tbuckley/cabot-search huggingface dataset:
Role of obesity in GORD-related disorders
Authors: H. El-Serag
Journal: Gut (2008)

Obesity satisfies several criteria for a causal association with GORD and its complications including generally consistent association and some dose–response relationship. Abdominal obesity seems to explain a considerable part of this association operating mostly by increasing intragastric pressure, gastroesophageal gradient, TLOSR, and oesophageal acid exposure. Additional humoral mechanisms may be important in Barrett's oesophagus and oesophageal adenocarcinoma but this remains poorly examined. Maintaining normal weight may reduce the likelihood of developing GORD and its potential complications.
Epithelial versus Mesenchymal Phenotype Determines <i>In vitro</i> Sensitivity and Predicts Clinical Activity of Erlotinib in Lung Cancer Patients
Authors: Robert L. Yauch, Thomas Januario, David A. Eberhard, Guy Cavet, Wenjing Zhu, Ling Fu, Thinh Q. Pham, Robert Soriano, Jeremy Stinson, Somasekar Seshagiri, Zora Modrusan, Chin-Yu Lin, Vincent O'Neill, Lukas C. Amler
Journal: Clinical Cancer Research (2005)

Abstract Significant improvements in the outcome of non–small cell lung carcinoma (NSCLC) have been reported in patients treated with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. To discover biomarkers for the enrichment of patients who might benefit from treatment, a pharmacogenomic approach was used to identify gene signatures that may predict erlotinib activity using in vitro model systems. Erlotinib sensitivity in a panel of 42 NSCLC cell lines was determined by EGFR-mediated proliferative potential, EGFR mutations, and/or EGFR gene amplification, thus supporting an underlying biological mechanism of receptor activation. A strong multigene signature indicative of an epithelial to mesenchymal transition (EMT) was identified as a determinant of insensitivity to erlotinib through both supervised and unsupervised gene expression approaches. This observation was further supported by expression analysis of classic EMT marker proteins, including E-cadherin and vimentin. To investigate the clinical relevance of these findings, we examined expression of the epithelial marker E-cadherin by immunohistochemistry on primary tumor samples from subjects enrolled in a randomized NSCLC clinical trial in which erlotinib in combination with chemotherapy previously failed to show clinical activity. The majority (75%) of the 87 subjects tested showed strong E-cadherin staining and exhibited a significantly longer time to progression (hazard ratio, 0.37; log rank P = 0.0028) and a nonsignificant trend toward longer survival with erlotinib plus chemotherapy treatment versus chemotherapy alone. These data support a potential role for EMT as a determinant of EGFR activity in NSCLC tumor cells and E-cadherin expression as a novel biomarker predicting clinical activity of the EGFR inhibitor erlotinib in NSCLC patients.
Adhesion of Memory Lymphocytes to Vascular Cell Adhesion Molecule-1–Transduced Human Vascular Endothelial Cells Under Simulated Physiological Flow Conditions In Vitro
Authors: Robert E. Gerszten, Francis W. Luscinskas, Han T. Ding, David A. Dichek, Lloyd M. Stoolman, Michael A. Gimbrone, Anthony Rosenzweig
Journal: Circulation Research (1996)

