tbuckley/cabot-search huggingface dataset:
P603ADMA in pericardial fluid of patients may be a biomarker of cardiac hypertrophy
Authors: Z Nemeth, A Cziraki, S Szabados, F Springman, B Biri, S Keki, A Koller
Journal: Cardiovascular Research (2014)

Purpose: Pericardial fluid (PF) contains biologically active substances, such as the L-arginine and its methylated derivative asymmetric dimethylarginine (ADMA). L-arginine is the substrate of nitric oxide synthase (NOS) producing NO, which has been implicated in cardiac remodeling, whereas ADMA interferes with NO bioavailability. Thus we hypothesized that L-arginine and ADMA present in PF of patients undergoing coronary artery bypass graft (CABG) or valve replacement (VR) surgery, and their levels correlate with the morphology of the heart. Methods L-arginine and ADMA concentrations were determined in plasma and PF of patients undergoing CABG (n=26) or VR (n=23) surgery. Morphological parameters of the chambers of the heart were examined by 2-D echocardiography. Results: In both groups, the levels of both plasma and PF L-arginine were higher than that of ADMA (CABG, plasma: 74.7±4.6 μmol/L vs. 0.7±0.1 μmol/L, PF: 76.1±4.7 μmol/L vs. 0.7±0.0 μmol/L; VR, plasma: 58.4±5.4 μmol/L vs. 0.8±0.0 μmol/L, PF: 75.1±5.3 μmol/L vs. 0.9±0.0 μmol/L; p<0.05). The PF ADMA was higher in the VR than CABG group (0.9±0.0 μmol/L vs. 0.7±0.0 μmol/L; p<0.05). The thickness of interventricular septum (IVS) and the posterior wall (PW), as well as the right ventricular (RV) and right atrial (RA) and the left atrial (LA) areas were higher in VR compared to CABG group. In addition, the left ventricular mass (LVM) was higher in the VR compared to the CABG group. In the VR group, we found a positive correlation between the level of PF ADMA and the left ventricular end-systolic diameter (Ds), the left ventricular end-diastolic diameter (Dd), the RV, and the LVM. Conclusions: The elevated concentration of ADMA in the pericardial fluid indicates a reduced level of NO, which may be responsible for the development of cardiac hypertrophy, especially in patients with valve replacement. Thus ADMA could be an additional biomarker of cardiac hypertrophy.
Detection of nondisjunction in mammals.
Authors: I Hansmann, H D Probeck
Journal: Environmental Health Perspectives (1979)

Methods have been developed in the past to assess spontaneous and induced chromosomal aneuploidy in germ cells and in early pre- and postimplantation mammalian embryos. Some of these methods yield still more information when combined with chromosome banding techniques. Various chemicals and x-rays have been tested in mammalian oogenesis and x-rays in spermatogenesis. The inference may be drawn from these studies that spontaneous nondisjunction is considered to occur only rarely in mouse and hamster oogenesis and spermatogenesis. X-rays induce nondisjunction during male and femlae meiosis, thus giving rise to significantly more aneuploid oocytes and F1 embryos. The alkylating agents trenimone and cyclophosphamide induce chromosomal missegregation in oocytes; the incidence depends on the dose injected. Hormones used as oral contraceptives did cause aneuploidy in oocytes, but only after daily treatment with high doses. Hormones used for stimulated ovulation did not interfere with chromosome segregation in the mouse and Chinese and Syrian hamsters. The following problems may be considered in futre studies: the problem of a species-specificity for induced nondisjunction; the question of a stage sensitivity (transplacental treatment); what happens after chronic exposure, also at low doses; the presence of a threshold; the existence of a dose-effect relation; the nature of cellular target(s) responsible for induced nondisjunction (spindle, regulatory proteins for polymerization of microtubules and ther depolymerization, centrioles, centromeres, RNA, or gene expression); whether DNA is involved and whether repair capacity plays a role.
Case 15-1969
Authors: Jacob Lerman, Benjamin Castleman
Journal: New England Journal of Medicine (1969)

