tbuckley/cabot-search huggingface dataset:
Copy Number Losses Define Subgroups of Dedifferentiated Liposarcoma with Poor Prognosis and Genomic Instability
Authors: Aimee M. Crago, Nicholas D. Socci, Penelope DeCarolis, Rachael O'Connor, Barry S. Taylor, Li-Xuan Qin, Cristina R. Antonescu, Samuel Singer
Journal: Clinical Cancer Research (2012)

Molecular events underlying progression of well-differentiated liposarcoma (WDLS) to dedifferentiated liposarcoma (DDLS) are poorly defined. This study sought to identify copy number alterations (CNA) associated with dedifferentiation of WDLS, with DDLS morphology, and with patient outcomes.Fifty-five WDLS and 52 DDLS were analyzed using Agilent 244K comparative genomic hybridization and Affymetrix U133A expression arrays. CNAs were identified by RAE analysis. Thirty-nine of the DDLS specimens were categorized morphologically by a single pathologist.Nine regions of CNA were identified as recurrent in DDLS but not WDLS; 79% of DDLS had at least one of these CNAs. Loss of the chromosome segment 11q23-24, the most common event, was observed only in DDLS that morphologically resembled the genomically complex sarcomas, undifferentiated pleomorphic sarcoma and myxofibrosarcoma. 11q23-24 loss was itself associated with increased genomic complexity in DDLS. Loss of 19q13, but not 11q23-24, was associated with poor prognosis. Median disease-specific survival was shorter for patients with19q13 loss (27 months) than for patients with diploid 19q13 (>90 months; P < 0.0025), and 19q13 loss was associated with local recurrence (HR, 2.86; P = 0.013). Common copy number losses were associated with transcriptional downregulation of potential tumor suppressors and adipogenesis-related genes (e.g., EI24 and CEBPA).Dedifferentiation of WDLS is associated with recurrent CNAs in 79% of tumors. In DDLS, loss of 11q23-24 is associated with genomic complexity and distinct morphology whereas loss of 19q13 predicts poor prognosis. CNAs in liposarcoma improve risk stratification for patients and will help identify potential tumor suppressors driving liposarcoma progression.
Concurrent measurement of smooth muscle shortening, lumen narrowing and flow to acetylcholine in large and small porcine bronchi
Authors: HW Mitchell, R Cvetkovski, MP Sparrow, PR Gray, PK McFawn
Journal: European Respiratory Journal (1998)

Models of airway function indicate that responsiveness (flow reduction) to bronchoconstrictor provocation depends on airway smooth muscle shortening and airway wall morphology. The contribution of these factors to the responsiveness of central and peripheral bronchi was assessed. Lumen flow was recorded in porcine perfused small (2 min i.d.) and large bronchial segments (6 mm i.d.). Lumen diameter was recorded in the same airways after inserting an endoscope. Smooth muscle shortening, relative wall area (WAr), smooth muscle and cartilage thickness and mucosal folds were measured morphometrically. The effect of acetylcholine (ACh; 10(-6)-10(-1) M) on functional measurements was determined by curve fitting. Maximum muscle shortening was 30% in small and 19% in large bronchi (p&lt;0.01) and lumen narrowing was 49% and 39%, respectively. High doses of ACh stopped flow in small bronchi, but produced a plateau in large bronchi. Small airways were 250-times more sensitive to ACh than large airways, for all measurements. Smooth muscle and cartilage thickness and numbers of mucosal folds were greater in large than in small bronchi (p&lt; or =0.01). Lumen narrowing and flow reduction were greater than predicted on the basis of muscle shortening and WAr (p&lt;0.05). The structure of airways from the two groups was qualitatively similar, but responses were markedly different. Greater narrowing and flow responses of small bronchi were directly associated with smooth muscle responsiveness in situ. The results suggest that in vivo changes in airway wall shape or dimensions, or luminal secretions, exert a significant effect on airway flow, particularly in the small airways.
The Emergence of Group B Streptococci in Infections of the Newborn Infant
Authors: B F Anthony, D M Okada
Journal: Annual Review of Medicine (1977)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Apolipoprotein J/Clusterin Is Induced in Vascular Smooth Muscle Cells After Vascular Injury
Authors: Masaaki Miyata, Sadatoshi Biro, Hiroshi Kaieda, Hideyuki Eto, Koji Orihara, Takashi Kihara, Hachiro Obata, Noriko Matsushita, Takami Matsuyama, Chuwa Tei
Journal: Circulation (2001)

