tbuckley/cabot-search huggingface dataset:
Prospective survey of investigations in outpatients referred with iron deficiency anaemia.
Authors: A S McIntyre, R G Long
Journal: Gut (1993)

Recent evidence has suggested that colonic neoplasm may be missed in patients presenting with iron deficiency anaemia unless colonic investigations are performed on all patients even when an alternative cause has been found. This study prospectively surveyed 114 consecutive patients referred from family practitioners to an outpatient clinic for the investigation of iron deficiency anaemia to determine the diagnoses contributing to the anaemia, the usefulness of certain clinical features, and the role of colonic and other investigations in obtaining the diagnosis. Upper gastrointestinal lesions contributing to anaemia were identified in 45 patients while colonic lesions were found in 18. Twenty three patients had a non-gastrointestinal cause for anaemia and in 12 patients no cause was found. Only two patients were identified as having colonic neoplasia (a small adenomatous polyp in each case) coexisting with upper gastrointestinal lesions. Symptoms and signs had a sensitivity and specificity of upper gastrointestinal disease of 50% and 83% respectively, and 44% and 80% for colonic disease. Endoscopy had a high yield (42%) and duodenal biopsy identified coeliac disease in three patients (two were aged > 70 years) each of whom had normal folate values. Barium enema had a yield of 13%. All colonic carcinomas occurred in patients > 65 years. The coexistence of colonic cancer or large polyps with an upper gastrointestinal lesion identified at endoscopy was rare in outpatients referred from family practitioners. Clinical symptoms and signs were poor indicators of the investigations that will detect a cause for the anaemia. Endoscopy (with duodenal biopsy) should be performed on all patients. The yield from barium enema is so low in young patients that if an upper gastrointestinal cause is found and there are no clinical indicators it would seem unnecessary.
The Rebound Phenomenon-Fact or Fancy?
Authors: ROBERT VAN CLEVE
Journal: Circulation (1965)

Long-term anticoagulant therapy (coumadin) was gradually tapered over a 6-week period in 63 patients, and stopped abruptly in 71. All of these patients had been on coumadin following myocardial infarction. A careful follow-up showed that there was no difference in the incidence of thrombotic events in the first 6 weeks after discontinuation of therapy, whether this was stopped abruptly or gradually. These results suggest that clinically recognized "rebound" thrombosis does not occur after long-term coumadin therapy is stopped. There appears to be no hazard inherent in stopping long-term coumadin therapy abruptly. A possible exception to this is patients whose therapy must be stopped because of bleeding episodes.
Microscopic Intratumoral Dosimetry of Radiolabeled Antibodies Is a Critical Determinant of Successful Radioimmunotherapy in B-Cell Lymphoma
Authors: Yong Du, Jamie Honeychurch, Martin Glennie, Peter Johnson, Tim Illidge
Journal: Cancer Research (2007)

Radioimmunotherapy is a highly effective treatment for some hematologic malignancies; however, the underlying mechanisms of tumor clearance remain poorly understood. We have previously shown that both targeted radiation using (131)I-labeled anti-MHC class II (MHCII) monoclonal antibody (mAb) plus mAb signaling with unlabeled anti-idiotype are required for the long-term clearance of tumor in syngeneic murine lymphoma models. In this study, we have investigated how the microdistribution of the targeted radiation component of this combination affects the long-term clearance of lymphoma. (131)I-labeled mAb targeting CD45 and MHCII antigens was found to deliver similar doses of radiation to tumor-bearing organ using conventional dosimetry ( approximately 1.0 Gy per MBq when (131)I was labeled to 500 mug mAb and given i.v. per mouse), but when used as radiation vectors in combination therapy only, (131)I-anti-MHCII plus anti-idiotype produced long-term survival. The profound differences in therapy did not seem to be dependent on levels of (131)I-mAb tumor-binding or antibody-dependent cytotoxicity. Instead, the microscopic intratumoral dosimetry seemed to be critical with the (131)I-anti-MHCII, delivering more concentrated and therefore substantially higher radiation dose to tumor cells. When the administered activity of (131)I-anti-CD45 was increased, a radiation dose response was shown in the presence of anti-idiotype and long-term survival was seen. We believe that these new insights should influence the selection of new antigen targets and the design of dosimetric methods in radioimmunotherapy of lymphoma.
Alterations of Left Ventricular Myocardial Characteristics Associated With Obesity
Authors: Chiew Y. Wong, Trisha O’Moore-Sullivan, Rodel Leano, Nuala Byrne, Elaine Beller, Thomas H. Marwick
Journal: Circulation (2004)

