tbuckley/cabot-search huggingface dataset:
Growth hormone, insulin, and prolactin secretion in anorexia nervosa and obesity during bromocriptine treatment.
Authors: A D Harrower, P L Yap, I M Nairn, H J Walton, J A Strong, A Craig
Journal: BMJ (1977)

We studied secretion of growth hormone (GH), insulin, and prolactin in eight women with anorexia nervosa and nine women with refractory obesity before and during treatment with bromocriptine, 10 mg/day. In the anorexic patients the raised plasma GH concentrations occurring during an oral glucose tolerance test fell significantly while on bromocriptine treatment, but there was no change in plasma insulin or blood glucose concentrations. In the obese patients, however, plasma GH concentrations remained low during the oral glucose tolerance test, and were not modified by bromocriptine. Blood glucose and plasma insulin concentrations were also unchanged. Plasma GH and plasma 11-hydroxycorticosteroid responses to insulin-induced hypoglycaemia were unaffected. Serum prolactin concentrations which were raised in five anorexic patients and marginally raised in two obese subjects, fell significantly in both groups during treatment. We observed no consistent weight changes in either groups.
Comparison of the effects of inotropic interventions on isometric tension and shortening in isolated ferret ventricular muscle
Authors: J. A LEE, D. G ALLEN
Journal: Cardiovascular Research (1989)

Journal Article Comparison of the effects of inotropic interventions on isometric tension and shortening in isolated ferret ventricular muscle Get access JOHN A LEE, JOHN A LEE From the Department of Physiology, University College London Address for correspondence and reprints: Dr J A Lee, Department of Physiology, University College London, Gower St, London WC1E 6BT. Search for other works by this author on: Oxford Academic PubMed Google Scholar DAVID G ALLEN DAVID G ALLEN From the Department of Physiology, University College London Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 23, Issue 9, September 1989, Pages 748–755, https://doi.org/10.1093/cvr/23.9.748 Published: 01 September 1989 Article history Accepted: 23 March 1989 Published: 01 September 1989
Abstract 4414: EC0531: A potent folate-targeted tubulysin conjugate
Authors: Christopher P. Leamon, Joseph A. Reddy, Yu Wang, Ryan Dorton, Elaine Westrick, Alicia Bloomfield, Marilynn Vetzel, Patrick J. Klein, Iontcho R. Vlahov
Journal: Cancer Research (2010)

Abstract Our lab is focused on the discovery and development of highly potent chemotherapeutic agents that target folate receptor (FR) expressing malignancies. One such compound, EC0305, represents a folate-tubulysin B construct capable of specifically eradicating well-established, FR-positive subcutaneous tumors from mice [Cancer Res (2008) 68:9839]. Recently, multiple polar carbohydrate segments (e.g. 1-amino-1-deoxy-glucitolyl–glutamate) were placed in-between the folate and tubulysin B moieties (i.e. the spacer region) of EC0305 to create a new compound with more desirable biological properties. When tested in culture, this novel agent, herein referred to as EC0531, was found to specifically inhibit the growth of FR-positive cells (IC50 of ∼ 2 nM) in a dose-dependent manner. Its cytotoxic activity was blocked in the presence of an excess of folic acid, and no activity was observed against FR-negative cells, thereby demonstrating this compound's target specificity. EC0531′s potency was confirmed againstin a human KB xenograft-nu/nu mice cancer model. Here, EC0531 therapy displayed remarkable anti-tumor activity (5/5 cures) with dose levels that did not cause weight loss or major organ tissue degeneration. In contrast, the anti-tumor activity was completely abolished (0/5 remissions) in EC0531-treated animals that were co-dosed with a benign folate-containing analog. The advantage provided by folate conjugation was further proven by the un-targeted free drug, which was found to be completely inactive (0/5 remissions) at both tolerable and highly toxic dose levels. Collectively, these results show that this potent anti-proliferative tubulysin compound can be specifically delivered to FR-positive tumors to provide substantial therapeutic benefit using well tolerated dosing regimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4414.
Where Are You From?
Authors: Kevin C. Katz, Sharon L. Walmsley, Anne G. McLeod, Jay S. Keystone, Allan S. Detsky
Journal: New England Journal of Medicine (2002)

A 52-year-old man with human immunodeficiency virus infection who had emigrated from Guyana 15 years earlier presents with fever. He has a long history of anemia and thrombocytopenia but no history of opportunistic infections.
The Etiology of Myocardial Infarction. Henry Ford Hospital International Symposium Held at the Hospital November 16, 17, 18, 1961
Authors: Sigmund L. Wilens
Journal: JAMA (1963)