Background — Understanding the precise molecular mechanisms underlying the phenomenon of restenosis after PTCA may help us to develop a new strategy for the treatment of restenosis after PTCA. The purpose of this study was to identify the genes involved in vascular restenosis. Methods and Results — Applying a differential hybridization method to a model of the balloon-injured rabbit aorta, we identified 6 cDNA clones that were upregulated after injury. Northern blot showed that 5 genes, but not apolipoprotein J (apoJ)/clusterin, were constitutively expressed in noninjured aorta and upregulated after balloon injury. ApoJ mRNA was not detectable in noninjured aorta (control), began to be expressed at 6 hours after injury, showed a peak level at 24 hours (a 48-fold increase), gradually declined, and returned to the control level at 24 weeks. Western blot and immunohistochemistry demonstrated no expression of apoJ protein in noninjured aorta, an expression of apoJ at 2 days after balloon injury, and a peak level (a 55-fold increase) at 2 to 8 weeks. The expression of apoJ protein continued until 24 weeks after injury. In situ hybridization revealed that apoJ mRNA was expressed in smooth muscle cells (SMCs) of media at 2 days after injury and in SMCs of media and neointima at 2 weeks. To analyze the function of apoJ, stably transfected rabbit SMCs were created. The expression of apoJ stimulated proliferation and migration of SMCs. Conclusions — ApoJ is dramatically induced in media and neointima after vascular injury, suggesting that apoJ contributes to restenosis after angioplasty.
Great Toe of This Assembly
Authors: Liam Farrell
Journal: BMJ (2006)

Referring to yourself in the third person usually signifies an unpleasantly inflated ego—for example, “The Lady's not for turning.” But I can do better, with echoes of the politically incorrect “Liver in ward 3.”

It was a cold winter's night, and the wind was moaning through the eaves like a patient having an ingrown toenail removed who has been given too little local anaesthetic (come on, haven't we all done it?), the kind of night when …
Serum-free light chain assessment in hepatitis C virus-related lymphoproliferative disorders
Authors: B Terrier, D Sène, D Saadoun, P Ghillani-Dalbin, V Thibault, A Delluc, J-C Piette, P Cacoub
Journal: Annals of the Rheumatic Diseases (2008)

Objective: To evaluate the relevance of serum-free light chain (FLC) assessment in hepatitis C virus (HCV)-related lymphoproliferative disorders, including mixed cryoglobulinemia (MC) and B cell non-Hodgkin lymphoma (B-NHL). Patients and methods: A total of 59 patients infected with HCV were prospectively followed, including patients without MC (n = 17), with asymptomatic MC (n = 7) and with MC vasculitis (n = 35, 9 of whom had B-NHL). Clinical and biological data were recorded at the time of the initial evaluation and at the end of follow-up. Serum FLC quantitation was carried out using a serum FLC assay. Results: The mean (SD) serum κ FLC level was higher in patients with asymptomatic MC (27.9 (8.6) mg/litre), MC vasculitis (36.7 (46.2) mg/litre) and B-NHL (51.3 (78.3) mg/litre) than without MC (21.7 (17.6) mg/litre) (p = 0.047, 0.025 and 0.045, respectively). The mean serum FLC ratio was higher in patients with MC vasculitis (2.08 (2.33)) and B-NHL (3.14 (3.49)) than in patients without MC (1.03 (0.26)) (p = 0.008). The rate of abnormal serum FLC ratio (&gt;1.65) correlated with the severity of HCV-related B cell disorder: 0/17 (0%) without MC, 0/7 (0%) asymptomatic MC, 6/26 (23%) MC vasculitis without B-NHL and 4/9 (44%) B-NHL (p = 0.002). Serum κ FLC levels and the serum FLC ratio correlated with the cryoglobulin level (r = 0.32, p&lt;0.001 and r = 0.25, p = 0.002, respectively) and the severity of the B cell disorder (r = 0.26, p = 0.045 and r = 0.41, p = 0.001, respectively). Among patients with an abnormal serum FLC ratio at baseline, the FLC ratio correlated with the virological response to HCV treatment. Conclusions: In patients infected with HCV, an abnormal serum FLC ratio appears to be a very interesting marker, as it is consistently associated with the presence of MC vasculitis and/or B-NHL. After antiviral therapy, the serum FLC ratio could be used as a surrogate marker of the control of the HCV-related lymphoproliferation.
“Economic man” in cross-cultural perspective: Behavioral experiments in 15 small-scale societies
Authors: Joseph Henrich, Robert Boyd, Samuel Bowles, Colin Camerer, Ernst Fehr, Herbert Gintis, Richard McElreath, Michael Alvard, Abigail Barr, Jean Ensminger, Natalie Smith Henrich, Kim Hill, Francisco Gil-White, Michael Gurven, Frank W. Marlowe, John Q. Patton, David Tracer
Journal: Behavioral and Brain Sciences (2005)

