tbuckley/cabot-search huggingface dataset:
Cancer- and Chemotherapy-Induced Anemia
Authors: George M Rodgers, Pamela Sue Becker, Charles L Bennett, David Cella, Asher Chanan-Khan, Carolyn Chesney, Charles Cleeland, Peter F Coccia, Benjamin Djulbegovic, Jennifer L Garst, Jeffrey A Gilreath, Eric H Kraut, Weei-Chin Lin, Ursula Matulonis, Michael Millenson, Denise Reinke, Joseph Rosenthal, Paul Sabbatini, Rowena N Schwartz, Richard S Stein, Ravi Vij
Journal: Journal of the National Comprehensive Cancer Network (2008)

Anemia is a common condition in patients with cancer, and its correction through either transfusion with packed red blood cells or the administration of erythropoiesis-stimulating agents (ESAs) is a supportive care measure. The purpose of the guidelines is to operationalize the evaluation and treatment of anemia in cancer patients and to enable patients and clinicians to evaluate treatment options in the context of risks and benefits. The updated guidelines include a number of important changes that respond to new FDA recommendations limiting the use of ESAs in cancer patients. Updates also include new tables on the risks and benefits of ESAs versus red blood cell transfusion and recommendations for administering parenteral iron products. For the most recent version of the guidelines, please visit NCCN.org
Upregulation of TRPM7 Channels by Angiotensin II Triggers Phenotypic Switching of Vascular Smooth Muscle Cells of Ascending Aorta
Authors: Zheng Zhang, Mi Wang, Xiao-Han Fan, Jing-Hui Chen, Yong-Yuan Guan, Yong-Bo Tang
Journal: Circulation Research (2012)

Angiotensin II (Ang II) has pleiotropic effects on vascular smooth muscle cells (VSMCs). It has been demonstrated to promote the proliferative phenotype of VSMCs in mouse ascending aorta, but the underlying mechanisms remain incompletely understood.The present study was designed to explore whether the Ca(2+)-permeable transient receptor potential melastatin 7 (TRPM7) channel is involved in Ang II-induced phenotype switching of ascending aortic VSMCs and to dissect the molecular mechanisms by which TRPM7 modulates VSMC phenotype.As revealed by current recording, Ang II infusion increased TRPM7 whole-cell currents in ascending aortic VSMCs. The increase in TRPM7 currents was found to result from enhanced expression of TRPM7 protein rather than elevated single-channel activity (open probability and slope conductance) and/or reduced Mg(2+)-mediated channel block. Mechanistically, Ang II elevated TRPM7 expression via Ang II type 1 receptor-mediated ERK1/2 signaling. As indicated by the expression levels of VSMC differentiation marker genes, phenotypic switching of ascending aorta occurred during Ang II infusion. Meanwhile, ERK1/2-Elk-1 signaling pathway known to suppress VSMC differentiation was activated in Ang II-infused ascending aorta. Knockdown of TRPM7 with small interfering RNA established a causative role of TRPM7 in Ang II-induced phenotypic change and promotion of cell proliferation. Moreover, TRPM7 was shown to be required for Pyk2-ERK1/2-Elk-1 pathway activation by Ang II, which potentiated TRPM7 channel function and thus activated the Ca(2+)-sensitive kinase Pyk2. Finally, TRPM7 knockdown attenuated Ang II-induced displacement of myocardin from SM22 promoter, but the effects could be reversed by expression of constitutively active c-Src.Our data establish that upregulation of TRPM7 channels by Ang II contributes to the development of the proliferative phenotype of ascending aortic VSMCs, and TRPM7 channel suppresses VSMC gene expression via Ca(2+) influx-mediated activation of Pyk2-ERK1/2-Elk-1 pathway.
Cutaneous hypersensitivity reactions due to thiacetazone in HIV-1 seropositive patients treated for tuberculosis
Authors: P Nunn, R Brindle, K Wasunna, C Gilks, M Omwega, J Were, M Med, P Nunn, D Kibuga, S Gathua, A Imalingat, P Nunn, K Wasunna, S Lucas, K McAdam, R Brindle, S Lucas, C Gilks
Journal: The Lancet (1991)
Pulmonary Resection for Tuberculosis in Children
Authors: C. A. Ross
Journal: Thorax (1951)