The importance of this impressive volume is that it documents the wide flux in ideas that currently motivate a large group of investigators concerned with the nature of atherosclerosis and its most important clinical consequence, myocardial infarction. Each of the 38 brief dissertations compiled in this symposium is the product of carefully planned studies, expertly consummated, which yield an inspiring amount of intriguing new information. The net effect of the book, however, is very different. At times the investigators appear to prefer flanking maneuvers rather than direct assaults on the subject in hand. Much of the material presented is only remotely related to myocardial infarction. Some avant-gardists seem to be suffering from defective navigation. Hardly a plaque of any composition is left unturned. Genetic, meteorologic and emotional factors, intestinal flora, stress, thrombogenesis, a brood of enzyme systems, mast cells, thromboplastin, platelets, electrical currents, blood coagulability and viscosity, catecholamines, uric acid,
Cholera Epidemic in Haiti, 2010: Using a Transmission Model to Explain Spatial Spread of Disease and Identify Optimal Control Interventions
Authors: Ashleigh R. Tuite, Joseph Tien, Marisa Eisenberg, David J.D. Earn, Junling Ma, David N. Fisman
Journal: Annals of Internal Medicine (2011)

Background: Haiti is in the midst of a cholera epidemic. Surveillance data for formulating models of the epidemic are limited, but such models can aid understanding of epidemic processes and help define control strategies. Objective: To predict, by using a mathematical model, the sequence and timing of regional cholera epidemics in Haiti and explore the potential effects of disease-control strategies. Design: Compartmental mathematical model allowing person-to-person and waterborne transmission of cholera. Within- and between-region epidemic spread was modeled, with the latter dependent on population sizes and distance between regional centroids (a "gravity" model). Setting: Haiti, 2010 to 2011. Data Sources: Haitian hospitalization data, 2009 census data, literature-derived parameter values, and model calibration. Measurements: Dates of epidemic onset and hospitalizations. Results: The plausible range for cholera's basic reproductive number (R0, defined as the number of secondary cases per primary case in a susceptible population without intervention) was 2.06 to 2.78. The order and timing of regional cholera outbreaks predicted by the gravity model were closely correlated with empirical observations. Analysis of changes in disease dynamics over time suggests that public health interventions have substantially affected this epidemic. A limited vaccine supply provided late in the epidemic was projected to have a modest effect. Limitations: Assumptions were simplified, which was necessary for modeling. Projections are based on the initial dynamics of the epidemic, which may change. Conclusion: Despite limited surveillance data from the cholera epidemic in Haiti, a model simulating between-region disease transmission according to population and distance closely reproduces reported disease patterns. This model is a tool that planners, policymakers, and medical personnel seeking to manage the epidemic could use immediately. Primary Funding Source: None.
A Bio‐inspired Platform to Modulate Myogenic Differentiation of Human Mesenchymal Stem Cells Through Focal Adhesion Regulation
Authors: Haiyang Yu, Chor Yong Tay, Mintu Pal, Wen Shing Leong, Huaqiong Li, Hai Li, Feng Wen, David Tai Leong, Lay Poh Tan
Journal: Advanced Healthcare Materials (2012)

The use of human mesenchymal stem cells (hMSCs) in cardiac-tissue engineering has gained widespread attention and many reports have shown that matrix compliance, micro/nano-patterns could be some of the important biophysical cues that drive hMSCs differentiation. Regardless of the type of biophysical induction cues, cells mainly explore their environment via focal adhesion (FA) and FA plays an important role in many cellular behaviours. Therefore, it is hypothesized that FA modulation through materials manipulation could be an important cue for modulation that would result in the stem cell lineage commitment. In this work, the FA of hMSCs is modulated by a novel microcontact printing method using polyvinyl alcohol as a trans-print media which can successfully print proteins on soft polydimethylsiloxane (PDMS). The FA is successfully modified into dense FA and elongated FA by micropatterning square and rectangular patterns on 12.6 kPa PDMS respectively. Additionally, the combined effects of stiffness of PDMS substrates (hard (308 kPa), intermediate (12.6 kPa)) and FA patterning on hMSCs differentiation are studied. The results indicate that dense FA does not induce myogenesis while elongated FA can promote cytoskeleton alignment and further myogenesis on PDMS with intermediate stiffness of 12.6 kPa. However, on stiff substrate (308 kPa), with or without patterns, the cytoskeleton alignment and myogenesis are not obvious. This demonstrates for the first time that it is possible to induce the differentiation of hMSCs by regulating the FA using a materials platform even in the absence of any biochemical factors. It also shows that there is a synergistic effect between FA regulation and matrix stiffness that results in a more specific and higher up-regulated myogenesis. This platform presents a new chemical/biological-free method to engineer the myogenic differentiation of hMSCs.
Increase in anaphylaxis-related hospitalizations but no increase in fatalities: An analysis of United Kingdom national anaphylaxis data, 1992-2012
Authors: Paul J. Turner, M. Hazel Gowland, Vibha Sharma, Despo Ierodiakonou, Nigel Harper, Tomaz Garcez, Richard Pumphrey, Robert J. Boyle
Journal: Journal of Allergy and Clinical Immunology (2014)