Obesity is associated with heart failure, but an effect of weight, independent of comorbidities, on cardiac structure and function is not well established. We sought whether body mass index (BMI) and insulin levels were associated with subclinical myocardial disturbances.Transthoracic echocardiography, myocardial Doppler-derived systolic (sm) and early diastolic velocity (em), strain and strain rate imaging and tissue characterization with cyclic variation (CVIB), and calibrated integrated backscatter (cIB) were obtained in 109 overweight or obese subjects and 33 referents (BMI <25 kg/m2). BMI correlated with left ventricular (LV) mass and wall thickness (P<0.001). Severely obese subjects (BMI >35) had reduced LV systolic and diastolic function and increased myocardial reflectivity compared with referents, evidenced by lower average long-axis strain, sm, cIB, lower CVIB, and reduced em, whereas LV ejection fraction remained normal. Differences in regional or global strain, sm, and em were identified between the severely obese (BMI >35) and the referent patients (P<0.001). Similar but lesser degrees of reduced function by sm, em, and basal septal strain and increased reflectivity by cIB were present in overweight (BMI, 25 to 29.9) and mildly obese (BMI, 30 to 35) groups (P<0.05). Although tissue Doppler measures were not associated with duration of obesity, they did correlate with fasting insulin levels and reduced exercise capacity. BMI was independently related to average LV strain (beta=0.40, P=0.02), sm (beta=-0.36, P=0.002), and em (beta=-0.41, P<0.001).Overweight subjects without overt heart disease have subclinical changes of LV structure and function even after adjustment for mean arterial pressure, age, gender, and LV mass.
Genomic Profiles Associated with Early Micrometastasis in Lung Cancer: Relevance of 4q Deletion
Authors: Michaela Wrage, Salla Ruosaari, Paul P. Eijk, Jussuf T. Kaifi, Jaakko Hollmén, Emre F. Yekebas, Jakob R. Izbicki, Ruud H. Brakenhoff, Thomas Streichert, Sabine Riethdorf, Markus Glatzel, Bauke Ylstra, Klaus Pantel, Harriet Wikman
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Bone marrow is a common homing organ for early disseminated tumor cells (DTC) and their presence can predict the subsequent occurrence of overt metastasis and survival in lung cancer. It is still unclear whether the shedding of DTC from the primary tumor is a random process or a selective release driven by a specific genomic pattern. Experimental Design: DTCs were identified in bone marrow from lung cancer patients by an immunocytochemical cytokeratin assay. Genomic aberrations and expression profiles of the respective primary tumors were assessed by microarrays and fluorescence in situ hybridization analyses. The most significant results were validated on an independent set of primary lung tumors and brain metastases. Results: Combination of DNA copy number profiles (array comparative genomic hybridization) with gene expression profiles identified five chromosomal regions differentiating bone marrow-negative from bone marrow-positive patients (4q12-q32, 10p12-p11, 10q21-q22, 17q21, and 20q11-q13). Copy number changes of 4q12-q32 were the most prominent finding, containing the highest number of differentially expressed genes irrespective of chromosomal size (P = 0.018). Fluorescence in situ hybridization analyses on further primary lung tumor samples confirmed the association between loss of 4q and bone marrow-positive status. In bone marrow-positive patients, 4q was frequently lost (37% versus 7%), whereas gains could be commonly found among bone marrow-negative patients (7% versus 17%). The same loss was also found to be common in brain metastases from both small and non-small cell lung cancer patients (39%). Conclusions: Thus, our data indicate, for the first time, that early hematogenous dissemination of tumor cells might be driven by a specific pattern of genomic changes.
Quadriceps wasting and physical inactivity in patients with COPD
Authors: Dinesh Shrikrishna, Mehul Patel, Rebecca J. Tanner, John M. Seymour, Bronwen A. Connolly, Zudin A. Puthucheary, Simon L.F. Walsh, Susannah A. Bloch, Paul S. Sidhu, Nicholas Hart, Paul R. Kemp, John Moxham, Michael I. Polkey, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2012)