The literature concerning resection for tuberculosis gives scattered references to resection in children, but as far as I know the only paper published on the subject has been that of Levitin and Zelman in 1950.These authors reported four cases of pneumonectomy in the age group 3 to 13 years.These operations were all performed in coloured patients, who had little natural immunity, and, of the four, three had done well.The fourth patient died of a contralateral activation of disease, which was present at th-time of the operation.Pneumonectomy in the fatal case was performed before streptomycin was available as a cover for the procedure.The three successful cases were patients who had no evidence of contralateral disease.In two of the four the resection was performed for " destroyed lung."The other two were for basal cavities, one of which extended across the fissure to the upper lobe, and the other was confined to the lower lobe, but in this case lobectomy proved to be technically too difficult and a pneumonectomy was performed.Seven lobectomies and six pneumonectomies have been done on 12 children by surgeons of the Northern Regional Thoracic Surgery Centre for Newcastle-upon-Tyne at Shotley Bridge Hospital and Poole Sanatorium.With the exception of one patient aged 16, all the patients have been under 15 years of age.Although 12 may be too small a series from which to draw conclusions, the results to date are favourable, and it is suggested that this may be the method of treatment for certain types of the disease in children.The pneumonectomies were performed for extensive unilateral disease, except in one case, where there was evidence of contralateral activity (Case 5).Of the lobec- tomies, three were performed where other methods were ineffective in controlling the disease; three were performed as a method of choice; and one was done as an emergency procedure to prevent the rupture of a cavity under artificial pneumothorax.The radiographs illustrate the two series, pneumonectomies and lobectomies. PRE-OPERATIVE TREATMENTAll patients, except two, were given a period of sanatorium treatment before resection was decided upon.Nine of the 12 patients received streptomycin, and some had P.A.S. in appropriate doses pre-operatively.Every possible method was used to bring the patient into as good general con- dition as possible before operation.A high-protein diet, vitamins, iron, and, where necessary, blood transfusion were used.A patient was considered to be ideally fit for surgery if the temperature remained normal, the sedimentation rate was stable 2D on July 21,
Genetic and epigenetic instability in human pluripotent stem cells
Authors: H.T. Nguyen, M. Geens, C. Spits
Journal: Human Reproduction Update (2012)

There is an increasing body of evidence that human pluripotent stem cells (hPSCs) are prone to (epi)genetic instability during in vitro culture. This review aims at giving a comprehensive overview of the current knowledge on culture-induced (epi)genetic alterations in hPSCs and their phenotypic consequences. Combinations of the following key words were applied as search criteria: human induced pluripotent stem cells and human embryonic stem cells in combination with malignancy, tumorigenicity, X inactivation, mitochondrial mutations, genomic integrity, chromosomal abnormalities, culture adaptation, aneuploidy and CD30. Only studies in English, on hPSCs and focused on (epi)genomic integrity were included. Further manuscripts were added from cross-references. Numerous (epi)genetic aberrations have been detected in hPSCs. Recurrent genetic alterations give a selective advantage in culture to the altered cells leading to overgrowth of abnormal, culture-adapted cells. The functional effects of these alterations are not yet fully understood, but suggest a (pre)malignant transformation of abnormal cells with decreased differentiation and increased proliferative capacity. Given the high degree of (epi)genetic alterations reported in the literature and altered phenotypic characteristics of the abnormal cells, controlling for the (epi)genetic integrity of hPSCs before any clinical application is an absolute necessity.
An amicus for the defense: Relational reasoning magnifies the behavioral differences between humans and nonhumans
Authors: Arthur B. Markman, C. Hunt Stilwell
Journal: Behavioral and Brain Sciences (2008)