Researchers from across the social sciences have found consistent deviations from the predictions of the canonical model of self-interest in hundreds of experiments from around the world. This research, however, cannot determine whether the uniformity results from universal patterns of human behavior or from the limited cultural variation available among the university students used in virtually all prior experimental work. To address this, we undertook a cross-cultural study of behavior in ultimatum, public goods, and dictator games in a range of small-scale societies exhibiting a wide variety of economic and cultural conditions. We found, first, that the canonical model – based on self-interest – fails in all of the societies studied. Second, our data reveal substantially more behavioral variability across social groups than has been found in previous research. Third, group-level differences in economic organization and the structure of social interactions explain a substantial portion of the behavioral variation across societies: the higher the degree of market integration and the higher the payoffs to cooperation in everyday life, the greater the level of prosociality expressed in experimental games. Fourth, the available individual-level economic and demographic variables do not consistently explain game behavior, either within or across groups. Fifth, in many cases experimental play appears to reflect the common interactional patterns of everyday life.
Identification of a genetic variant for joint damage progression in autoantibody-positive rheumatoid arthritis
Authors: Rachel Knevel, Kerstin Klein, Klaartje Somers, Caroline Ospelt, Jeanine J Houwing-Duistermaat, Jessica A B van Nies, Diederik P C de Rooy, Laura de Bock, Fina A S Kurreeman, Joris Schonkeren, Gerrie Stoeken-Rijsbergen, Quinta Helmer, Michael P M van der Linden, Marlena Kern, Nataly Manjarrez-Orduno, Luis Rodriguez-Rodriquez, Piet Stinissen, Tom W J Huizinga, Rene E M Toes, Steffen Gay, Peter K Gregersen, Veerle Somers, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Joint destruction is a hallmark of autoantibody-positive rheumatoid arthritis (RA), though the severity is highly variable between patients. The processes underlying these interindividual differences are incompletely understood. <h3>Methods</h3> We performed a genome-wide association study on the radiological progression rate in 384 autoantibody-positive patients with RA. In stage-II 1557 X-rays of 301 Dutch autoantibody-positive patients with RA were studied and in stage-III 861 X-rays of 742 North American autoantibody-positive patients with RA. Sperm-Associated Antigen 16 (<i>SPAG16)</i> expression in RA synovium and fibroblast-like synoviocytes (FLS) was examined using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry. FLS secrete metalloproteinases that degrade cartilage and bone. <i>SPAG16</i> genotypes were related to matrix metalloproteinase (MMP)-3 and MMP-1 expression by FLS in vitro and MMP-3 production ex vivo. <h3>Results</h3> A cluster of single nucleotide polymorphisms (SNPs) at 2q34, located at <i>SPAG16</i>, associated with the radiological progression rate; rs7607479 reached genome-wide significance. A protective role of rs7607479 was replicated in European and North American patients with RA. Per minor allele, patients had a 0.78-fold (95% CI 0.67 to 0.91) progression rate over 7 years. mRNA and protein expression of SPAG16 in RA synovium and FLS was verified. FLS carrying the minor allele secreted less MMP-3 (p=1.60×10<sup>−2</sup>). Furthermore, patients with RA carrying the minor allele had lower serum levels of MMP-3 (p=4.28×10<sup>−2</sup>). In a multivariate analysis on rs7607479 and MMP-3, only MMP-3 associated with progression (p=2.77×10<sup>−4</sup>), suggesting that the association between <i>SPAG16</i>-rs7607479 and joint damage is mediated via an effect on MMP-3 secretion. <h3>Conclusions</h3> Genetic and functional analyses indicate that <i>SPAG16</i> influences MMP-3 regulation and protects against joint destruction in autoantibody-positive RA. These findings could enhance risk stratification in autoantibody-positive RA.
Roll Back Malaria: a failing global health campaign
Authors: Gavin Yamey
Journal: BMJ (2004)

Only increased donor support for malaria control can save it 

Roll Back Malaria was launched in 1998 bringing together multilateral, bilateral, nongovernmental, and private organisations. It made a clear pledge—to halve deaths from malaria by 2010. African heads of state endorsed the pledge at a summit in Abuja, Nigeria, in 2000.1 This endorsement was vital because 90% of the one million annual deaths from malaria are in Africa, mostly in young children and pregnant women.2 With just six years to go we have reached the halfway point since the pledge. How is Roll Back Malaria doing?

