tbuckley/cabot-search huggingface dataset:
Assessment of concomitant versus sequential aromatase inhibitor with radiotherapy for postmenopausal women with early-stage breast cancer.
Authors: N. M. Abd El-Bary, T. Hashem
Journal: Journal of Clinical Oncology (2010)

667 Background: Combined radiation and hormone therapies have become common clinical practice in recent years for locally advanced prostate cancer. The use of such concomitant therapy in the treatment of breast disease has been infrequently reported in literature with few available published studies confirm the superiority of association of radiation with tamoxifen as opposed to radiation therapy alone in decreasing local recurrences. Toxicity associated with such concomitant therapy includes mainly subcutaneous and pulmonary fibroses. To our knowledge, no studies were done to address the outcome of association of radiotherapy and aromatase inhibitors. Methods: This is a prospective randomized trial on forty postmenopausal women with early stage breast cancer who proved to be hormone sensitive. Those patients were randomized into two groups: group I: patients received aromatase inhibitor anastrazole 1 mg daily after the last cycle of adjuvant chemotherapy and continue it during as well as after the end of radiotherapy for 3 years (or disease progression). Group II: patients received anastrazole three weeks after the end of radiotherapy. Toxicity profile and 3 year DFS were assessed. Results: Early radiation reactions in the form of grade III skin reactions were observed in 3 (15%) patients in group I and in 2 (10%) patients in group II (p > 0.05). Late radiation reactions in the form of grade II radiation pneumonitis or lung fibrosis were detected in 3 (15%) patients in group I and 2 (10%) patients in group II (p > 0.05). Local recurrence was observed in one patient in group II during the third year of follow up, no local recurrence was seen in group I (p > 0.05). Distant metastasis was detected in 5 (25%) patients in group I and in 6 (30%) patients in group 2 (p > 0.05). Conclusions: Starting aromatase inhibitors during radiotherapy appears to be safe and at least equally effective as its use after the end of radiotherapy. Although there was a trend toward better local control in the concurrent group, yet it did not reach a statistically significant value. Large number of patients and longer follow-up periods are recommended. No significant financial relationships to disclose.
Colonic duplication in adulthood presenting with diarrhea
Authors: Ozge Caklili, İlyas Tuncer, Yasar Colak, Duygu Kosemetin, Ayşe Ceyran
Journal: Endoscopy (2013)

In pediatric clinics, alimentary tract duplications are seen with an incidence of approximately 1 in 4500 [1]. Most cases are diagnosed within the first 5 years of life [2]. The condition is seen infrequently in adults. Patients usually present with constipation, diarrhea, abdominal pain, abdominal mass, and, sometimes, acute abdomen, volvulus, or perforation [3]. There are two types of colonic duplication: tubular and cystic. Diagnosis requires a careful history and detailed imaging with endoscopy, computed tomography, and in some cases barium meal study. Correct diagnosis is important not only because the symptoms decrease patients' quality of life, but also because with time patients are at increased risk of developing carcinoma [4]. The most common form of carcinoma associated with alimentary tract duplication is adenocarcinoma.
AB0044 Analysis of recombinant monoclonal antibodies from single B cells reveals early defects of B cell tolerance checkpoints in patients with sjÖgren’s syndrome
Authors: E. Corsiero, N. Sutcliffe, H. Wardemann, C. Pitzalis, M. Bombardieri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Sjögren's syndrome (SS) is an autoimmune disease characterized by high affinity circulating autoantibodies and characteristic B cell disturbances with a predominance of naïve and a reduction of memory B cells in the periphery. It is unknown at what stages of B cell differentiation tolerance checkpoints are defective in SS. <h3>Objectives</h3> Here we aimed to determine the frequency of self-reactive and polyreactive B cells in the circulating naïve compartment of SS patients. <h3>Methods</h3> Single IgD+CD27- naïve (and CD27+ memory) B cells were FACS sorted from 7 SS patients and RNA used to amplify Ig VH and VL genes which were then cloned and expressed as recombinant monoclonal antibodies displaying an identical specificity of the original B cells. B cells from healthy donors (HD) were used as control. Recombinant antibodies were tested towards different autoantigens to determine the frequency of autoreactive and polyreactive clones. <h3>Results</h3> A total of 80 individual recombinant antibodies were generated from naïve and memory B cells of SS patients. Analysis of the VH and VL gene usage showed no significant differences between SS and HD. Preliminary data showed ANA reactivity but not polyreactivity in several peripheral naïve B cells from SS patients, suggesting an accumulation of autoreactive naive B cells in the periphery. <h3>Conclusions</h3> Here using a novel strategy to express recombinant antibodies from single B cells we demonstrated an elevated frequency of autoreactive naïve B cells in the circulation of SS patients. This evidence likely reflects early defects in B cell tolerance checkpoints. <h3>References</h3> Menard L, Samuels J, Ng YS, Meffre E. Inflammation-independent defective early B cell tolerance checkpoints in rheumatoid arthritis. Arthritis Rheum 2011;63:1237-1245. Tiller T, Meffre E, Yurasov S, Tsuiji M, Nussenzweig MC, Wardemann H. Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning. J Immunol Methods 2008;329:112-124. Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC. Predominant autoantibody production by early human B cell precursors. Science 2003;301:1374-1377. <h3>Disclosure of Interest</h3> None Declared
Case 37-2007
Authors: Marc J. Semigran, Lynne Warner Stevenson, Jonathan J. Passeri, James R. Stone
Journal: New England Journal of Medicine (2007)