Abstract Relational representation abilities are a crucial cognitive difference between human and nonhuman animals. We argue that relational reasoning and representation supports the development of culture that increases in complexity. Thus, these abilities are a force that magnifies the apparent difference in cognitive abilities between humans and nonhumans.
Changes in causes of death in systemic sclerosis, 1972-2002
Authors: V. D Steen, T. A Medsger
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> Survival of scleroderma has changed since the renal crisis treatment has become possible. <b>Aims:</b> To document the changes in survival and organ system causes of mortality in systemic sclerosis (SSc) over the past 25 years in patients from a single medical centre. <b>Methods:</b> Consecutive patients evaluated at the University of Pittsburgh, Pittsburgh, Pennsylvania, USA between 1 January 1972 and 31 December 1996 were studied. Survival was determined in five 5-year time periods between 1972 and 1997. Causes of death included scleroderma-related (scleroderma renal crisis, pulmonary arterial hypertension, pulmonary fibrosis (PF), gastrointestinal (GI), heart and multiorgan failure) and non-scleroderma-related (cancer, atherosclerotic cardiovascular or cerebrovascular disease, infection, sudden death, other and unknown) causes. <b>Results:</b> The 10-year survival improved steadily from 54% to 66% during each of the time intervals. There was a significant improvement in survival for patients during 1982–91 compared with those during 1972–81 (p&lt;0.001), even when patients with renal crisis were excluded (p&lt;0.005). The frequency of deaths due to renal crisis significantly decreased over the 30-year time period, from 42% to 6% of scleroderma-related deaths (p&lt;0.001), whereas the proportion of patients with scleroderma who died of PF increased from 6% to 33% (p&lt;0.001). The frequency of pulmonary hypertension, independent of PF, also significantly increased during this time period (p&lt;0.05). There were no changes in scleroderma GI- and heart-related deaths, nor in any of the non-scleroderma-related causes, although patients with scleroderma were less likely to die from scleroderma-related problems in the past 15 years. <b>Conclusion:</b> The change in the pattern of scleroderma-related deaths over the past 30 years demonstrates that the lung (both pulmonary hypertension and PF) is the primary cause of scleroderma-related deaths today. It is important that aggressive searches continue to develop better therapies for these severe pulmonary complications of SSc.
Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia
Authors: C Feinle
Journal: Gut (2001)

<h3>BACKGROUND/AIMS</h3> We aimed to evaluate the role of fat and cholecystokinin (CCK) in the pathophysiology of functional dyspepsia (FD) by investigating symptoms and plasma CCK levels following increasing doses of duodenal lipid during gastric distension, and the effect of CCK-A receptor blockade. <h3>SUBJECTS/METHODS</h3> In study A, six FD patients were studied on three occasions during duodenal infusion of saline or lipid (1.1 (L-1) or 2 kcal/min (L-2)) and proximal gastric distensions. Six healthy subjects were also studied as controls during L-2 only. In study B, the effect of the CCK-A antagonist dexloxiglumide (5 mg/kg/h) on L-2 induced symptoms was studied in 12 FD patients. Changes in gastric volume at minimal distending pressure and plasma CCK (study A) were assessed, gastric distensions were performed using a barostat, and dyspeptic symptoms were monitored. <h3>RESULTS</h3> Lipid increased gastric volume compared with saline (ΔV (ml): saline 15 (20), L-1 122 (42), L-2 114 (28)) in patients and even more so in controls (221 (37); p&lt;0.05). During distensions, symptoms were greater during L-2 than during saline or L-1, and greater in patients than in controls, while gastric compliance was smaller in patients than in controls (p&lt;0.05). Lipid increased plasma CCK levels in patients and controls (p&gt;0.05). Dexloxiglumide abolished the increase in gastric volume (ΔV (ml): dexloxiglumide 17 (9), placebo 186 (49)) and dyspeptic symptoms (sum of scores: dexloxiglumide 24 (7), placebo 44 (19)) during duodenal lipid infusion. Dexloxiglumide also reduced gastric compliance (ml/mm Hg: dexloxiglumide 51 (7), placebo 72 (11)) and symptoms (sum of scores: dexloxiglumide 101 (17), placebo 154 (21)) during gastric distension. <h3>CONCLUSION</h3> CCK-A receptors are involved in the generation of dyspeptic symptoms by duodenal lipid during gastric distension.
Prospective Study of Alcohol Consumption and Risk of Dementia in Older Adults
Authors: Kenneth J. Mukamal, Lewis H. Kuller, Annette L. Fitzpatrick, W. T. Longstreth, Murray A. Mittleman, David S. Siscovick
Journal: JAMA (2003)

