tbuckley/cabot-search huggingface dataset:
Low Counts Of Natural Killer Cells CD56 bright CD16 negative After Engraftment Are Associated With Worse Survival In Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Matheus Vescovi Gonçalves, Mihoko Yamamoto, Eliza Y. S. Kimura, Vergilio Antonio Renzi Colturato, Maura Valerio Ikoma, Marcos Mauad, Mair Pedro de Souza, Paulo Guilherme Alvarenga Gomes de Oliveira, Thiago Xavier Carneiro, Fabio R. Kerbauy, Nelson Hamerschlak, Yana Novis, Valeria Cortez Ginani, Adriana Seber, Vanderson Rocha, Alberto Orfao, Celso Arrais Rodrigues
Journal: Blood (2013)
Effect of gastric acid suppressants on human gastric motility Reply
Authors: M BORTOLOTTI, H P PARKMAN, R S FISHER
Journal: Gut (1999)

Phospholipase A 2 and acute pancreatitis in rats EDITOR,-Phospholipase A 2 (PLA 2 ) is an enzyme that cleaves fatty acids from phospholipids, leading to the generation of inflammatory eicosanoids. 1 The group II isoenzyme of phospholipase A 2 (PLA 2 -II) is raised in peripheral blood during various inflammatory states. 2 PLA 2 is induced in vitro and in vivo by the classic acute phase cytokine interleukin 6. 3 4 Therefore PLA 2 -II can be regarded as an acute phase protein.With great interest we read the well designed study of Furue et al (Gut 1997;41:826-31) who could clearly show that most PLA 2 activity during sodium deoxycholate induced acute pancreatitis in rats is due to the group II isoenzyme.Furue and colleagues suggested that the liver is the main source of this enzyme in their experiments because Nevalainen and coworkers 5 and Crowl and coworkers 3 described PLA 2 -II activity in human hepatocytes.We agree with the suggestion of Furue et al that PLA 2 -II is produced in human hepatocytes like classic acute phase proteins.This was also demonstrated by our group, 6 but we think that the extrapolation of these findings from human tissue to animal experiments, as done by Furue et al, requires some clarification.Hatch et al were able to show that liver macrophages and not hepatocytes were the main source of PLA 2 -II in rats during endotoxin induced acute phase reaction. 7As a consequence, liver macrophages but not hepatocytes could also be the main source of PLA 2 -II in the animal experiments presented by Furue and collaborators.Therefore an alternative pathogenetic mechanism leading to liver damage in experimental induced acute pancreatitis should be taken into account.Our alternative pathogenetic sequence is that PLA 2 -II released by liver macrophages attacks adjacent already damaged liver tissue, thus leading to complete destruction of hepatocytes with subsequent release of aminotransferases into the circulation, as shown by Furue et al.In conclusion, we agree that PLA 2 -II could be an important mediator of liver failure in acute pancreatitis, but alternative pathomechanisms resulting from diVerent production sites should be discussed.
FAK/PI3K activation controls actin reorganization and cell motility
Authors: S. Agelaki, G. Kallergi, Ch. Markomanolaki, V. Georgoulias, Ch. Stournaras
Journal: Cancer Research (2007)