The accumulation of mononuclear leukocytes is an early and persistent finding in atherosclerotic plaques. These mononuclear leukocytes are mostly monocyte-derived, but up to 20% are lymphocytes, predominantly CD4 + CD45RO + (memory) T cells. To evaluate the potential of adenovirus vectors for studies of mononuclear leukocyte recruitment in vitro, we studied the effects of adenovirus vectors per se on human umbilical vein endothelial cells (HUVECs), a well-characterized in vitro model of vascular endothelium. A recombinant adenovirus containing the seven-domain isoform of rabbit vascular cell adhesion molecule-1 (rVCAM-1) was constructed and used to study lymphocyte adhesion under defined laminar flow conditions in transduced HUVEC monolayers. No increase in basal HUVEC surface expression of the inducible endothelial adhesion molecules and markers of activation, E-selectin and VCAM-1, was noted across a broad range of multiplicity of infection. A modest dose-dependent increase in surface intercellular adhesion molecule-1 expression was detectable by flow cytometry at an MOI of &gt;30 plaque-forming units per cell. Under defined laminar flow from 1.5 to 0.5 dyne/cm 2 , the adenovirus vector carrying rVCAM-1 mediated stable adhesion of both a Jurkat T-cell line and primary human CD4 + CD45RO + (memory) T cells. Monoclonal antibodies to α 4 -integrin or rVCAM-1 abolished adhesion, whereas monoclonal antibodies to CD18 or P-selectin had no effect. We conclude that adenoviral gene transfer is useful for studies of VCAM-1–dependent leukocyte adhesion in vitro and that endothelial expression of VCAM-1 alone, in the absence of overt endothelial cell activation, is sufficient under simulated physiological flow conditions to support adhesion of memory T cells, the predominant lymphocyte subset in atherosclerotic plaque.
Effects of a palatinose-based liquid diet (Inslow) on glycemic control and the second-meal effect in healthy men
Authors: Hidekazu Arai, Akira Mizuno, Masae Sakuma, Makiko Fukaya, Kaoru Matsuo, Kazusa Muto, Hajime Sasaki, Motoi Matsuura, Hisami Okumura, Hironori Yamamoto, Yutaka Taketani, Toshio Doi, Eiji Takeda
Journal: Metabolism (2006)
Local overexpression of C-type natriuretic peptide ameliorates vascular adaptation of porcine hemodialysis grafts
Authors: Joris I. Rotmans, Hence J.M. Verhagen, Evelyn Velema, Dominique P.V. de Kleijn, Mieke van den Heuvel, John J.P. Kastelein, Gerard Pasterkamp, Erik S.G. Stroes
Journal: Kidney International (2004)
Musings on the concept of exaptation and “creationism”
Authors: Charles Crawford
Journal: Behavioral and Brain Sciences (2002)

I claim that our desire to be special motivates us to suppose that if we were not God created, we must be self-created. I also claim that Stephen J Gould's claims about punctuated equilibrium, the absence of directional selection, and exaptations, when taken together, lead to kind of secular creationism. I introduce the notion of “adaptive effects” and argue that a focus on the actual physiological and psychological mechanisms that produce adaptations provides a way out of the exaptation dilemma.
Functionalized polymersomes with outlayered polyelectrolyte gels for potential tumor-targeted delivery of multimodal therapies and MR imaging
Authors: Wen-Hsuan Chiang, Wen-Chia Huang, Chien-Wen Chang, Ming-Yin Shen, Zong-Fu Shih, Yi-Fong Huang, Sung-Chyr Lin, Hsin-Cheng Chiu
Journal: Journal of Controlled Release (2013)
Intrapulmonary vascular shunt pathways in alveolar capillary dysplasia with misalignment of pulmonary veins
Authors: Csaba Galambos, Sunder Sims-Lucas, Noorjahan Ali, Jason Gien, Megan K Dishop, Steven H Abman
Journal: Thorax (2014)

<h3>Abstract</h3> Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a lethal neonatal lung disease characterised by severe pulmonary hypertension, abnormal vasculature and intractable hypoxaemia. Mechanisms linking abnormal lung vasculature with severe hypoxaemia in ACD/MPV are unknown. We investigated whether bronchopulmonary anastomoses form right-to-left shunt pathways in ACD/MVP. We studied 2 infants who died of ACD/MPV postmortem with direct injections of coloured ink into the pulmonary artery, bronchial artery and pulmonary veins. Extensive histological evaluations included serial sectioning, immunostaining and 3-dimensional reconstruction demonstrated striking intrapulmonary vascular pathways linking the systemic and pulmonary circulations that bypass the alveolar capillary bed. These data support the role of prominent right-to-left intrapulmonary vascular shunt pathways in the pathophysiology of ACD/MPV.
Impact of the Duration of Adjuvant Hormonal Therapy in Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy: A Secondary Analysis of RTOG 85-31
Authors: Luis Souhami, Kyounghwa Bae, Miljenko Pilepich, Howard Sandler
Journal: Journal of Clinical Oncology (2009)