Quadriceps weakness is an important complication of advanced chronic obstructive pulmonary disease (COPD) but few data exist concerning muscle bulk in early disease. We hypothesised that quadriceps bulk, measured by ultrasound rectus femoris cross-sectional area (USRF CSA ), would be reduced in mild, as well as advanced, COPD compared with controls, and would correlate with physical activity. 161 patients with stable COPD and 40 healthy subjects had a measurement of USRF CSA and wore a multisensor armband to record physical activity. USRF CSA was reduced in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I patients compared with healthy subjects (p=0.0002). Stage II–IV patients had reduced USRF CSA (p&lt;0.0001) compared with controls but were not significantly different from those with stage I disease. Physical activity level was reduced in stage I (p=0.002) and stage II–IV disease compared with controls. Using regression analysis, physical activity level was independently associated with USRF CSA in stage I (p=0.01) but not stage II–IV disease, where residual volume to total lung capacity ratio was the only independent predictor of physical activity level. Quadriceps wasting exists in patients with mild, as well as advanced, COPD, and is independently associated with physical inactivity in GOLD stage I disease. The identification of these patients may guide early lifestyle and therapeutic interventions.
Enhanced myogenic constriction of mesenteric artery in heart failure relates to decreased smooth muscle cell caveolae numbers and altered AT<sub>1</sub>‐ and epidermal growth factor‐receptor function
Authors: Ying Xu, Rob H. Henning, Maria Sandovici, Johannes J. van der Want, Wiek H. van Gilst, Hendrik Buikema
Journal: European Journal of Heart Failure (2009)
Prognostic Significance of Expression of a Single MicroRNA, <i>miR-181a</i>, in Cytogenetically Normal Acute Myeloid Leukemia: A Cancer and Leukemia Group B Study
Authors: Sebastian Schwind, Kati Maharry, Michael D. Radmacher, Krzysztof Mrózek, Kelsi B. Holland, Dean Margeson, Susan P. Whitman, Christopher Hickey, Heiko Becker, Klaus H. Metzeler, Peter Paschka, Claudia D. Baldus, Shujun Liu, Ramiro Garzon, Bayard L. Powell, Jonathan E. Kolitz, Andrew J. Carroll, Michael A. Caligiuri, Richard A. Larson, Guido Marcucci, Clara D. Bloomfield
Journal: Journal of Clinical Oncology (2010)

Purpose To evaluate the prognostic significance of expression levels of a single microRNA, miR-181a, in the context of established molecular markers in cytogenetically normal acute myeloid leukemia (CN-AML), and to gain insight into the leukemogenic role of miR-181a. Patients and Methods miR-181a expression was measured in pretreatment marrow using Ohio State University Comprehensive Cancer Center version 3.0 arrays in 187 younger (&lt; 60 years) adults with CN-AML. Presence of other molecular prognosticators was assessed centrally. A gene-expression profile associated with miR-181a expression was derived using microarrays and evaluated by Gene-Ontology analysis. Results Higher miR-181a expression associated with a higher complete remission (CR) rate (P = .04), longer overall survival (OS; P = .01) and a trend for longer disease-free survival (DFS; P = .09). The impact of miR-181a was most striking in poor molecular risk patients with FLT3-internal tandem duplication (FLT3-ITD) and/or NPM1 wild-type, where higher miR-181a expression associated with a higher CR rate (P = .009), and longer DFS (P &lt; .001) and OS (P &lt; .001). In multivariable analyses, higher miR-181a expression was significantly associated with better outcome, both in the whole patient cohort and in patients with FLT3-ITD and/or NPM1 wild-type. These results were also validated in an independent set of older (≥ 60 years) patients with CN-AML. A miR-181a-associated gene-expression profile was characterized by enrichment of genes usually involved in innate immunity. Conclusion To our knowledge, we provide the first evidence that the expression of a single microRNA, miR-181a, is associated with clinical outcome of patients with CN-AML and may refine their molecular risk classification. Targeted treatments that increase endogenous levels of miR-181a might represent novel therapeutic strategies.
The c-<i>MYC</i>NHE III<sub>1</sub>: Function and Regulation
Authors: Verónica González, Laurence H. Hurley
Journal: The Annual Review of Pharmacology and Toxicology (2009)

c-MYC is an important regulator of a wide array of cellular processes necessary for normal cell growth and differentiation, and its dysregulation is one of the hallmarks of many cancers. Consequently, understanding c-MYC transcriptional activation is critical for understanding developmental and cancer biology, as well as for the development of new anticancer drugs. The nuclease hypersensitive element (NHE) III(1) region of the c-MYC promoter has been shown to be particularly important in regulating c-MYC expression. Specifically, the formation of a G-quadruplex structure appears to promote repression of c-MYC transcription. This review focuses on what is known about the formation of a G-quadruplex in the NHE III(1) region of the c-MYC promoter, as well as on those factors that are known to modulate its formation. Last, we discuss the development of small molecules that stabilize or induce the formation of G-quadruplex structures and could potentially be used as anticancer agents.
IL-1 Blockade in Autoinflammatory Syndromes
Authors: Adriana A. Jesus, Raphaela Goldbach-Mansky
Journal: Annual Review of Medicine (2014)