A man was admitted 1 month after heart transplantation because of left ventricular dysfunction. Systemic amyloidosis with cardiomyopathy had been diagnosed 19 months earlier; cardiac function declined rapidly, and he underwent sequential cardiac and bone marrow transplantation. His cardiac function was then normal, and biopsy specimens showed no rejection. When an echocardiogram showed left ventricular dysfunction, a diagnostic procedure was performed.
Methotrexate Therapy and Liver Disease
Authors: Jean-François J. Dufour, Marshall M. Kaplan
Journal: New England Journal of Medicine (1996)

To the Editor: Methotrexate is effective in the treatment of a number of chronic diseases, such as Crohn's disease,1 but concern about long-term hepatotoxicity has limited its widespread use. Although elevated serum aminotransferase concentrations are often considered a reason for stopping methotrexate,1 there is little information about the nature or seriousness of the elevations and little, if any, correlation between them and liver histology. We report on a patient who had transient increases in serum aminotransferase values with unchanged liver histology while receiving methotrexate for primary sclerosing cholangitis. A 37-year-old man was referred to our center because of jaundice and . . .
SP0181 Detrimental effects of interferon alpha on angiogenesis
Authors: M.J. Kaplan
Journal: Annals of the Rheumatic Diseases (2013)

Patients with systemic lupus erythematosus (SLE) have up to a 50-fold increased risk of developing atherosclerotic cardiovascular disease. Traditional CV risk factors seem to be less important predictors of CV events than the presence of active SLE. Indeed, immune dysregulation characteristic of lupus appears to play the dominant role in atherogenesis. While both SLE-specific and non-specific mechanisms have been proposed to play a prominent role in the induction of premature vascular damage in this disease, the exact etiology remains unclear. We have proposed that an imbalance between vascular damage and repair likely induced by Interferon-α and other type I Interferons could play a prominent role in the induction of accelerated atherosclerosis in SLE. Our group and others have recently elucidated the potential role that these cytokines play in the development and progression of premature atherosclerotic disease in SLE and, potentially, in other autoimmune diseases. We have recently described some of the pathways by which IFN-alpha has deleterious effects on angiogenesis in endothelial progenitor cells and circulating angiogenic cells. Strong evidence pointing to a deleterious role of type I IFNs in aberrant vasculogenesis and atherothrombosis has recently been described by our group. More recently, a novel role for aberrant neutrophils in the development of vascular damage and abnormal vascular repair in SLE has emerged. The recent description of a distinct subset of proinflammatory neutrophils isolated from lupus patients which induces vascular damage and synthesizes type I Interferons has shed new light into a potentially important cell subset implicated in endothelial damage. <h3>Disclosure of Interest</h3> None Declared
FRI0459 Impact of ergometric test in patients with rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematosus, without cardiovascular symptoms, before starting a supervised physical activity program:
Authors: F. Jennings, E.T. Reis Neto, U.S. Siqueira, V.L. Szejnfeld, J. Natour, E.I. Sato, M.M. Pinheiro