Radiation Therapy Oncology Group 85-31 was a randomized trial of androgen suppression for life for patients with locally advanced prostate cancer. However, not all patients continued on the protocol-mandated long-term hormonal therapy despite no evidence of recurrence. We correlated duration of adjuvant hormonal therapy and outcomes among patients who prematurely discontinued hormonal therapy.The protocol mandated pelvic radiotherapy followed by goserelin given indefinitely or until disease progression. There were 189 analyzable patients. Patients were divided in groups based on the tertile of hormonal therapy duration (HTD) as follows: < or = 1 year, more than 1 year and < or = 5 years, and more than 5 years. Overall survival (OS), disease-free survival (DFS), cause-specific mortality, local failure (LF), and distant metastasis (DM) were studied. Kaplan-Meier estimation and Cox proportional hazards regression model were used for OS and DFS, and Fine and Gray's regression model was used for the other outcomes.The median follow-up for surviving patients is 9.6 years. The median duration of adjuvant hormonal therapy was 2.2 years. The HTD more than 5 years group is significantly associated with an improved survival and DFS and fewer DMs than other HTD groups. After adjustment for age, radical prostatectomy, nodal status, Gleason score, and stage variables, the HTD more than 5 years group remains significantly associated with better OS and DFS than other HTD groups.In this hypothesis-generating analysis, prolonged HTD of more than 5 years seems significantly associated with improvements in most outcomes. Given these data, decreasing HTD to < or = 5 years may have a detrimental effect on patients with locally advanced prostate cancer. Only a randomized trial will conclusively clarify this issue.
Contribution of host, bacterial factors and antibiotic treatment to mortality in adult patients with bacteraemic pneumococcal pneumonia
Authors: Pontus Naucler, Jessica Darenberg, Eva Morfeldt, Åke Örtqvist, Birgitta Henriques Normark
Journal: Thorax (2013)

<h3>Rationale</h3> Host and bacterial factors as well as different treatment regimens are likely to influence the outcome in patients with bacteraemic pneumococcal pneumonia. <h3>Objectives</h3> To estimate the relative contribution of host factors as well as bacterial factors and antibiotic treatment to mortality in bacteraemic pneumococcal pneumonia. <h3>Methods</h3> A cohort study of 1580 adult patients with community-acquired bacteraemic pneumococcal pneumonia was conducted between 2007 and 2009 in Sweden. Data on host factors and initial antibiotic treatment were collected from patient records. Antibiotic resistance and serotype were determined for bacterial isolates. Logistic regression analyses were performed to assess risk factors for 30-day mortality. <h3>Results</h3> Smoking, alcohol abuse, solid tumour, liver disease and renal disease attributed to 14.9%, 13.1%, 13.1%, 8.0% and 7.4% of the mortality, respectively. Age was the strongest predictor, and mortality increased exponentially from 1.3% in patients &lt;45 years of age to 26.1% in patients aged ≥85 years. There was considerable confounding by host factors on the association between serotype and mortality. Increasing age, liver disease and serotype were associated with mortality in patients admitted to the ICU. Combined treatment with β-lactam antibiotics and macrolide/quinolone was associated with reduced mortality in patients in the ICU, although confounding could not be ruled out. <h3>Conclusions</h3> Host factors appear to be more important than the specific serotype as determinants of mortality in patients with bacteraemic pneumococcal pneumonia. Several host factors were identified that contribute to mortality, which is important for prognosis and to guide targeted prevention strategies.
Anxiety-Related Reactions Associated With Magnetic Resonance Imaging Examinations
Authors: J. Carlos Meléndez
Journal: JAMA (1993)