The incidence of anaphylaxis might be increasing. Data for fatal anaphylaxis are limited because of the rarity of this outcome.We sought to document trends in anaphylaxis admissions and fatalities by age, sex, and cause in England and Wales over a 20-year period.We extracted data from national databases that record hospital admissions and fatalities caused by anaphylaxis in England and Wales (1992-2012) and crosschecked fatalities against a prospective fatal anaphylaxis registry. We examined time trends and age distribution for fatal anaphylaxis caused by food, drugs, and insect stings.Hospital admissions from all-cause anaphylaxis increased by 615% over the time period studied, but annual fatality rates remained stable at 0.047 cases (95% CI, 0.042-0.052 cases) per 100,000 population. Admission and fatality rates for drug- and insect sting-induced anaphylaxis were highest in the group aged 60 years and older. In contrast, admissions because of food-triggered anaphylaxis were most common in young people, with a marked peak in the incidence of fatal food reactions during the second and third decades of life. These findings are not explained by age-related differences in rates of hospitalization.Hospitalizations for anaphylaxis increased between 1992 and 2012, but the incidence of fatal anaphylaxis did not. This might be due to increasing awareness of the diagnosis, shifting patterns of behavior in patients and health care providers, or both. The age distribution of fatal anaphylaxis varies significantly according to the nature of the eliciting agent, which suggests a specific vulnerability to severe outcomes from food-induced allergic reactions in the second and third decades.
Atlas of Clinical Gastroenterology, 3rd Edn
Authors: S Ghosh
Journal: Gut (2005)

Pitfalls in diagnosing acute pancreatitisWe thank Jolobe for his letter (Gut 2005;54:1207-8) which mentions the difficulty of establishing the diagnosis of acute pancreatitis in patients with diabetic ketoacidosis.We did not address diagnostic tests and medical intensive care treatment of acute pancreatitis in our article, 1 but reviewed the interventional and surgical treatment strategies in acute pancreatitis.There is no doubt that treatment of acute pancreatitis, including organ failure in its early phase, is solely supportive. 2 Due to improvements in inten- sive care medicine, mortality of severe disease has decreased dramatically over the past decades.However, to treat patient adequately, the correct diagnosis has to be made.Therefore, the first step in the diagnostic process of acute pancreatitis is to think of this disease.According to the latest classification from Atlanta, 3 acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or remote organ systems.From a clinical point of view, acute upper abdominal pain and elevated pancreatic enzyme levels are needed to diagnose acute pancreatitis.As pointed out by Jolobe in his letter, acute pancreatitis is still underdiagnosed under certain clinical conditions, including diabetic ketoacidosis, but also in other clinical situations, such as shock of unknown origin, patients under intensive care treatment, as well as rare causes of the disease.As acute pancreatitis can be associated with diabetic ketoacidosis and the association between these two is a two way cause-and-effect relationship, early imaging of the pancreas is recommended in these patients to establish the correct diagnosis.Our article focused on the surgical and interventional treatment of severe acute pancreatitis.
JNK2 enhances mammary carcinoma cell migration by regulating EPS8 expression and localization.
Authors: S Mitra, C Van Den Berg
Journal: Cancer Research (2009)