3035  Focal Adhesion kinase (FAK) localized in focal adhesions influences the dynamic equilibrium of actin cytoskeleton (AC) regulating cell motility and invasion. We have recently identified a novel, specific signalling pathway regulating actin cytoskeleton dynamics and cell motility in malignant breast and prostate human epithelial cells. Incubation of MCF7 breast cancer cells with the opioid agonist αs1 casomorphin and LNCaP prostate cells with testosterone-BSA (testo-BSA) stimulated actin reorganization. This was associated with FAK phosphorylation and subsequent phosphatidylinositol-3 kinase (PI-3K) and Rac1 activation. In the present study we first investigated whether the FAK/PI-3K pathway operates in MCF-7 cells upon treatment with a different stimulus. Since membrane androgen receptors have also been identified in breast cancer cells we investigated the effect of testo-BSA on MCF7 cell line. Immunofluorescence microscopy with testo-BSA FITC confirmed the presence of membrane androgen receptors in MCF7 cells. Treatment with testo-BSA resulted in early actin reorganization associated with rapid FAK and PI3K activation. To test whether actin rearrangement affects cell motility wound healing assay was performed demonstrating a significant inhibition of wound closure. We next investigated the functional role of the FAK/PI-3K-actin signalling pathway in cells of different origin, the A375 melanoma cell line. Incubation with αs1 casomorphin for 15 min to up to 24 h resulted in early significant actin reorganization. In line with this, morphological analysis showed increased number of lamelipodia and stress fibers equally distributed to the cytoplasm. Casomorphin also induced significant early phosphorylation of FAK and PI-3K. FAK phosphorylation was still evident in cells pretreated with the PI-3K inhibitor wortmanin, indicating that FAK activation occurs upstream of PI-3K. Affinity precipitation with a GST-fusion protein corresponding to the p21-binding domain of PAK1 performed in cell lysates confirmed Rac-1 activation. Wound healing assay revealed that casomorphin significantly inhibited cell motility. In conclusion, actin reorganization through FAK and subsequent PI3-K/Rac-1 activation operates in various human cancer cell systems supporting a broader role for FAK in controlling cell motility and underlines the importance of FAK as a new therapeutic target in cancer.
Abstract P1-03-04: The impact of Angelina Jolie (AJ)'s story on genetic referral and testing at an academic cancer centre
Authors: Jacques Raphael, Sunil Verma, Paul Hewitt, Andrea Eisen
Journal: Cancer Research (2015)

Abstract Introduction/background In May 2013, AJ revealed to the media that she had undergone preventive double mastectomy. The actress had a family history of breast and ovarian cancer and tested positive for the BRCA1 gene mutation. Media coverage has been extensive, but it’s not clear what messages the public and professional medical staff took from this personal story that sometimes could be misleading. Methods We conducted a retrospective review in our centre using data from the clinical database of the Familial Cancer Program in a tertiary care cancer centre. The impact of AJ’s story on genetic counseling referrals was assessed by comparing the number of referrals made 6 months before and after the story. In addition, the quality of referrals was reported by comparing the number of patients who qualified for genetic testing as defined by the Ontario Ministry of Health and Long Term Care and the ones who carried a BRCA1/2 mutation before and after the media release. Results The number of women referred for genetic counseling increased by 85% after the release of AJ’s story (479 before versus 887 after). This translated to an increase of 99% in the number of women who qualified for a genetic testing (211 before versus 419 after). Among them, 120 and 254 women had a history of breast and ovarian cancer in their family, 16 and 37 women had a history of male breast cancer in their family and 28 and 15 women were diagnosed with breast cancer at the age of 35 or less before and after AJ’s story respectively. Furthermore, the number of BRCA1/2 carriers identified increased by 107% (29 (14 BRCA1, 15 BRCA2) before and 60 (32 BRCA1, 28 BRCA2) after). Conclusion This study clearly shows that the number of genetic referrals doubled after AJ’s story. Nevertheless, the quality of referral remained the same with nearly the same percentage of patients who qualified for genetic testing and who were identified as BRCA1/2 carriers. The challenge is to meet the increased demand for cancer genetic services including screening, counseling, testing, and preventive surgery. After AJ’s story the current model of genetic counseling may need to be revisited. Key words: Angelina Jolie; BRCA1/2; genetic referral; genetic counseling; genetic testing. Citation Format: Jacques Raphael, Sunil Verma, Paul Hewitt, Andrea Eisen. The impact of Angelina Jolie (AJ)'s story on genetic referral and testing at an academic cancer centre [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-03-04.
S13 Differentiated human rhinovirus loads in stable COPD and at exacerbation
Authors: S. N. George, A. J. Mackay, A. R. C. Patel, R. J. Sapsford, D. S. Garcha, G. C. Donaldson, J. A. Wedzicha
Journal: Thorax (2011)