<h3>Objective.</h3> —To review the epidemiology of anxiety-related reactions during magnetic resonance imaging (MRI) examinations, the feasibility of identifying patients at risk, and the management strategies that have been applied. <h3>Data Sources.</h3> —Published original articles were retrieved using computerized MEDLINE searches encompassing 1980 through April 1993. Further references were obtained from the primary sources. <h3>Study Selection and Data Extraction.</h3> —All studies obtained through the data search were chosen for review. All data relevant to anxiety-related reactions were analyzed. <h3>Data Synthesis.</h3> —Anxiety-related reactions occur in approximately 4% to 30% of patients undergoing MRI, ranging from apprehension to severe reactions that interfere with the performance of the test. Criteria for diagnosis or categorization of the reactions and identification of patients at risk are scanty. Several management strategies have been proposed, including patient education, drug therapy, and cognitive-behavioral intervention. <h3>Conclusions.</h3> —While a more precise characterization of the nature and incidence of anxiety-related reactions during MRI examinations and better methods of recognizing patients at risk are desirable, a strategy for general and individual prophylaxis, identification of patients at risk, and individual patient management can be developed on the basis of current knowledge. (<i>JAMA</i>. 1993;270:745-747)
Consistent Deregulation of Gene Expression between Human and Murine <i>MLL</i> Rearrangement Leukemias
Authors: Zejuan Li, Roger T. Luo, Shuangli Mi, Miao Sun, Ping Chen, Jingyue Bao, Mary Beth Neilly, Nimanthi Jayathilaka, Deborah S. Johnson, Lili Wang, Catherine Lavau, Yanming Zhang, Charles Tseng, Xiuqing Zhang, Jian Wang, Jun Yu, Huanming Yang, San Ming Wang, Janet D. Rowley, Jianjun Chen, Michael J. Thirman
Journal: Cancer Research (2009)

Important biological and pathologic properties are often conserved across species. Although several mouse leukemia models have been well established, the genes deregulated in both human and murine leukemia cells have not been studied systematically. We performed a serial analysis of gene expression in both human and murine MLL-ELL or MLL-ENL leukemia cells and identified 88 genes that seemed to be significantly deregulated in both types of leukemia cells, including 57 genes not reported previously as being deregulated in MLL-associated leukemias. These changes were validated by quantitative PCR. The most up-regulated genes include several HOX genes (e.g., HOX A5, HOXA9, and HOXA10) and MEIS1, which are the typical hallmark of MLL rearrangement leukemia. The most down-regulated genes include LTF, LCN2, MMP9, S100A8, S100A9, PADI4, TGFBI, and CYBB. Notably, the up-regulated genes are enriched in gene ontology terms, such as gene expression and transcription, whereas the down-regulated genes are enriched in signal transduction and apoptosis. We showed that the CpG islands of the down-regulated genes are hypermethylated. We also showed that seven individual microRNAs (miRNA) from the mir-17-92 cluster, which are overexpressed in human MLL rearrangement leukemias, are also consistently overexpressed in mouse MLL rearrangement leukemia cells. Nineteen possible targets of these miRNAs were identified, and two of them (i.e., APP and RASSF2) were confirmed further by luciferase reporter and mutagenesis assays. The identification and validation of consistent changes of gene expression in human and murine MLL rearrangement leukemias provide important insights into the genetic base for MLL-associated leukemogenesis.
Role of N-acetyltransferase polymorphisms in hepatitis B related hepatocellular carcinoma: impact of smoking on risk
Authors: M-W Yu
Journal: Gut (2000)

<h3>BACKGROUND</h3> Persistent infection with hepatitis B virus (HBV) causes chronic phasic necroinflammation and regenerative proliferation in the liver. The sustained hepatocellular proliferation may render chronic HBV carriers more susceptible to the effects of environmental carcinogens. Aromatic amines are potential hepatocarcinogens in humans.<i>N</i>-acetyltransferase (NAT) is involved in the metabolic activation and detoxification of these compounds. <h3>AIMS</h3> To investigate if genetic polymorphisms in <i>N</i>-acetylation are related to hepatocellular carcinoma (HCC) among chronic HBV carriers. <h3>METHODS</h3> Genotyping of<i>NAT1</i> and <i>NAT2</i> was performed using polymerase chain reaction-restriction fragment length polymorphism on peripheral leucocyte DNA from 151 incident cases of HCC and 211 controls. All subjects were male, and were chronic HBV surface antigen carriers. <h3>RESULTS</h3> A significant association between <i>NAT2</i> genetic polymorphism and HCC was observed among chronic HBV carriers who were smokers but not among those who were non-smokers. For smoking HBV carriers, the odds ratios of developing HCC for those heterozygous and homozygous for the <i>NAT2*4</i> functional allele compared with those without any copies of the functional allele (reference group) were 2.67 (95% confidence interval 1.15–6.22) and 2.58 (95% confidence interval 1.04–6.43), respectively. The interaction between cigarette smoking and the presence of the<i>NAT2*4</i> allele just failed to reach statistical significance (p=0.06). No association between<i>NAT1</i> genotype and HCC was evident overall or within the smoking stratified subgroups. <h3>CONCLUSIONS</h3> Our results suggest that NAT2 activity may be particularly critical in smoking related hepatocarcinogenesis among chronic HBV carriers. Our data also indirectly support a role for tobacco smoke derived aromatic amines in the aetiology of HCC.
Isometric contractions in cardiac Purkyne fibres: characteristics in Na free Sr Tyrode
Authors: F. Verdonck, E. Carmeliet
Journal: Cardiovascular Research (1971)