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Cardiovascular (CV) diseases are the most relevant causes of mortality in patients with autoimmune rheumatic diseases (AIRD), including rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE). Supervised physical exercise (SPE) is an important non-pharmacological strategy for clinical management of these patients, particularly on aspects related to metabolic syndrome and other concomitant diseases. <h3>Objectives</h3> To evaluate the impact of a simple ergometric test (ET) in patients with AIRD, without cardiovascular symptoms, before starting a SPE. <h3>Methods</h3> A total of 264 ET from sedentary 133 RA, 84 AS and 47 SLE patients were analyzed. The patients underwent ET before starting a SPE program in order to be included in 3 randomized clinical trials. Patients with CV symptoms, previous CV events, uncontrolled hypertension, severe disease activity or taking high doses of glucocorticosteroids and older than 60 years were excluded. All outcomes occurring after cardiac evaluation were examined to evaluate the impact of each one on the final clinical decision. <h3>Results</h3> From 264 baseline ET, 34 (12.9%) were considered positive. These patients were not included in the controlled and randomized SPE and a cardiologic evaluation was recommended. The main peculiarities of these patients as well as the outcomes can be seen in Table 1. After cardiologic evaluation, the most of them were considered clinically relevant, since there were changes in diagnosis and therapeutic management, including invasive procedures (cardiac catheterization) and specific medications. If the ET had not been performed, these patients have been missed and would be at CV risk. <h3>Conclusions</h3> Positive ET is frequent in asymptomatic patients with AIRD, particularly in RA patients. In addition, these CV abnormalities had serious clinical implications, such as systemic and pulmonary hypertension, arrhythmia and ischemic heart disease. Our data suggest that asymptomatic and sedentary patients with RA, AS and SLE should be evaluated for CV diseases before starting moderate to vigorous exercise programs. <h3>References</h3> Garber CE, Blissmer B, Deschenes MR et al. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Med Sci Sports Exerc. 2011; 43 (7): 1334-59. Kamioka H, Tsutani K, Okuizumi H et al. Effectiveness of aquatic exercise and balneotherapy: a summary of systematic reviews based on randomized controlled trials of water immersion therapies. J Epidemiol. 2010; 20 (1): 2-12. <h3>Disclosure of Interest</h3> None Declared
MYOCARDIAL UPTAKE OF THALLIUM 201 IS INCREASED DURING ATRIAL PACING WHEN COMPARED TO EXERCISE TESTING.
Authors: Georges Y. Baillet, Pierre B. Lambert, Ray Matthews, Paul A. Macias, Arnulfo S. Pleyto, Ismael G. Mena
Journal: Clinical Nuclear Medicine (1987)

Baillet, Georges Y.; Lambert, Pierre B.; Matthews, Ray; Macias, Paul A.; Pleyto, Arnulfo S.; Mena, Ismael G. Author Information
Low Power and Striking Results — A Surprise but Not a Paradox
Authors: Alexander M. Walker
Journal: New England Journal of Medicine (1995)

In this issue of the Journal, Verdonck et al.1 report on a study that, as they planned it, was barely large enough to detect a massive advantage for a controversial and expensive therapy. Moreover, the way they calculated the size of their sample was too forgiving: it presupposed a one-sided test of significance, which ordinarily would not be acceptable in these pages. Yet the study does appear here, and it provides evidence strong enough to guide therapeutic decisions. What went right?Verdonck et al. studied patients with non-Hodgkin's lymphoma who had partial responses to three cycles of CHOP therapy (cyclophosphamide, . . .
Ferritin: Structure, Synthesis and Function
Authors: Robert R. Crichton
Journal: New England Journal of Medicine (1971)