A graph distributed at the most recent Roll Back Malaria board meeting in New York, based on data from the World Health Reports 1999-2003, shows that the annual number of deaths worldwide from malaria is higher now than in 1998 (see bmj.com). The Africa Malaria Report 2003, published by Unicef and the World Health Organization, two of the biggest players in Roll Back Malaria, admits that “Roll Back Malaria is acting against a background of increasing malaria burden.”3 This statement is passive, and seems to absolve the campaign of responsibility. …
Amastigotes of Trypanosoma cruzi sustain an infective cycle in mammalian cells.
Authors: V Ley, N W Andrews, E S Robbins, V Nussenzweig
Journal: The Journal of Experimental Medicine (1988)

The two main stages of development of the protozoan parasite Trypanosoma cruzi found in the vertebrate host are the trypomastigote and the amastigote. It has been generally assumed that only trypomastigotes are capable of entering cells and that amastigotes are the intracellular replicative form of the parasite. We show here that after incubation for 4 h with human monocytes in vitro 90% or more of extracellularly derived (24 h) amastigotes of T. cruzi are taken up by the cells. Within 2 h they escape the phagocytic vacuole and enter the cytoplasm, where they divide and after 4-5 d transform into trypomastigotes. Trypomastigotes also invade cultured human monocytes. However, they show a lag of several hours between invasion and the start of DNA duplication, while amastigotes commence replication without an apparent lag. Amastigotes also infect cultured fibroblasts, albeit with lower efficiency. When injected intraperitoneally into mice, amastigotes are as infective as trypomastigotes. Based on these results, and on prior findings that amastigotes are found free in the circulation of mice during the acute stage of the disease (3), it seems likely that the cellular uptake of amastigotes can initiate an alternative subcycle within the life cycle of this parasite in the mammalian host. Also, because trypomastigotes and amastigotes have diverse surface antigens, they may use different strategies to invade host cells.
Clinicians learn less and less about more and more until they know nothing about everything; researchers learn more and more about less and less until they know everything about nothing: Discuss
Authors: Kenneth John Aitken
Journal: Behavioral and Brain Sciences (2012)

A number of recent developments in our understanding of the biology of heritability question commonly held views on the immutability of genetic factors. These have numerous potential implications for improving understanding and practice in pre- and postconceptional care and for infant and child mental health, and they carry a cautionary message against overgeneralization.
Neurological complications in patients with cutaneous T-cell lymphoma
Authors: H.J. SENTIS, G. PADBERG, O.J.S. BURUMA, G.TH.A.M. BOTS, R. WILLEMZE, W.A. VLOTEN
Journal: British Journal of Dermatology (1986)

Five patients with a cutaneous T-cell lymphoma (four with mycosis fungoides and one with a primary cutaneous T-immunoblastic lymphoma) who developed neurological sequelae are reported. In four of them, central nervous system involvement could be demonstrated at autopsy. The importance of early cerebrospinal fluid examination in these patients is stressed.
Different Progression of Tumor Xenografts between Mucin-Producing and Mucin–Non-Producing Mammary Adenocarcinoma-Bearing Mice
Authors: Ippei Sugihara, Masanobu Yoshida, Tatsuro Shigenobu, Hiroaki Takagi, Koji Maruyama, Noriko Takeuchi, Munetoyo Toda, Mizue Inoue, Hiroshi Nakada
Journal: Cancer Research (2006)

