 (67%) patients. Additional contralateral disease was documented in 8% of HER2+ versus 5% of HER2- patients.&amp;#x2028; Conclusions: HER2 positivity remains and important prognostic factor for women with breast cancer. Indications for routine preoperative MRI are unclear. In patients with newly diagnosed Her2+ invasive breast cancer routine preoperative MRI may be valuable in the subset of patients who are also ER-. Further study is needed to determine the influence of MRI on patient decisions for surgical therapy. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4020.
Myocardial Ischemia after Ligation of an Anomalous Left Coronary Artery Arising from the Pulmonary Artery
Authors: Nosrat A. Massih, John Lawler, Margaret Vermillion
Journal: New England Journal of Medicine (1963)

ALTHOUGH origin of the left coronary artery from the pulmonary artery is not a newly recognized anomaly, until recent years the direction of blood flow in this particular anatomic condition was a matter of dispute. Brooks,1 in 1886, suggested the presence of a left-to-right shunt on the basis of postmortem examination in 2 cases. Later, Abbott2 and, more recently, Edwards3 have emphasized the probable retrograde flow from coronary artery to pulmonary artery. A left-to-right shunt has now been clearly demonstrated by cardiac catheterization and retrograde angiography.4 5 6 7 The direction of the shunt has also been shown on the operating table.8 Because . . .
Case 12-2002
Authors: J. Dick MacLean, Fiona M. Graeme-Cook
Journal: New England Journal of Medicine (2002)

Presentation of CaseA 50-year-old man was admitted to the Tropical and Geographic Medicine Center of this hospital because of eosinophilia and fluctuating hepatic lesions.The patient had been well until 10 months earlier, when he was splashed in the face while brushing his dog's teeth. He subsequently noted a sore on the left side of his nose, which progressed to a frank abscess. The abscess resolved with the administration of cephalexin, but diffuse myalgias, sweats, and headache soon developed, accompanied by fever (temperature, up to 40°C) and a rash on the legs that progressed to the trunk. The rash . . .
Tl-201 Myocardial SPECT in Patients With Systemic Arterial Diseases
Authors: YUJI MURATA, ICHIRO YAMADA, ISAO UMEHARA, HITOSHI SHIBUYA
Journal: Clinical Nuclear Medicine (1998)

We compared the results of Tl-201 myocardial SPECT of patients with arteriosclerosis obliterans (ASO), abdominal aortic aneurysm (AAA), and Takayasu arteritis (TA), so that coronary artery disease could be evaluated in them. Twenty-three patients (ASO, 9; AAA, 8; TA, 6) had Tl-201 myocardial SPECT with stress testing, and SPECT data was assessed qualitatively and quantitatively. Qualitative analysis showed that myocardial perfusion was decreased most in patients with ASO, followed by patients with AAA, and was minimally decreased in patients with TA. Quantitative analysis indicated that segmental uptake was significantly less in four segments in ASO compared with TA, less in two segments in AAA compared with TA, and less in two segments in ASO compared with AAA. Thus patients with ASO and AAA were found to have a marked abnormality in Tl-201 myocardial SPECT, indicating that this procedure should be performed in these patients. In patients with TA, however, because of minimal abnormality in myocardial perfusion, the role of SPECT is limited.
Abstract P2-02-03: The Collagen Receptor Endo180: A Metastatic Plasma Marker In Breast Cancer Modulated By Bisphosphonate Treatment
Authors: J Sturge, MP Caley, K Purshouse, A-V Fonseca, M Rodriguez-Teja, G Kogianni, J Waxman, C Palmieri
Journal: Cancer Research (2012)

Abstract Purpose: To establish whether the collagen remodelling receptor, Endo180, should be given consideration as a useful plasma marker in metastatic breast cancer. Patients and Methods: Analysis of MCF-7 and MDA-MB-231 cell conditioned medium validated the anti-human (39.10) monoclonal antibody as suitable for the detection of soluble Endo180 in plasma. Eighty-seven breast cancer patients with early primary, locally advanced and metastatic disease were included in the study. Correlations between Endo180, CA 15–3 antigen (MUC1; mucin 1) and bisphosphonate treatment were investigated. Results: Endo180 was elevated in metastatic compared to early breast cancer (P &amp;lt;.0001) and was able to differentiate locoregional disease and visceral and/or osseous metastasis (P = .0005). In combination CA 15–3 antigen (cut-off: 28 U/mL) and Endo180 (relative plasma level cut-off range: 0.95–1.65) had sensitivity of 94–97% and specificity of 52–68%. Endo180 levels were significantly higher in patients who were treatment naive (2.17 ± 0.82, N = 13) compared to those previously (1.82 ± 0.33, N = 5) or currently (1.37 ± 0.74, N = 24) receiving bisphosphonates (P = .011). In the bisphosphonate naive setting (N = 57) the combination of Endo180 (relative plasma level cut-off range: 0.95–1.65) and CA 15–3 antigen (cut-off: 28 U/mL) had a sensitivity of 87–92% and specificity of 72–79%. Conclusion: Endo180 is a plasma marker with high sensitivity in metastatic breast cancer that can be modulated by bisphosphonate treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-02-03.
ED-29 * THE INCIDENCE OF ADULT AND PEDIATRIC INTRACRANIAL EPENDYMOMAS WITHIN THE SCOTT AND WHITE INTEGRATED HEALTHCARE SYSTEM
Authors: R. Shephard, S. Singel, E. Fonkem
Journal: Neuro-Oncology (2014)