StructureOF all the indispensable trace elements required by higher animals iron is by far the most important on account of its presence as a structural component of hemoglobin. Although about 70 per cent of the total iron of the human body is present as hemoglobin, and about 3 per cent in the muscles as myoglobin, most of the remainder is found in ferritin, which, together with hemosiderin, is the major storage form of iron. Ferritin was first isolated and crystallized by Laufberger in 1937 from the spleen and liver of the horse.1 Ferritin is known to occur in a . . .
A3.33 Increased rho-kinase activity in temporal artery biopsies from patients with giant cell arteritis
Authors: Lindsay Lally, Navneet Narula, Alessandra B Pernis, Wei-Ti Huang, Uzunma Udeh, Robert F Spiera
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background/Purpose</h3> ROCKs are implicated in the pathogenesis of many vascular diseases. ROCK activation is associated with Th17 differentiation and production of Th17-associated cytokines, IL-17 and IL-21. Th17 cells and related cytokines are present in increased levels in active Giant Cell Arteritis (GCA). ROCK activity in GCA is unknown. The aim of this study was to assess ROCK activity in temporal artery biopsy (TAB) specimens in GCA versus controls. <h3>Methods</h3> All TAB performed at a tertiary care center over a 5 year period were identified. Charts were reviewed for clinical information. Subjects were categorised according to 1990 ACR criteria and TAB status into 3 groups: GCA with positive TAB, GCA with negative TAB and age-sex-matched controls. Paraffin-embedded temporal artery specimens were stained for Phospho-Ezrin/Radixin/Moesin (pERM), a surrogate of ROCK activity, using immunohistochemical stain. pERM stained slides were reviewed by a pathologist blinded to clinical status. Three separate areas (endothelium, adventitia and vaso vasorum) were scored for intensity of staining on a scale of 0-2 for total possible composite score of 6. Primary outcome was biopsy pERM intensity score in subjects with GCA compared to controls. <h3>Results</h3> Nineteen subjects with GCA had positive TAB, 17 subjects had GCA with negative TAB and18 age-sex-matched controls were analysed. Mean age was 77.9 ± 9.1years and 81.4% were female with no differences in baseline demographics between the 3 groups. Compared to controls, GCA subjects with either positive or negative TAB had significantly higher pERM intensity scores (p = 0.0159). Adjusting for diabetes, hypertension, prednisone, and statin use, GCA subjects still had higher pERM intensity scores (OR 7.3; 95% CI 1.9–25.9, p = 0.0046). Comparing GCA with negative TAB to controls, high pERM score had sensitivity of 90.4% and negative predictive value of 90.9%. <h3>Conclusion</h3> Subjects with GCA had more intense pERM staining in TAB specimens compared to age- sex-matched controls regardless of whether TAB was positive or negative, suggesting increased ROCK activity in GCA. High pERM staining score had a sensitivity higher than the sensitivity of routine TAB histopathology itself, suggesting it may be a useful adjunctive diagnostic tool in patients with negative TAB. The ROCK pathway warrants further investigation in GCA as it may be of both diagnostic and therapeutic significance.
Abstract 4926: Loss of ZBRK1 contributes to the increase of KAP1 and promotes KAP1-mediated metastasis and invasion in cervical cancer.
Authors: Wei-Jan Wang, Li-Fang Lin, Chien-Feng Li, Wen-Ming Yang, Dennis Ding-Hwa Wang, Wen-Chang Chang, Wen-Hwa Lee, Ju-Ming Wang, Ju-Ming Wang
Journal: Cancer Research (2013)

Abstract ZBRK1, a zinc finger protein that interacts with breast cancer 1 (BRCA1) and KRAB-ZFP-associated protein 1 (KAP1), has been suggested to serve as a tumor suppressor via repression of tumor metastasis/invasion. To date, the detailed molecular mechanisms for how BRCA1 and KAP1 participate in ZBRK1-mediated transcriptional repression, metastasis and invasion as well as the associated clinical relevance remain unclear. In this study, we demonstrated that both the N- and C-terminal domains of ZBRK1 are important for inhibiting cell proliferation and anchorage-independent growth in cervical cancer. Specifically, the N-terminal KRAB domain of ZBRK1 displayed a more crucial role in inhibiting metastasis and invasion through modulation of KAP1 function in a transcriptionally dependent manner. The loss of ZBRK1 results in an increase of KAP1 expression, which enhanced migration and invasion of cervical cancer cells both the in vitro and in vivo. Moreover, an inverse correlation of expression levels was observed between ZBRK1 and KAP1 following tumor progression from in situ carcinoma to invasive/metastatic cervical cancer specimens. Taken together, the current results indicate that a loss of ZBRK1 contributes to the increased expression of KAP1, potentiating its role to enhance metastasis and invasion. Citation Format: Wei-Jan Wang, Li-Fang Lin, Chien-Feng Li, Wen-Ming Yang, Dennis Ding-Hwa Wang, Wen-Chang Chang, Wen-Hwa Lee, Ju-Ming Wang, Ju-Ming Wang. Loss of ZBRK1 contributes to the increase of KAP1 and promotes KAP1-mediated metastasis and invasion in cervical cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4926. doi:10.1158/1538-7445.AM2013-4926
Recurrent Hyperfunctioning Parathyroid Gland Demonstrated on Radionuclide Imaging and an Intraoperative Gamma Probe
Authors: G U Hung, H S Wu, S C Tsai, C H Kao, W Y Lin, J H Lin, S J Wang
Journal: Clinical Nuclear Medicine (2000)