Presentation of Case First admission. A thirty-six-year-old man was admitted to the hospital because of pain in the joints.Five years previously he had an episode of pain, redness and swelling in the right wrist; the uric acid was 11.6 mg per 100 ml. With probenecid and phenylbutazone therapy the symptoms subsided, and the uric acid decreased to 5 mg per 100 ml. One year before entry rhinorrhea occurred, and bilateral otitis and mastoiditis were found at another hospital; purulent material was drained from each ear. Two months later left pleuritic pain associated with a nonproductive cough developed; an x-ray . . .
STUDIES ON THE CORPUS CALLOSUM
Authors: ANDREW J. E. AKELAITIS
Journal: American Journal of Psychiatry (1941)

In two epileptics with "psychic equivalents" no change in behavior during the convulsive-free periods or in the equivalent state was observed following partial or complete section of the corpus callosum. In one epileptic with a chronic invalid reaction no change was observed following partial section of the corpus callosum. In a fourth mentally retarded epileptic with compulsive-obsessive behavior and suicidal and combative tendencies the improvement which occurred cannot be directly related to the partial sectioning of the corpus callosum. In conclusion, no obvious change in the various manifestations of personality under the changing conditions found in epilepsy could be discerned following partial or complete section of the corpus callosum.
Abstract 4409: A quantitative MSD assay to measure c-IAP1 degradation in PBMC, cell lines and tumor cells as a pharmacodynamic biomarker following antagonism of IAP family members
Authors: Edward E. Kadel, Kristina West, Erin McNamara, Justin Low, Mehraban Khosraviani, Michael Mamounas, Wayne J. Fairbrother, Walter C. Darbonne
Journal: Cancer Research (2011)

Abstract The Inhibitor of Apoptosis (IAP) protein family members are widely expressed in many cancers, providing a mechanism to protect these cancer cells from apoptosis. The IAP proteins block activation of the canonical and non-canonical NF-kB pathway, the subsequent expression of TNFα and its initiation of the extrinsic apoptosis pathway. IAP proteins also directly bind and inhibit caspases activated during the induction of apoptosis. Using MDA-MB-231 cells as a model system to assess the effect of candidate IAP antagonists on markers of extrinsic and intrinsic pathway inhibition, we observe that the antagonism of the major IAP family members results in apoptosis in vitro and inhibits their tumor growth in nude mice in vivo. These effects are coincident with changes in the cellular levels of IAP family members such as c-IAP1, detected by Western analysis. These data are consistent with previously described autoubiquitination and subsequent proteasomal degradation of c-IAP1 following IAP antagonism. We have developed a high-throughput, quantifiable and sensitive assay to measure c-IAP1 levels in multiple cell lines, xenografts and in PBMCs using the MesoScale Discovery (MSD) Platform. The c-IAP1 MSD assay has a lower limit of quantification of 1.6 ng/ml of cell lysate, has precision of &amp;lt;10% CV and is linear down to at least a 4-fold dilution of lysate. Quantifiable changes in cellular c-IAP1 protein may serve as an ideal proximal pharmacodynamic (PD) biomarker to measure IAP family inhibition and degradation in the cell, particularly in the evaluation of candidate inhibitors targeting the IAP pathway in the clinical setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4409. doi:10.1158/1538-7445.AM2011-4409
SHORT AND LONG TERM OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTION VERSUS CORONARY ARTERY BYPASS GRAFTING IN OLDER (&gt;70 YEARS) PATIENTS WITH UNPROTECTED LEFT MAIN CORONARY ARTERY DISEASE IN THE ERA OF DRUG ELUTING STENTS
Authors: Mahin Khan, Waleed Kayani, Razvan Dadu, Salim Virani, Ihab Hamzeh, Hani Jneid, Mahboob Alam, Mostafa El-Refai, Nasser Lakkis
Journal: Journal of the American College of Cardiology (2016)
Mechanisms of Wound Healing
Authors: Edwin D. Savlov, J. Englebert Dunphy
Journal: New England Journal of Medicine (1954)