INTRODUCTION: Ependymomas are characterized by their higher incidence in children and by their rarity, especially among adult groups. Indeed, it has been difficult to reach a consensus on the most effective treatments. The purpose of this study was to determine how the outcome of adult and pediatric ependymomas is affected by various factors including age, ethnicity, tumor grade, and tumor type. METHODS: We conducted a retrospective analysis of ependymoma patients within the Scott and White brain tumor registry from 1976-2011. Data was analyzed regarding age, ethnicity, treatment interval, geographic distribution, tumor grade (Grade I - anaplastic), and tumor type (ependymoma and subependymoma). Analyses included univariate and multivariate methods. RESULTS: This study includes 28 patients within the Scott and White brain tumor registry from 1976-2011. All of the patients were subject to the same analyses. Of those 28 patients, 5 had subependymomas. 0f the 23 ependymoma cases, 2 were anaplastic. The remaining were either Grade I or Grade II. 19 of the 28 patients, or 68%, were of white ethnicity, the remainder of black, Hispanic, or other/unknown ethnicity. Additionally, 40% of the subependymoma patients were of white ethnicity. Survival rates were found to be in concordance with the current standards: 40-65% for pediatric cases and 55-90% for adult cases. We observed no death among the subependymoma group and thus a concurrent increase in the median survival of this group. The median survival time of the anaplastic ependymoma group was more difficult to quantify due to a limited number of cases and because the patients of this group are still alive. CONCLUSION: This study suggests that age is intimately involved with the development of ependymomas and subependymomas. White/Caucasian ethnicity also seems to correlate with the growth of subependymomas and ependymomas moreso than is seen in the other ethnicities of this study.
Interaction between Chloral Hydrate and Warfarin
Journal: New England Journal of Medicine (1972)

Data from a comprehensive drug surveillance program were analyzed to determine the clinical importance of the interaction between chloral hydrate and the oral anticoagulant warfarin. Patients anticoagulated during hospitalization were divided into three groups receiving continuous, occasional or no chloral hydrate during the first four days of warfarin therapy. Those receiving continuous chloral hydrate therapy required significantly less warfarin (p <0.01) during the induction phase of anticoagulation than those receiving no chloral hydrate. Patients given occasional chloral hydrate required an intermediate dose. All patients received similar loading doses of warfarin and similar doses from the fifth day onward. The results indicate that the interaction between these drugs is of clinical importance and that care should be exercised when they are administered concurrently.
Lingual Tonsillar Metastasis From Rectal Carcinoma
Authors: Minggang Su, Chong Jiang, Lin Li, Fanglan Li, Rong Tian
Journal: Clinical Nuclear Medicine (2014)

A 66-year-old man presenting with sacral pain 18 months after radical transabdominal resection of rectal mucinous adenocarcinoma underwent F-FDG PET/CT cancer surveillance. Detection of multiple nodules in lingual tonsil and left neck by imaging initially suggested tonsillar squamous carcinoma (as a second primary) with spread to cervical nodes, given the rarity with which rectal carcinoma metastasizes to the head and neck. Ultimately, the tonsillar neoplasm proved to be adenocarcinoma of colorectal origin based on its shared histologic features and compatible immunostaining profile.
Sleep-disordered Breathing in Pregnancy
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Sleep disordered breathing is under recognized in pregnant women. Women affected by SDB or obstructive sleep apnea (OSA) are more likely to experience pregnancy complications and adverse pregnancy outcomes including preeclampsia, preterm birth, and cesarean delivery. The risk factors for sleep disordered breathing and OSA are include: older age, obesity, African-American race, craniofacial abnormalities, and smoking. Women with known SDB/OSA who become pregnant should be evaluated by a sleep medicine specialist to optimize CPAP settings. During labor, pain relief strategies which limit the use of opioid medications should be employed in order to reduce the risk of respiratory suppression. Untreated sleep apnea is associated with subsequent diabetes, hypertension and fatal and nonfatal cardiovascular disease. Management of SDB in pregnant women should address both short term and long term risks of the disease.
Implementation of HIV testing is patchy in the UK
Authors: R. Elmahdi, H. Ward, G. Cooke, S. Fidler
Journal: BMJ (2014)

The clinical review on HIV testing and management is welcome and timely.1 Since the publication of guidelines on testing in 2008, implementation has been patchy. We recently conducted a systematic review of implementation of these guidelines in the UK; the overall estimate of test coverage was only 27.2% (95% CI 22.4% to 32%) in eligible populations outside of antenatal and sexual health …
Abstract 614: ErbB-2 Suppresses Notch-1 Signaling by Regulating Jagged-1 Localization in ErbB-2 positive breast cancer
Authors: Kinnari Mehta, Kathleen Meeke, Parul Patel, Lucio Miele, Clodia Osipo
Journal: Cancer Research (2010)