<h3>Introduction</h3> Human rhinoviruses (HRV) are the main aetiological agents of virus-associated COPD exacerbations (Seemungal <i>et al</i>, 2001). However the importance of the level of viral load as a trigger for naturally occurring exacerbations is not fully understood. We aimed to assess and quantify HRV prevalence and load in stable and exacerbating patients from the London COPD cohort. <h3>Methods</h3> A real-time qPCR protocol was utilised to detect HRV presence and quantify load in sputum samples taken at baseline (n=58) and at COPD exacerbation onset (n=57). COPD patients were defined as stable if exacerbation-free for at least 42 days since the previous exacerbation and more than 14 days before the next. Exacerbations were defined using our usual symptom criteria; an increase in respiratory symptoms for two consecutive days, with at least one symptom being a major symptom; dyspnoea, sputum purulence or volume and the other a major or minor symptom; wheeze, cold sore throat, and cough (Anthonisen criteria). A χ<sup>2</sup> test was used to compare HRV prevalence of the two disease phases, and an independent-samples t test was used to compare the differences in viral load. <h3>Results</h3> Sixty-four patients provided 115 sputum samples: mean age 70.5 years (SD±8.1); FEV<sub>1</sub> 45.8% predicted (±20.0%); current smoker 31.3%. There is a significantly higher prevalence of HRV at exacerbation onset, 31.6% (18/57) compared to baseline 15.5% (9/58) (p=0.042). Similarly, the mean viral load was significantly greater at exacerbation onset 1.70 (±1.67) log<sub>10</sub> pfu/ml than baseline 0.30 (±0.69) log<sub>10</sub> pfu/ml (p=0.025), exhibiting a 25-fold increase in viral load from baseline to exacerbation. 6.9% (4/58) of patients were positive for HRV at baseline only, 26.3% (15/57) at exacerbation only and 8.8% (4/45) at both time points (p=0.006). <h3>Conclusions</h3> HRV load is significantly greater at COPD exacerbation than when detected in the stable state. This emphasises the importance of HRV as a key trigger of COPD exacerbations. HRV can be detected in the stable state; however the loads are very low suggesting asymptomatic carriage rather than chronic infection.
Abstract 12097: Resting Supine Heart Rate and Risk of Incident Heart Failure and All-Cause Mortality in 5475 Community-Dwelling Older Adults During 13 Years of Follow-Up
Authors: Gerasimos S Filippatos, Yan Zhang, Gregg C Fonarow, Richard M Allman, Michael Bohm, Maria Anastasiou-Nana, Inmaculada B Aban, Ali Ahmed
Journal: Circulation (2011)

Background A high heart rate (HR) has been shown to be associated with poor outcomes in patients with heart failure (HF). However, the association of resting HR with outcomes in community-dwelling ...
The theme of death in complex partial seizures
Authors: D B Greenberg, F H Hochberg, G B Murray
Journal: American Journal of Psychiatry (1984)

The theme of death highlighted the depersonalization phenomena of four patients with complex partial seizures. These patients became preoccupied with death in association with psychomotor seizures, visual hallucinations, and altered perception of time and reality. The episodic sense of being dead or of having an appointment with death is a clue to the diagnosis of recurrent complex partial seizures even without overt motor stigmata of seizures. The syndrome differs from fear of death, steroid psychosis, the "near death syndrome," and Cotard's syndrome. Adjustment of antiseizure medication is an important therapeutic maneuver.
Laser fabricated discontinuous anisotropic microconical substrates as a new model scaffold to control the directionality of neuronal network outgrowth
Authors: C. Simitzi, P. Efstathopoulos, A. Kourgiantaki, A. Ranella, I. Charalampopoulos, C. Fotakis, I. Athanassakis, E. Stratakis, A. Gravanis
Journal: Biomaterials (2015)
Abstract 18309: Wireless Electrocardiographic Transmission with e-Activation of PCI Team and Reconstructed System of Care Shortens Door-to-Balloon Time in Acute Myocardial Infarction
Authors: Wei-Tien Chang, Chee-Ming Lee, Li-Chin Chen, Chih-Hung Wang, Chiao-Hao Lee, Bey-Jing Yang, Li-Fen Yang, Chuen-Den Tseng, Jiunn-Lee Lin, Shyr-Chyr Chen, Kuan-Yu Hung, Ming-Fong Chen
Journal: Circulation (2011)