THE presence of a factor promoting the rehealing of wounds has been postulated for many years. The excellent healing of the resutured dehiscence has often been noted clinically.1 However, evidence of the nature of the factor or factors responsible for this effect has been lacking.A systemic healing-promoting factor was proposed by Sandblom2 as being responsible for the increased rate of healing that he found in wounds made after a given time at a distance from a primary wound. The greatest effect seemed to be present during the second week after wounding. This concept has been disputed by Taffel, Donovan . . .
Diagnostic yield of endoscopic ultrasonography (EUS), EUS-guided fine-needle aspiration (EUS-FNA), cyst fluid tumour markers &amp; cytology in pancreatic cystic neoplasms
Authors: R Repak, S Rejchrt, J Bartova, E Malirova, V Tycova, J Bures
Journal: Endoscopy (2006)

Background: Cystic neoplasms of the pancreas represent a heterogeneous group of tumours with varied malignant potential.
P4-19-03: Physical and Psychological Sequelae of Breast Cancer in Men.
Authors: KJ Ruddy, A Giobbie-Hurder, SH Giordano, S Goldfarb, S Kereakoglow, EP Winer, AH Partridge
Journal: Cancer Research (2011)

Abstract Introduction: Little is known about the physical and emotional health of men with breast cancer. Information is also lacking regarding whether their informational and supportive care needs are being met regarding fertility and genetic concerns. Methods: In an online pilot study recruiting participants through three websites focused on male breast cancer, www.outoftheshadowofpink.com, www.malebreastcancer.org, and www.malebreastcancer.ca, we surveyed men with breast cancer about their attitudes, symptoms, experiences, and health perceptions. We measured anxiety and depression using the Hospitalized Anxiety and Depression Scale (HADS), health-related quality of life (QOL) using Functional Assessment of Cancer Therapy-Breast (FACT-B), and hormonal and sexual symptoms using the Expanded Prostate Cancer Index Composite (EPIC) Hormonal and Sexual Scales. We assessed select toxicities from therapy and history of genetic and fertility counseling. Results: Forty-two men responded to this online survey at least in part. Conclusions: Men with breast cancer experience substantial symptoms in follow-up. Sexual functioning, in particular, may be impaired (in men without cancer, mean EPIC Sexual Score is 61.4 with SD 23.6). Hormonal symptoms are also prevalent (in men without cancer, mean EPIC Hormonal Score is 91.7 with SD 9.7). We plan to use data from this pilot study to inform a larger study and develop targeted interventions to improve sexual functioning and reduce symptoms in male breast cancer survivors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-19-03.
Abstract 2064: Down-regulation of miR-31 is associated with metastatic potential of human and canine osteosarcoma
Authors: Tamene Melkamu, Daniel F. Carlson, James P. Farese, Fekadu Kassie
Journal: Cancer Research (2010)

Abstract Osteosarcoma is the most common primary bone tumor in humans and dogs. The primary cause for the poor survival of patients with osteosarcoma in both species is the emergence of metastases in organs distant from the primary tumor, especially in the lung. Therefore, identification of molecular determinants of osteosarcoma metastasis is highly warranted. In order to identify microRNAs (miRNAs) that regulate osteosarcoma metastasis, we examined, using qRT-PCR, levels of 10 miRNAs commonly associated with cancer metastasis (miR-10b, miR-146a, miR182, miR183, miR-206, miR-335, miR373, miR-520c-5p, miR-21 and miR-31) in total RNA samples prepared from canine parental osteosarcoma (POS) and highly metastatic POS (HMPOS) cells. Of the 10 miRNAs, only miR-31 showed differential expression between the two cell lines (reduced by 7.8-fold in HMPOS cells versus POS cells). Exposure of HMPOS cells to various chemopreventive agents (myo-inositol, indole-3-carbinol, diindolylmethane, deguelin, phenethyl isothiocyanate, cisplatin, and aza-2′-deoxycytidine) increased the level of miR-31 at least by two-fold, the most potent agents being deguelin and phenethyl isothiocyanate. Subsequently, we assessed the expression of miR-31 in additional canine osteosarcoma cell lines (three cell lines established from primary tumors and three cell lines developed from pulmonary metastases) and human osteosarcoma cell lines differing in metastatic potential (parental SaOS2, low- (LM2), and high- (LM7) metastatic cells). miR-31 levels decreased by 18-fold in canine cell lines derived from pulmonary metastatic tumors relative to that obtained from primary tumors and by 2-fold and 3-fold in LM2 and LM7 cells, respectively, compared to the expression in parental Saos-2 cells. Also, analysis of 3 primary human osteosarcoma tissues and 3 pulmonary metastatic tissues revealed a 13-fold reduction of miR-31 in metastatic tissues relative to primary tumor tissues. In preliminary experiments where attempts were made to identify potential targets of miR-31, exogenous over-expression of a synthetic miR-31 cassette in HMPOS cells negatively regulated a tight junction protein claudin-2, which is incriminated in cancer metastasis. In summary, our studies indicate that miR-31 is a promising marker for the metastatic potential of osteosarcoma and for disease prognosis. Moreover, reactivation of silenced miR-31 by chemopreventive/chemotherapeutic agents could reverse osteosarcoma metastasis. 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 2064.
Abstract SY10-01: Uncovering the cellular origin of skin cancers
Authors: Cedric Blanpain
Journal: Cancer Research (2012)