Previously, we found that MUC2 mucins could activate monocytes/macrophages through a scavenger receptor leading to cyclooxygenase (COX) 2 induction and overproduction of prostaglandin E2 (PGE2). To investigate the role of mucins in the tumor-bearing state, we compared s.c. tumor formation by using mucin-producing (TA3-Ha) and mucin-non-producing (TA3-St) cloned variants of mouse mammary adenocarcinomas. Expression of COX2 mRNA and protein and production of PGE2 were elevated in peritoneal macrophages stimulated with epiglycanin, which is a mucin-like glycoprotein produced by TA3-Ha cells. S.c. tumor tissues comprising TA3-Ha cells grew much faster than tissues comprising TA3-St cells. COX2 protein and vascular endothelial growth factor in TA3-Ha tumor tissues were elevated compared with the TA3-St tumor tissues. Although similar numbers of macrophages were observed immunochemically in the two types of tumor tissues, COX2 was induced prominently in the infiltrating macrophages in TA3-Ha tumor tissues but only faintly in TA3-St tumor tissues. Furthermore, angiogenesis progressed remarkably in TA3-Ha tumor tissues but only slightly in TA3-St tumor tissues. Epiglycanin-induced overproduction of PGE2 down-regulated interleukin-12 production by macrophages. IFN-gamma-producing CD4 T cells in spleens obtained from TA3-Ha tumor-bearing mice were significantly reduced compared with TA3-St tumor-bearing mice, suggesting that mucins cause PGE2-mediated immune suppression. Actually, the tumor growth of a TA3-Ha cell xenograft was suppressed effectively by oral administration of a COX2 inhibitor but that of a TA3-St cell one was not. These results suggest that mucins play an important role in tumor progression through overproduction of PGE2.
The neutrophilic and fibrinolytic response to talc can predict the outcome of pleurodesis
Authors: K. Psathakis
Journal: European Respiratory Journal (2006)

It was hypothesised that monitoring neutrophil and d-dimer (DD) levels into the pleural fluid, after talc instillation, could predict the outcome of pleurodesis. The current authors investigated a total of 168 patients with malignant pleural effusion, who were treated with talc poudrage. According to the outcome the patients were categorised into one of two groups, either successful or failed pleurodesis. In all cases, pleural fluid neutrophils and DDs were determined on serial measurements at 0, 3, 24 and 48 h after the procedure. The time course of these parameters was assessed in both groups and the time point at which they could better predict the outcome was further explored. Neutrophils rose rapidly after talc poudrage in both groups, reaching a plateau at 24 h, although in successful pleurodesis this response was significantly higher. DD dropped markedly at 24 h in the group with the successful outcome, but it did not show significant changes in the other group. A cut-off value of 61% for neutrophils and 61 mg·L<sup>−1</sup> for the DD at 24 h yielded the best prognosis for successful pleurodesis. The current authors conclude that serial measurements of neutrophil and d-dimer values into the pleural fluid after talc poudrage could be used as predictors of the outcome of pleurodesis.
Placebo-controlled, double-blind, cross-over trial of growth hormone treatment in prepubertal children with chronic renal failure
Authors: A.C.S. Hokken-Koelega, S.M.P.F. de Muinck Keizer-Schrama, S.L.S. Drop, E.D. Wolff, T. Stijnen, A. Bot, J.M. Wit, R.A. Donckerwolcke, M.C.J.W. de Jong, N.C.B. Abbad, W.F. Blum
Journal: The Lancet (1991)
Clinical value of the metabolic syndrome for long term prediction of total and cardiovascular mortality: prospective, population based cohort study
Authors: Johan Sundström, Ulf Risérus, Liisa Byberg, Björn Zethelius, Hans Lithell, Lars Lind
Journal: BMJ (2006)

To find out if the presence of the metabolic syndrome increases the risk of subsequent total and cardiovascular mortality, taking into account established risk factors for cardiovascular disease.Prospective cohort study.General population.A community based sample of 2322 men followed since 1970 for a maximum of 32.7 years, investigated at ages 50 and 70.The relations of the metabolic syndrome defined by the national cholesterol education programme (NCEP) of the US National Heart, Lung, and Blood Institute or criteria of the World Health Organization (WHO) to subsequent total and cardiovascular mortality.When adding the metabolic syndrome to models with established risk factors for cardiovascular disease (smoking, diabetes, hypertension, and serum cholesterol) at age 50, presence of the metabolic syndrome as defined in the NCEP significantly predicted total and cardiovascular mortality (Cox proportional hazard ratios 1.36, 95% confidence interval 1.17 to 1.58; and 1.59, 1.29 to 1.95, respectively). The metabolic syndrome added prognostic information to that of the established risk factors for cardiovascular disease (likelihood ratio tests, P < 0.0001 for both outcomes). Similar results were obtained in a subsample without diabetes or manifest cardiovascular disease.In a large, community based sample of middle aged men, the presence of the metabolic syndrome according to the definition of the NCEP gave long term prognostic information regarding total and cardiovascular mortality if the status of established risk factors for cardiovascular disease was known. If confirmed this may indicate clinical value in diagnosing the metabolic syndrome.