Radionuclide imaging with Tc-99m MIBI is the preferred mode of parathyroid localization in current practice. It also successfully identifies hyperfunctioning autotransplanted parathyroid tissue. The authors report a case with recurrent hyperparathyroidism after total parathyroidectomy and autotransplantation in the forearm. Double-phase Tc-99m MIBI imaging successfully localized the hyperfunctioning parathyroid tissue, which was missed by magnetic resonance imaging and ultrasonography. In addition, the parathyroid tissue was localized using an intraoperative probe at subsequent surgery.
Heightened Interaction between Platelets and Factor VIII/von Willebrand Factor in a New Subtype of von Willebrand's Disease
Authors: Zaverio M. Ruggeri, Franco I. Pareti, Pier Mannuccio Mannucci, Nicola Ciavarella, Theodore S. Zimmerman
Journal: New England Journal of Medicine (1980)

The form of von Willebrand's disease characterized by a qualitative abnormality of Factor VIII/von Willebrand factor (FVIII/vWF) in plasma has been designated as Type II. We have now identified 20 persons from five families whose qualitatively abnormal FVIII/vWF shows heightened responsiveness to ristocetin. We have classified this form of the disease as Type IIB and reclassified as Type IIA the form previously described as Type II, in which the interaction of the abnormal FVIII/vWF with platelets is decreased or absent in the presence of ristocetin. The enhanced reactivity of FVIII/vWF in Type IIB was evident in studies of ristocetin-induced platelet agglutination and of binding of FVIII/vWF to platelets in the presence of ristocetin. In both Type IIA and IIB, crossed immunoelectrophoresis of plasma FVIII/vWF demonstrated similar absence of the larger, less anodic forms. These findings suggest that ristocetin-mediated interactions between platelets and FVIII/vWF do not accurately reflect the "bleeding-time" (von Willebrand factor) defect in this newly described subtype of von Willebrand's disease.
Abstract 1988: Increased expression of eukaryotic protein synthesis initiation factor eIF4G by the daidzein metabolite equol may contribute to breast cancer malignancy
Authors: Columba de la Parra, Elisa Otero-Franqui, Suranganie Dharmawardhane
Journal: Cancer Research (2012)

Abstract The role of dietary soy in cancer has been the subject of intense investigation and is thought to be cancer preventive. However, the beneficial effects of soy on established breast cancer is controversial. We recently demonstrated that dietary daidzein and combined soy isoflavones (genistein, daidzein, and glycitein) promoted breast cancer progression in a nude mouse model by increasing both primary mammary tumor growth and metastasis. Dietary daidzein significantly upregulated cancer promoting molecules including eukaryotic protein synthesis initiation factors (eIF) eIF4G and eIF4E. Herein, using tumors from mice treated orally with daidzein, we show that increased eIF expression is associated with expression of mRNAs with long structured 5′ untranslated regions and internal ribosomal entry sites (IRES) that are sensitive to eIF4E and eIF4G levels. We then tested the hypothesis that daidzein upregulates protein synthesis initiation in breast cancer, but found that daidzein treatment did not affect the levels of eIFs in the same MDA-MB-435 cell line in vitro. Therefore, we tested the effect of equol that is metabolized from daidzein by the gut bacteria in mice and humans. Results show that equol specifically upregulated eIF4G, but not eIF4E, in MDA-MB-435 and MDA-MB-231 human breast cancer cells. Equol treatment also increased gene and protein expression of c-MYC and protein expression of other cell survival and proliferation promoting molecules with IRES sites. The elevated eIF4G in response to equol was not associated with eIF4E in a cap binding co-capture assay. Therefore, upregulation of eIF4G by equol may regulate cap-independent protein synthesis initiation resulting in cancer cell survival, proliferation, and thus, tumor progression. This research was supported by grant numbers US Army/BCRP W81XWH-11-1-0199 to CD, to NIH/NIGMS SC3GM084824 to SD 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 1988. doi:1538-7445.AM2012-1988