Abstract Stem cells (SCs) are responsible for tissue homeostasis and repair. SCs have been hypothesized to be the cells at the origin of cancer. However, for the vast majority of cancers, the cell at the origin of tumor initiation is still unknown. Two epithelial skin cancers are frequent in human populations: the basal cell carcinoma (BCC) and the squamous cell carcinoma (SCC). We developed new genetic approaches to identify the cells at the origin of BCC and SCC in mice. Using mice conditionally expressing constitutively active Smoothened mutant (SmoM2) or KRas mutant (G12D), we activated hedgehog or Ras signaling in different cellular compartments of the skin epidermis, and determined from which epidermal compartments oncogene expression induces cancer formation. Using clonal analysis, we found that SmoM2 induced BCC arise from long-term resident progenitor cells of the interfollicular epidermis. In contrast, expression of mutant KRas in hair follicle bulge stem cells (SCs), but not in their transient amplifying progeny, led to benign squamous skin tumor (papilloma). Whereas no malignant tumor was observed following KRasG12D expression alone, expression of KRasG12D combined with the loss of p53 induced invasive SCC formation (3). Our studies uncover the cells at the origin of SmoM2 induced BCC and and Kras induced SCC in mice and demonstrate that expression of differentiation markers in tumor cells is not necessary predictive of the cancer initiating cells. We have now developed novel strategy to isolate by flow cytometry oncogene targeted cells at different time following oncogene expression and determined the molecular changes associated with tumor initiation and malignant progression. The functional relevance of these genes is currently investigated using gain and loss of function in mice. These new results and the relevance of these findings to human skin cancers will be presented. Acknowledgement This work is supported by Welbio, the FNRS, the program d'excellence CIBLES of the Wallonia Region, Fondation Contre le Cancer, the European Research Council (ERC) and the EMBO Young Investigator Program. 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 SY10-01. doi:1538-7445.AM2012-SY10-01
Abstract 338: Enhanced cetuximab and radiosensitization with src inhibition in head and neck cancer
Authors: Chunrong Li, Mari Iida, Emily Dunn, Deric L. Wheeler
Journal: Cancer Research (2010)