Background: Early reperfusion of the occluded coronary artery is the first priority in the treatment of acute ST-elevation myocardial infarction (STEMI). Time to primary percutaneous coronary inter...
Profiling differentially secreted biomarkers in the MCF10 isogenic breast cancer cell lines for biomarker discovery
Authors: Lewis Pannell, Brandon Metge, Flaubert Mbeunkui, Lalita Shevde
Journal: Cancer Research (2007)

607   Secreted proteins (the secretome) have high potential use as sources of biomarkers of cancer. An optimized method for isolating the secreted proteome of an isogenic series of breast cancer cell lines varying from the non-tumorigenic and non-metastatic MCF10A to the metastatic MCF10CA cl. d has been developed. Cells are grown in serum free media which is harvested and partially fractionated using a tC2 SepPak cartridge. The fractions are then digested and analyzed using LC-MS/MS (peptide sequence based analyses). Repeatable protein profiles were obtained from 3 separate preparations of each cell line, and from duplicate analyses of the same line. The combined data from all fractions and analyses of each cell line were searched against the NCBI reference sequence database using a Mascot search engine. There were significant changes observed between the secreted proteomes of the cell lines. The most significant changes occurred with alpha-1-antichymotrypsin and galectin-3-binding protein which were highly secreted from the MCF10 DCIS.com and MCF10A cl. d, but undetected in MCF10A and MCF10AT cell lines. These proteins were also secreted from unrelated metastatic cell lines in our earlier research (Mbeunkui,  et al. , J. Prot. Res. 2006, 5, 899-906). Other proteins showing increasing abundance in the more aggressive cell lines included alpha-1-antitrypsin, cathepsin D and quiescin Q6. The S100 proteins, associated with aggressive cancers, showed variable changes in abundance. Secretion of proteins often believed to be strictly cytosolic, such as annexin A2, was observed. These proteins are all predicted to undergo non-classical secretion (SecretomeIP, Center for Biological Sequence Analysis). The results were validated for five selected proteins by western blot analysis. The comparison of the secretome of an isogenic series of cell lines reveals proteins related to cancer aggressiveness/progression, and proteins which are potentially highly specific markers for the early detection of cancer.  This research was partially supported by grants from the National Cancer Institute (5R21CA116070 to LKP) and the Susan G. Komen Breast Cancer Foundation (BCTR0402317 to LAS).
What are the causes?
Authors: James N Hardy
Journal: BMJ (2007)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive after our selection. DeciDing on caesarean section Vaginal birth after a caesarean is not always beneficialThe study by Montgomery et al and the accompanying editorial are based on the premise that vaginal delivery after one caesarean section is necessarily a beneficial and desirable objective or outcome. 1 2 However, the box shows the risks and benefits as published in the recent RCOG (Royal College of Obstetricians and Gynaecologists) guidelines. 3 Given that most women in developed countries are unlikely to have more than two to three babies, the value of promoting vaginal delivery after one caesarean section is highly questionable.Women with a breech presentation are no longer offered a choice between vaginal delivery and caesarean section on the basis of the results of the term breech trial. 4 Must we wait for such a trial to recognise that vaginal delivery after one caesarean section costs lives and caesarean section saves lives?Women should have a choice, but this should not come before safety.To promote a process that is known to be associated with greater mortality and morbidity, or consider such a process as beneficial or desirable seems inappropriate irrespective of the reduction in women's anxiety.
乳腺疾病基础知识（二）早期乳腺癌的内科治疗（II）：内分泌治疗
Authors: lan, Smith, Susan, Chua, 赵卫红（译）, 徐兵河（校）
Journal: BMJ (2006)