Monogenic autoinflammatory syndromes present with excessive systemic inflammation including fever, rashes, arthritis, and organ-specific inflammation and are caused by defects in single genes encoding proteins that regulate innate inflammatory pathways. Pathogenic variants in two interleukin-1 (IL-1)–regulating genes, NLRP3 and IL1RN, cause two severe and early-onset autoinflammatory syndromes, CAPS (cryopyrin associated periodic syndromes) and DIRA (deficiency of IL-1 receptor antagonist). The discovery of the mutations that cause CAPS and DIRA led to clinical and basic research that uncovered the key role of IL-1 in an extended spectrum of immune dysregulatory conditions. NLRP3 encodes cryopyrin, an intracellular “molecular sensor” that forms a multimolecular platform, the NLRP3 inflammasome, which links “danger recognition” to the activation of the proinflammatory cytokine IL-1β. The success and safety profile of drugs targeting IL -1 in the treatment of CAPS and DIRA have encouraged their wider use in other autoinflammatory syndromes including the classic hereditary periodic fever syndromes (familial Mediterranean fever, TNF receptor–associated periodic syndrome, and hyperimmunoglobulinemia D with periodic fever syndrome) and additional immune dysregulatory conditions that are not genetically well defined, including Still's, Behcet's, and Schnitzler diseases. The fact that the accumulation of metabolic substrates such as monosodium urate, ceramide, cholesterol, and glucose can trigger the NLRP3 inflammasome connects metabolic stress to IL-1β-mediated inflammation and provides a rationale for therapeutically targeting IL-1 in prevalent diseases such as gout, diabetes mellitus, and coronary artery disease.
Tranilast Attenuates Structural and Functional Aspects of Renal Injury in the Remnant Kidney Model
Authors: Darren J. Kelly, Yuan Zhang, Renae Gow, Richard E. Gilbert
Journal: Journal of the American Society of Nephrology (2004)

Pathologic fibrosis is a key feature of progressive renal disease that correlates closely with kidney dysfunction and in which the prosclerotic growth factor TGF-beta has been consistently implicated. Tranilast (n-[3,4-dimethoxycinnamoyl] anthranilic acid), an antifibrotic agent that is used to treat hypertrophic scars and scleroderma, has also been shown to inhibit TGF-beta-induced extracellular matrix synthesis in a range of cell types, including those of renal origin. Therefore, the effects of tranilast on kidney fibrosis and dysfunction were examined in the subtotal nephrectomy model of progressive renal injury. Subtotal nephrectomy led to proteinuria and renal dysfunction in association with glomerulosclerosis, tubulointerstitial fibrosis, and macrophage accumulation. Despite persistent hypertension, treatment with tranilast led to a reduction in albuminuria (61.7 (x)/(/) 1.2 versus 20.5 (x)/(/) 1.3 mg/d; P < 0.01) and plasma creatinine (0.16 versus 0.08 mmol/L; P < 0.01) in subtotally nephrectomized rats. In addition, features suggestive of TGF-beta activation, including glomerulosclerosis, tubulointerstitial fibrosis, tubular atrophy, and macrophage accumulation, all were significantly attenuated by tranilast in association with evidence of reduced TGF-beta signaling in vivo. In the context of a recent pilot study in humans, the findings of the present report suggest that tranilast may provide a novel strategy for the treatment of progressive kidney disease characterized by fibrotic scarring.
Female Reproductive Health After Childhood, Adolescent, and Young Adult Cancers: Guidelines for the Assessment and Management of Female Reproductive Complications
Authors: Monika L. Metzger, Lillian R. Meacham, Briana Patterson, Jacqueline S. Casillas, Louis S. Constine, Nobuko Hijiya, Lisa B. Kenney, Marcia Leonard, Barbara A. Lockart, Wendy Likes, Daniel M. Green
Journal: Journal of Clinical Oncology (2013)