Abstract The epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase (RTK) that initiates a spectrum of signaling pathways that promote cell proliferation, differentiation, migration, motility, and metastasis. The EGFR has been strongly linked to the etiology of head and neck squamous cell carcinoma (HNSCC). The first major phase III clinical trial combining cetuximab with radiation in HNSCC confirmed a strong survival advantage for patients on the cetuximab arm. It has recently been reported, however, that cetuximab and radiation can induce EGFR to the nucleus where it can enhance resistance to both of these therapeutic modalities. In this report we sought to determine how to block cetuximab and radiation induced translocation of EGFR to the nucleus to increase the efficacy of this therapeutic regimen in HNSCC. We utilized three established HNSCC lines, SCC1, SCC6 and SCC1483 and measured nuclear translocation of the EGFR after treatment with cetuximab, radiation or the combination. Both cetuximab and radiation treatment could induce nuclear translocation of the EGFR in all SCC lines tested. Strikingly, time course analysis indicated that cetuximab could stimulate movement of the EGFR to the nucleus within one hour where it maintained its present for greater than 96 hours. Conversely, radiation could stimulate EGFR translocation to the nucleus within 0.5 hours, but returned to baseline levels within four hours. Both cetuximab and radiation treatment of SCC lines led to the phosphorylation of tyrosine 845 (Y845) of the EGFR. Y845 is phosphorylated specifically by the non-receptor tyrosine kinase Src and/or its family of kinases (SFKs). Blockade of SFKs by dasatinib could abrogate cetuximab and radiation induced EGFR translocation to the nucleus indicating that SFKs are crucial for the movement of the EGFR to the nucleus. In addition, pre-treatment of HNSCC cells with dasatinib, followed by cetuximab and radiation enhanced the suppression of ERK activity in all three SCC cell lines. Furthermore, combining dasatinib with cetuximab/radiation treatment exhibited additive inhibitory effects on cell growth or clonogenic formation. These data suggest that both cetuximab and radiation can induce EGFR to the nucleus and blockade of SFKs using dasatinib can abrogate this translocation. Collectively these findings may suggest that dasatinib can limit EGFR translocation to the nucleus and may enhance radiotherapy plus cetuximab in HNSCC. 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 338.
Case 12-2012
Authors: Kenneth C. Sassower, Lauren M. Allister, Sjirk J. Westra
Journal: New England Journal of Medicine (2012)

A 10-month-old girl was seen in the emergency department because of vomiting and episodes of unresponsiveness, which had begun suddenly 7 hours earlier. She gradually became somnolent. Vital signs, a physical examination, and brain imaging were normal.
P232 Treatment Of Allergic Rhinitis With Theophylline : A Double-blind, Randomised, Crossover Study
Authors: P. Sankaran, C. Brockwell, A. Clark, A. Wilson
Journal: Thorax (2014)

<h3>Background</h3> Allergic rhinitis and Asthma are considered as ‘one airway disease’. Theophylline has been used as a bronchodilator in asthma for decades but more recently its anti-inflammatory properties have been identified. We hypothesise that treatment with low dose theophylline in patients with persistent allergic rhinitis is likely to improve the total nasal symptom scores and there by demonstrate a clinically meaningful difference. <h3>Methods</h3> This was a single centre double- blind, randomised, placebo-controlled cross-over study of the effects of theophylline (one capsule of Theophylline 200 mgs as Uniphyllin continus twice a day for 4 weeks) in 21 patients with persistent allergic rhinitis in Norwich, U. K. Reference: NCT0113278. Primary outcome was Total Nasal Symptom Score (TNSS) after each intervention period. Secondary endpoint measures were differences in the domiciliary average total nasal symptom score, differences in nasal peak inspiratory flow (PNIF), differences in domiciliary nasal peak inspiratory flow and difference in Sino-Nasal Outcome Test (SNOT)-22. <h3>Results</h3> Primary Endpoint There was no significant (p = 0.276) difference in Total Nasal Symptoms scores during Theophylline treatment period and placebo period, mean (SD) (Table). The intention-to-treat analysis results were in keeping with the per protocol analysis. Secondary End points PNIF in the Theophylline period was 112.38(±43.49) compared to the placebo period 122.86(±53.77), p = 0.171 (Table). There was no change in SNOT-22 (p = 0.867) between treatment periods but there was a non-significant improvement with Theophylline (39.00 ± 19.78) compared to placebo (38.00 ± 19.63) treatment period. There was a non-significant improvement in the domiciliary total nasal symptom scores (TNSS) between Theophylline (3.53 ± 2.35) and placebo (2.81 ± 2.46). Nasal scrape samples were stained with HDAC2 antibodies and the signals were very week. <h3>Conclusion</h3> This is the first study evaluating Theophylline in persistent rhinitis. Low-dose Theophylline had no significant effects on Total nasal Symptom scores; Rhinosinusitis symptoms and nasal patency assessed using peak nasal inspiratory flow. There was a non-significant improvement in the total nasal symptom scores and sino-nasal outcome test and domiciliary nasal scores.