选择乳腺癌辅助治疗时需要考虑的因素有：复发的风险、不同治疗方法的潜在获益、雌激素受体的状态、患者的年龄和患者对治疗的接受能力。复发风险与目前已知的预后因素有关，这些预后因素可以预测哪些患者属于高危复发风险组。年龄和月经状态是影响辅助治疗选择的重要因素。
Evaluation Of Anemia After Long-Term Treatment With Imatinib In Chronic Myeloid Leukemia In Chronic Phase
Authors: Muriel Silva Moura, Katia B. Pagnano, Thais Benevides, Carmino A De Souza, Irene Lorand-Metze, Marcia T Delamain, Gislaine O. Duarte, Fernando V Pericole, Priscila Percout, Maria Dias, Bruno Duarte, Paula Campos, Paola Assunção, Luciene Oliveira, Pamela Paul, Eliana Fernandes
Journal: Blood (2013)
Alarm Sounded on Fake, Tainted Drugs
Authors: Brian Vastag
Journal: JAMA (2003)

IT IS ONE HORROR STORY OF MANY: A father injects his son with human growth hormone, then discovers after the child complains of burning that the vials contain inexpensive insulin. Investigators traced the vials, which the father had purchased at a pharmacy in Orlando, Fla, to a large wholesaler. That wholesaler had acquired the ostensible growth hormone only after the shipment had been handled by three smaller distributors. The originating company in this dangerous chain held no valid license, but because it had claimed to be an authorized distributor—that is, one that receives batches of pharmaceuticals directly from the manufacturer—it was under no obligation to identify the source of the drug. According to a Florida grand jury, investigators uncovered all this in “a matter of minutes.” The young boy whose experience triggered the investigation recovered, but the dangerous and growing problem of shady secondary drug wholesalers remains. Although the 7000 secondary distributors in the United States traffic only a tiny percentage of all US pharmaceuticals, drug regulators and industry experts are nearly unanimous in declaring them the weakest link in a potentially deadly chain.
腹痛-反酸-呕吐
Authors: 李融融, 吴东, 杨红, 李景南
Journal: BMJ (2010)

患者男,61岁,反复上腹痛40余年,剑突下烧灼感,反酸,呕吐胃内容物. 慢性上腹痛病因很多,包括消化性溃疡、胆石症、慢性胰腺炎、横结肠疾病、肠系膜血管病变等,偶尔也可见于心肺及胸膜疾病.患者病程漫长,似乎是一个良性经过,但应注意询问病史,近期病情若有新的变化,亦不排除恶性病变,例如长期胃溃疡继发胃癌、慢性胰腺炎引起胰腺癌等.详细了解腹痛特点有助于鉴别诊断。
新生儿喉喘鸣-婴儿反复患喘息性支气管炎-肺动脉吊带
Authors: 袁红梅, 张红, 吴明昌
Journal: BMJ (2010)

患儿男,第1胎第1产,足月顺产,无出生窒息,体重2500 g,羊水正常.母孕7个月时曾患感冒,孕期超声检查胎儿未见异常.生后体检正常,无青紫,心脏无杂音.第3天常规彩色多普勒超声心动图(彩超)检查提示卵圆孔未闭1.6 mm,各房室内径大小正常,各房室瓣形态结构未见异常,肺动脉分支显示不满意.生后1个月内呼吸时咽喉有呼噜声,活动与喂奶后更响.生后6周体检及7周因湿疹就诊时均疑有先天性喉喘鸣,嘱服钙剂.3个月复查心脏彩超示卵圆孔近闭合。
Abstract 17290: Prevalence of Free Methyl Chloride as an Impurity in Generic Clopidogrel Preparations. Safety Implications in Cardiovascular Patients
Authors: Rakesh Wahi, Gundu Rao, Indermohan Thethi, Lekha Pathak
Journal: Circulation (2010)