Abstract ErbB-2 is amplified and overexpressed in 20-30% of breast tumors. Today, ErbB-2 positive breast cancers are treated with trastuzumab plus chemotherapy. In spite of dramatic improvements in survival for women with ErbB-2+ breast tumors, resistance remains a major problem in metastatic disease. We have recently published that ErbB-2 suppresses Notch-1 activity and this is reversed by trastuzumab or a dual EGFR/ErbB-2 tyrosine kinase inhibitor similar to lapatinb. Furthermore, we demonstrated that trastuzumab resistance is reversed with a Notch-1 siRNA or a gamma-secretase inhibitor (GSI). Coincidentally, co-overexpression of Notch-1 and its ligand, Jagged-1, in breast cancer have been associated with the poorest overall survival. We know that activated Notch-1 plays an important role in ErbB-2 positive breast cancer and trastuzumab resistance; however, the precise mechanism by which Notch-1 is activated is not yet known. Thus, we hypothesized that overexpression of ErbB-2 inhibited expression and/or cell surface localization of Jagged-1 to suppress Notch-1 activity. This would be reversed in response to anti-ErbB-2 treatment. The results demonstrated that trastuzumab or lapatinib treatment of SKBr3 cells increased protein expression of Jagged-1 by Flow Cytometry. Notch-1 and Jagged-1 co-localized with early endosome antigen-1 (EEA-1) to submembraneous endosomes in ErbB-2 positive breast cancer cells as measured by confocal immunofluorescence. However upon trastuzumab treatment, Notch-1 and Jagged-1 exited EEA-1 positive vesicles and Notch-1 accumulated in the nucleus while Jagged-1 localized to the cell membrane. Cell surface biotinylation assays showed that Jagged-1 was enriched on the cell surface in response to trastuzumab treatment and this was mimicked by expression of K44A Dynamin. Cell surface accumulation of Jagged-1 was associated with an increase in Notch-1 transcriptional activity as measured by an increase in Deltex1 mRNA by real-time PCR. Conversely, knockdown of Jagged-1 by siRNA in SKbr3 and BT474 cells prevented the trastuzumab-induced increase in Deltex1 mRNA. Co-culture studies confirmed that culturing SKBr3 cells with fibroblast-expressing Jagged-1 or DLL4 increased Notch activity as measured by a CBF-1/Notch reporter assay. Taken together, these results suggest that ErbB-2 suppresses Notch-1 activity by retention of Jagged-1 or possibly other Notch ligands within early endosomes, which may be reversed by trastuzumab or lapatinib treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 614.
Inhaled Glucocorticoids for Asthma
Authors: Peter J. Barnes
Journal: New England Journal of Medicine (1995)

Glucocorticoids are the most effective therapy available for patients with asthma. They may be administered either orally or, much more safely, by inhalation. With the recognition that airway inflammation is present even in patients with mild asthma, therapy with inhaled glucocorticoids is now recommended at a much earlier stage.1 However, despite their proved efficacy in the treatment of asthma, enthusiasm for their use has been tempered by concern about systemic side effects. Because of this concern, less effective therapies are often preferred, particularly for children.Mechanism of ActionMolecular MechanismsInhaled glucocorticoids are highly lipophilic. They rapidly enter airway cells, . . .
Abstract 4884: The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation
Authors: Ahmed Y. Ali, Mohammad R. Abedini, Benjamin K. Tsang
Journal: Cancer Research (2012)

Abstract Cisplatin (CDDP: cis-diamminedichloroplatinum) resistance is a major hurdle in the treatment of human ovarian cancer (OVCA). A better understanding of the mechanisms of CDDP resistance can greatly improve therapeutic outcome for patients. p53, a determinant of CDDP sensitivity in ovarian cancer, is activated by Chk1 in response to DNA damage. Although the oncogenic phosphatase Protein Phosphatase Magnesium-dependent 1 (PPM1D) can deactivate both p53 and Chk1 through site-specific dephosphorylation, whether PPM1D plays a role in CDDP resistance is unknown. Here, using pair-matched wt-p53 CDDP-sensitive (OV2008) and -resistant (C13*) cells, and p53-compromised CDDP-resistant cells (A2780cp, OCC-1, OVCAR-3, and SKOV3), we have demonstrated (i) the existence of site-specific differences in phospho-Ser-Checkpoint kinase 1 (Chk1) content between sensitive and resistant cells in response to CDDP; (ii) PPM1D, but not phosphoinositide-3-kinase-related kinase (ATR), is important in the regulation of CDDP-induced Chk1 activation and ovarian cancer cell chemosensitivity; (iii) PPM1D down-regulation sensitizes resistant cells to CDDP primarily by activating Chk1 and p53. Our findings establish for the first time that PPM1D confers CDDP resistance in ovarian cancer cells through attenuating CDDP-induced, Chk1-mediated, p53-dependent apoptosis. These findings extend the current knowledge on the molecular and cellular basis of cisplatin resistance and offer the rationale for PPMID as a potential target for treatment of chemoresistant ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4884. doi:1538-7445.AM2012-4884