Purpose As more young female patients with cancer survive their primary disease, concerns about reproductive health related to primary therapy gain relevance. Cancer therapy can often affect reproductive organs, leading to impaired pubertal development, hormonal regulation, fertility, and sexual function, affecting quality of life. Methods The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancer (COG-LTFU Guidelines) are evidence-based recommendations for screening and management of late effects of therapeutic exposures. The guidelines are updated every 2 years by a multidisciplinary panel based on current literature review and expert consensus. Results This review summarizes the current task force recommendations for the assessment and management of female reproductive complications after treatment for childhood, adolescent, and young adult cancers. Experimental pretreatment as well as post-treatment fertility preservation strategies, including barriers and ethical considerations, which are not included in the COG-LTFU Guidelines, are also discussed. Conclusion Ongoing research will continue to inform COG-LTFU Guideline recommendations for follow-up care of female survivors of childhood cancer to improve their health and quality of life.
Purine analogs in marginal-zone lymphomas
Authors: S J Horning
Journal: Annals of Oncology (1996)

In an area of lymphoma classification still being defined, marginal-zone lymphomas have distinctive immunohistochemical and cytogenetic features that distinguish them from mantle-cell and follicular lymphomas. There are three subtypes: the extranodal mucosa-associated lymphoid tissue (MALT) lymphomas, the nodal monocytoid B-cell (MBCL) lymphomas, and the splenic marginal-zone lymphomas. The MALT lymphomas represent the neoplastic counterpart of the gut-associated lymphoid tissue, which extends from the jejunum to the rectum. They arise in sites usually containing no lymphoid tissue, such as the stomach, thyroid, and salivary gland. Gastric MALT lymphomas, the most common, are associated with Helicobacter pylori. The MBCL lymphomas closely resemble MALT lymphomas and unlike other non-Hodgkin's lymphomas are commonly composite. Therapy for these lymphomas may include radiation therapy or surgery when disease is of limited extent. However, gastrectomy for gastric MALT lymphomas is not in favor because of the efficacy of antibiotic regimens that can eliminate H. pylori infection. Splenectomy may be indicated for splenic lymphomas. Purine analogs are promising therapeutic agents because they are specific for lymphoid cells. Also, they may prove useful in indolent cancers such as these, because of their activity against dividing and resting cells. Purine analogs may be considered as second-line therapy after alkylating agents for these lymphomas.
Limitations and reliability of exercise electrocardiography tests in coronary heart disease
Authors: R J LINDEN, D A S G MARY
Journal: Cardiovascular Research (1982)

Journal Article Limitations and reliability of exercise electrocardiography tests in coronary heart disease Get access R J LINDEN, R J LINDEN From the Department of Cardiovascular Studies, The University, Leeds Address for correspondence and reprints: Prof R J Linden, Department of Cardiovascular Studies, The University, Leeds LS2 9JT, England. Search for other works by this author on: Oxford Academic PubMed Google Scholar D A S G MARY D A S G MARY From the Department of Cardiovascular Studies, The University, Leeds Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 16, Issue 12, December 1982, Pages 675–710, https://doi.org/10.1093/cvr/16.12.675 Published: 01 December 1982
Deletion of the pH Sensor GPR4 Decreases Renal Acid Excretion
Authors: Xuming Sun, Li V Yang, Brian C Tiegs, Lois J Arend, Dennis W McGraw, Raymond B Penn, Snezana Petrovic
Journal: Journal of the American Society of Nephrology (2010)

Proton receptors are G protein-coupled receptors that accept protons as ligands and function as pH sensors. One of the proton receptors, GPR4, is relatively abundant in the kidney, but its potential role in acid-base homeostasis is unknown. In this study, we examined the distribution of GPR4 in the kidney, its function in kidney epithelial cells, and the effects of its deletion on acid-base homeostasis. We observed GPR4 expression in the kidney cortex, in the outer and inner medulla, in isolated kidney collecting ducts, and in cultured outer and inner medullary collecting duct cells (mOMCD1 and mIMCD3). Cultured mOMCD1 cells exhibited pH-dependent accumulation of intracellular cAMP, characteristic of GPR4 activation; GPR4 knockdown attenuated this accumulation. In vivo, deletion of GPR4 decreased net acid secretion by the kidney and resulted in a nongap metabolic acidosis, indicating that GPR4 is required to maintain acid-base homeostasis. Collectively, these findings suggest that GPR4 is a pH sensor with an important role in regulating acid secretion in the kidney collecting duct.