Journal Article Isometric contractions in cardiac Purkyně fibres: characteristics in Na free Sr Tyrode Get access F. Verdonck, F. Verdonck From the Laboratorium voor Fysiologie Utiiuersiteit Leirveti, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Carmeliet E. Carmeliet From the Laboratorium voor Fysiologie Utiiuersiteit Leirveti, Belgium Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue supp1, July 1971, Pages 76–83, https://doi.org/10.1093/cvr/5.supp1.76 Published: 01 July 1971
High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma
Authors: A. Raso, S. Mascelli, R. Biassoni, P. Nozza, M. Kool, A. Pistorio, E. Ugolotti, C. Milanaccio, S. Pignatelli, M. Ferraro, M. Pavanello, M. Ravegnani, A. Cama, M. L. Garre, V. Capra
Journal: Neuro-Oncology (2011)

The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative– polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P= .007) and in those with metastasis (P= .03). Kaplan–Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P= .0004 and P= .002, for OS and PFS for all cases, respectively; P= .002 and P= .008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P= .008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P= .019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting.
A child with chronic manganese exposure from drinking water.
Authors: Alan Woolf, Robert Wright, Chitra Amarasiriwardena, David Bellinger
Journal: Environmental Health Perspectives (2002)

The patient's family bought a home in a suburb, but the proximity of the house to wetlands and its distance from the town water main prohibited connecting the house to town water. The family had a well drilled and they drank the well water for 5 years, despite the fact that the water was turbid, had a metallic taste, and left an orange-brown residue on clothes, dishes, and appliances. When the water was tested after 5 years of residential use, the manganese concentration was elevated (1.21 ppm; U.S. Environmental Protection Agency reference, < 0.05 ppm). The family's 10-year-old son had elevated manganese concentrations in whole blood, urine, and hair. The blood manganese level of his brother was normal, but his hair manganese level was elevated. The patient, the 10-year-old, was in the fifth grade and had no history of learning problems; however, teachers had noticed his inattentiveness and lack of focus in the classroom. Our results of cognitive testing were normal, but tests of memory revealed a markedly below-average performance: the patient's general memory index was at the 13th percentile, his verbal memory at the 19th percentile, his visual memory at the 14th percentile, and his learning index at the 19th percentile. The patient's free recall and cued recall tests were all 0.5-1.5 standard deviations (1 SD = 16th percentile) below normal. Psychometric testing scores showed normal IQ but unexpectedly poor verbal and visual memory. These findings are consistent with the known toxic effects of manganese, although a causal relationship cannot necessarily be inferred.
Reshaping the NHS workforce
Authors: L. Doyal
Journal: BMJ (2000)

Education and debate p 1067 

The staffing problems of the NHS continue to make headlines.1 Junior doctors are threatening to strike, consultants are voicing their frustration, and nurses are voting with their feet.2 Though their concerns are less visible, physiotherapists, radiographers, occupational therapists and other members of the professions allied to medicine are also facing major challenges.3 The problems have been well rehearsed but solutions seem as far away as ever.If the healthcare needs of this new millennium are to be met, more radical approaches to collaborative working will need to be explored.

By its very nature the healthcare labour force is an interdependent one. The different occupational groups did not develop in isolation from each other but as part of a complex and interdependent system capable of carrying out the many activities that make up a modern health service. Yet despite this obvious reciprocity, the different elements of the NHS labour force are still planned and managed in isolation. This continuing fragmentation has a major impact on the quality of patient care and on the wellbeing of health workers themselves.4

Since the 1970s there have been irresistible pressures towards collaborative working across traditional boundaries. More health workers are now organised into multiprofessional teams, and many nurses and those in the professions allied to medicine …