Context Alcohol consumption has been associated with complex changes in cerebral vasculature and structure in older adults. How alcohol consumption affects the incidence of dementia is less clear. Objective To determine the prospective relationship of alcohol consumption and risk of dementia among older adults. Design, Setting, and Participants Nested case-control study of 373 cases with incident dementia and 373 controls who were among 5888 adults aged 65 years and older who participated in the Cardiovascular Health Study, a prospective, population-based cohort study in 4 US communities. The controls were frequency-matched on age, death before 1999, and their attendance of a 1998-1999 clinic. Participants in this study underwent magnetic resonance imaging (MRI) of the brain and cognitive testing between 1992 and 1994 and were followed up until 1999. Main Outcome Measures Odds of incident dementia, ascertained by detailed neurological and neuropsychological examinations according to average alcohol consumption, assessed by self-reported intake of beer, wine, and liquor at 2 visits prior to the date of the MRI. Results Compared with abstention, the adjusted odds for dementia among those whose weekly alcohol consumption was less than 1 drink were 0.65 (95% confidence interval [CI], 0.41-1.02); 1 to 6 drinks, 0.46 (95% CI, 0.27-0.77); 7 to 13 drinks, 0.69 (95% CI, 0.37-1.31); and 14 or more drinks, 1.22 (95% CI, 0.60-2.49; P for quadratic term = .001). A trend toward greater odds of dementia associated with heavier alcohol consumption was most apparent among men and participants with an apolipoprotein E ϵ4 allele. We found generally similar relationships of alcohol use with Alzheimer disease and vascular dementia. Conclusions Compared with abstention, consumption of 1 to 6 drinks weekly is associated with a lower risk of incident dementia among older adults.
Essential Role of the Prosurvival bcl-2 Homologue A1 in Mast Cell Survival After Allergic Activation
Authors: Zou Xiang, Ahmed A. Ahmed, Christine Möller, Kei-ichi Nakayama, Shigetsugu Hatakeyama, Gunnar Nilsson
Journal: The Journal of Experimental Medicine (2001)

Mast cells reside in tissues, where upon activation through the high-affinity-IgE-receptor (FcϵRI) they degranulate and orchestrate the allergic reaction. Mast cells survive this activation and can thus be reactivated. In this study we demonstrate that this process depends on the pro-survival gene A1. Activation of mast cells through FcϵRI resulted in degranulation, strong induction of A1 mRNA and protein, and cell survival. In contrast, A1-deficient mast cells released granule mediators similar to the wild-type control, but the cells did not survive an allergic activation. Furthermore, A1−/− mice that had been sensitized and provocated with allergen exhibited a lower number of mast cell compared with littermate controls. The induction of A1 was dependent on calcium, as EDTA prevented A1 expression. The calcium ionophore, ionomycin, induced A1 expression and mast cell survival, whereas compound 48/80, a well-known mast cell secretagogue, did not. This study uncovers the importance of A1 for mast cell survival in allergic reactions, and it proposes A1 as a potential target for the treatment of allergic diseases.
IFNα and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease activity in systemic lupus erythematosus
Authors: Thomas Rose, Andreas Grützkau, Heike Hirseland, Dörte Huscher, Cornelia Dähnrich, Andrzej Dzionek, Tobias Ozimkowski, Wolfgang Schlumberger, Philipp Enghard, Andreas Radbruch, Gabriela Riemekasten, Gerd-Rüdiger Burmester, Falk Hiepe, Robert Biesen
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To evaluate and compare the clinical efficacy of three biomarkers for interferon (IFN) activity (measured directly and indirectly) and six traditional biomarkers in indicating current and prospective disease activity (DA) in systemic lupus erythematosus (SLE). <h3>Methods</h3> IFNα (dissociation-enhanced lanthanide fluorescent immunoassay), IFNγ-inducible protein 10 (IP-10) (ELISA) and sialic acid-binding Ig-like lectin 1 (SIGLEC-1) (flow cytometry) were measured in 79 accurately characterised patients with lupus and compared with serum titres of Anti-dsDNA (ELISA and radioimmunoassay), Anti-dsDNA-NcX ELISA, Anti-Nuc ELISA, and complement C3 and C4. DA was evaluated using the British Isles Lupus Assessment Group 2004 Index (BILAG-2004) and a modified SLE Disease Activity Index-2000 (mSLEDAI-2K). In addition, 31 clinically quiescent patients were monitored for flares over the course of 180 days. <h3>Results</h3> Increased levels of IFNα, IP-10 and SIGLEC-1 were found in 32%, 50% and 86%, respectively, of 66 patients with active SLE. IFNα (r=0.45; p&lt;0.0001) and SIGLEC-1 (r=0.54; p&lt;0.0001) correlated better with BILAG-2004 than did IP-10 (r=0.38; p=0.0002), Farr assay (r=0.40; p=0.0001), Anti-dsDNA-NcX ELISA (r=0.28; p=0.0061), Anti-dsDNA ELISA (r=0.31; p=0.0025), Anti-Nuc ELISA (r=0.25; p=0.0121), C3 (r=−0.43; p&lt;0.0001) and C4 (r=−0.33; p=0.0013). Predictors of SLE flares were disease duration ≤92 months, mild clinical activity (in contrast with no activity), complement C3≤89 mg/dl and IFNα≥20 pg/ml, while only lymphocyte count and age were independent predictors in multivariate analysis. <h3>Conclusions</h3> IFNα, IP-10 and SIGLEC-1 emerged as beneficial biomarkers of DA in patients with SLE. Therefore the implementation of IFN biomarkers in standard lupus diagnostics should be reappraised, especially in view of emerging anti-IFN-directed therapies.
Molecular classification of gliomas based on whole genome gene expression: a systematic report of 225 samples from the Chinese Glioma Cooperative Group
Authors: Wei Yan, Wei Zhang, Gan You, Junxia Zhang, Lei Han, Zhaoshi Bao, Yongzhi Wang, Yanwei Liu, Chuanlu Jiang, Chunsheng Kang, Yongping You, Tao Jiang
Journal: Neuro-Oncology (2012)