Various salts of clopidogrel are known to degrade by two main pathways including racemization and methyl ester hydrolysis. Methyl ester hydrolysis of hydrochloride salts of clopidogrel leads to the...
Predictors of Long-Term Response to High-Dose Interferon Therapy in Type II Cryoglobulinemia Associated With Hepatitis C Virus Infection
Authors: Milvia Casato, Vincent Agnello, Leopoldo P. Pucillo, Glenn B. Knight, Marco Leoni, Savino Del Vecchio, Cristina Mazzilli, Guido Antonelli, Lorenzo Bonomo
Journal: Blood (1997)
You have to put your finger in
Authors: Jeremy L Menage
Journal: BMJ (2008)

Leukocytes are rapidly recruited to sites of inflammation via interactions with the vascular endothelium. The steroid hormone dehydroepiandrosterone (DHEA) exerts anti-inflammatory properties; however, the underlying mechanisms are poorly understood. In this study, we show that an anti-inflammatory mechanism of DHEA involves the regulation of developmental endothelial locus 1 (DEL-1) expression. DEL-1 is a secreted homeostatic factor that inhibits β2-integrin–dependent leukocyte adhesion, and the subsequent leukocyte recruitment and its expression is downregulated upon inflammation. Similarly, DHEA inhibited leukocyte adhesion to the endothelium in venules of the inflamed mouse cremaster muscle. Importantly, in a model of lung inflammation, DHEA limited neutrophil recruitment in a DEL-1–dependent manner. Mechanistically, DHEA counteracted the inhibitory effect of inflammation on DEL-1 expression. Indeed, whereas TNF reduced DEL-1 expression and secretion in endothelial cells by diminishing C/EBPβ binding to the <i>DEL-1</i> gene promoter, DHEA counteracted the inhibitory effect of TNF via activation of tropomyosin receptor kinase A (TRKA) and downstream PI3K/AKT signaling that restored C/EBPβ binding to the <i>DEL-1</i> promoter. In conclusion, DHEA restrains neutrophil recruitment by reversing inflammation-induced downregulation of DEL-1 expression. Therefore, the anti-inflammatory DHEA/DEL-1 axis could be harnessed therapeutically in the context of inflammatory diseases.
Inhibition of p97 with the First-in-Class Small Molecule CB-5083: A Novel Strategy for Acute Myeloid Leukemia Therapy
Authors: Rita Tohme, Ronan Le Moigne, Bartlomiej P Przychodzen, Yingchun Han, Mark Rolfe, Hetty E. Carraway, Stevan Djakovic, Dan Anderson, David Wustrow, Han-Jie Zhou, Steve Wong, Kevin R. Kelly, Yogen Saunthararajah, Anjali S. Advani, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Steffan T. Nawrocki, Jennifer S. Carew
Journal: Blood (2014)
Abstract 19022: Intralipid Therapy for Prevention of Pulmonary Hypertension-induced Right Ventricular Failure
Authors: Soban Umar, Federica Maltese, Humann Matori, Andrea Iorga, Rangarajan D Nadadur, Parisa Partownavid, Siamak Rahman, Mansoureh Eghbali
Journal: Circulation (2010)

Introduction: Intralipid (ILP) is an effective treatment for local anesthetic-induced cardiac arrest and is widely used as parenteral nutrition for patients. Some of its constituents are known prec...
Absence of Linkage Between Type III Protein S Deficiency and the PROS1 and C4BP Genes in Families Carrying the Protein S Heerlen Allele
Authors: Yolanda Espinosa-Parrilla, Marta Morell, Joan Carles Souto, Montserrat Borrell, Damián Heine-Suñer, Isabel Tirado, Vı́ctor Volpini, Xavier Estivill, Núria Sala
Journal: Blood (1997)