Defining glioma subtypes based on objective genetic and molecular signatures may allow for a more rational, patient-specific approach to molecularly targeted therapy. However, prior studies attempting to classify glioma subtypes have given conflicting results. We aim to complement and validate the existing molecular classification system on a large number of samples from an East Asian population. A total of 225 samples from Chinese patients was selected for whole genome gene expression profiling. Consensus clustering was applied. Three major groups of gliomas were identified (referred to as G1, G2, and G3). The G1 subgroup correlates with a good clinical outcome, young age, and extremely high frequency of IDH1 mutations. Relative to the G1 subgroup, the G3 subgroup is correlated with a poorer clinical outcome, older age, and a very low rate of mutations in the IDH1 gene. Correlations of the G2 subgroup with respect to clinical outcome, age, and IDH1 mutation fall between the G1 and G3 subgroups. In addition, the G2 subtype was associated with a higher percentage of loss of 1p/19q when compared with G1 and G3 subtypes. Furthermore, our classification scheme was validated on 2 independent datasets derived from the cancer genome atlas (TCGA) and Rembrandt. With use of the TCGA classification system, proneural, neural, and mesenchymal, but not classical subtype, associated gene signatures were clearly defined. In summary, our results reveal that 3 main subtypes stably exist in Chinese patients with glioma. Our classification scheme may reflect the clinical and genetic alterations more clearly. Classical subtype–associated gene signature was not found in our dataset.
Cancer Incidence Among Danish Thorotrast-Exposed Patients
Authors: M. Andersson, H. H. Storm
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Studies of group of patients given injections of the alpha-emitting x-ray contrast medium Thorotrast may provide information on human alpha-ray carcino-genesis. Purpose : We re-established a formerly identified cohort of neurological patients receiving injections of Thorotrast for cerbral arteriograohy and assessed their incidence of cancer. Methods : Using the national population register, the Danish Cancer Registry, and other registers, we determined the incidence of cancer among Thorotrast-injected population and computed for different cancer sites. Results : The cumulative risk for cancer at all sites (excluding brain tumors where the standardized incidence ratio [SIR] was 28) reacahed 86%50 years after Thorotrast injection. SIR was greatly elevated at all sites except the brain and CNS (3.3, 95% confidence interval =3.0–3.7), mainly because of liver cancers (SIR = 126) as well as leukemia (SIR = 10)for which a relationship was found between the time since injection and the estimated dose (but not the age at injection). Other sites with significantly increased risks of cancer included the gallboladder and extrahepatic bile ducts (SIR =14), peritoneum (SIR = 8.6), sites of multiple myeloma (SIR = 4.6), metastatic sites (SIR = 12), and unspecified sites (SIR = 11). Cancers of the lung and breast also occured in significant excess, but no relationship between SIR and volum of injected Thorotrast or time since injection was observed. Cancer risk was increased at most other sites, although this increase was not statistically signigicant. Conclusion : Alpha radiation may account for the increased risk of tumors of the liver, gallbladder, and peritoneum as well as leukemia and multiple myeloma, whereas confounding factors most probably contribute to the increased risks at other sites. [J Natl Cancer Inst 84: 1318–1325, 1992]