Abstract Abstract #2050 Cell migration is a tightly regulated event critical for normal development and adult wound healing, but it is also a key step in the tumor metastasis cascade. Growth factors initiate intra-cellular signaling pathways that stimulate cell movement by virtue of remodeling the actin cytoskeleton. Fine regulation of this process renders a degree of polarity to the cells, altering their cytoskeleton and providing the requisite mechanical torsion to move forward. Breast cancer cells extravasate from their primary site and travel to other organs forming metastatic colonies.Various signaling molecules including members of the Mitogen Activated Protein Kinase (MAPK) such as c-Jun N-Terminal Kinase (JNK) have been implicated in regulating cancer cell migration. How growth factors transmit signals to form dorsal ruffles and filopodia for cell migration is not precisely understood. Additionally, JNK is encoded by three genes, resulting in 10 isoforms, hence its role in metastasis is complicated. Here, we used the Polyoma Virus Middle T Antigen (PyVMT) transgenic mouse model where wildtype jnk2 was expressed or knocked out. In tumors we found that PyVMT jnk2-/- tumors express higher Epidermal Growth Factor Receptor Substrate 8 (EPS8) mRNA and protein. EPS8 was originally identified as a substrate for Epidermal Growth Factor Receptor (EGFR), and was recently reported to have an actin capping function. Hence, EPS8 is a prime candidate for connecting the EGFR signaling to actin cytoskeletion remodeling, and therefore mediate cell migration. In vitro using Boyden Chamber based migration assays, we found that the PyV MT jnk2+/+ cells migrated fivefold more than the PyV MT/jnk2-/- cells. Pan inhibition of JNK using a small peptide inhibitor TAT-JIP VII significantly reduced migration of the PyV MT/jnk2+/+ cells but was ineffective at further reducing PyVMT jnk2-/- cell migration, suggesting that the JNK2 is the major isoform to convey this function. Furthermore, shRNA mediated knock down of EPS8 in the PYVMT jnk2-/- cells, increased migration of these cells to levels comparable with the wild type counterparts. We subsequently undertook immunocytochemistry studies to evaluate EPS8 localization and cytoskeletal changes upon serum stimulation. Cells expressing JNK2 showed more dorsal ruffles upon serum stimulation, and EPS8 localized to the plasma membrane and in dorsal ruffles. In contrast, EPS8 was predominantly localized in focal adhesions in the PyVMT jnk2-/- cells, which may explain their reduced migration potential. Together our model supports an integral role for JNK2 regulation of EPS8 expression and localization to facilitate cell migration. Our current studies are aimed at further deciphering the JNK/EPS8 pathway to understand the exact molecular mechanism by which these proteins regulate a critical step in mammary cancer cell metastasis. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2050.
Upregulation of the tumor suppressor gene menin in hepatocellular carcinomas and its significance in fibrogenesis
Authors: Pierre J. Zindy, Annie L'Helgoualc'h, Dominique Bonnier, Antony Le Béchec, Katia Bourd-Boitin, Chang Xian Zhang, Orlando Musso, Denise Glaise, Marie Bérangère Troadec, Olivier Loréal, Bruno Turlin, Jean Léger, Bruno Clément, Nathalie Théret
Journal: Hepatology (2006)

The molecular mechanisms underlying the progression of cirrhosis toward hepatocellular carcinoma were investigated by a combination of DNA microarray analysis and literature data mining. By using a microarray screening of suppression subtractive hybridization cDNA libraries, we first analyzed genes differentially expressed in tumor and nontumor livers with cirrhosis from 15 patients with hepatocellular carcinomas. Seventy-four genes were similarly recovered in tumor (57.8% of differentially expressed genes) and adjacent nontumor tissues (64% of differentially expressed genes) compared with histologically normal livers. Gene ontology analyses revealed that downregulated genes (n = 35) were mostly associated with hepatic functions. Upregulated genes (n = 39) included both known genes associated with extracellular matrix remodeling, cell communication, metabolism, and post-transcriptional regulation gene (e.g., ZFP36L1), as well as the tumor suppressor gene menin (multiple endocrine neoplasia type 1; MEN1). MEN1 was further identified as an important node of a regulatory network graph that integrated array data with array-independent literature mining. Upregulation of MEN1 in tumor was confirmed in an independent set of samples and associated with tumor size (P = .016). In the underlying liver with cirrhosis, increased steady-state MEN1 mRNA levels were correlated with those of collagen alpha2(I) mRNA (P < .01). In addition, MEN1 expression was associated with hepatic stellate cell activation during fibrogenesis and involved in transforming growth factor beta (TGF-beta)-dependent collagen alpha2(I) regulation. In conclusion, menin is a key regulator of gene networks that are activated in fibrogenesis associated with hepatocellular carcinoma through the modulation of TGF-beta response.
Fundholding in northern region: the first year.
Authors: J Newton, M Fraser, J Robinson, D Wainwright
Journal: BMJ (1993)

<h3>Background</h3> Streamlined discharge communication in transitions of care improvement models improve patient satisfaction, improve patient self-efficacy, and reduce readmissions. Yet, significant variability and quality exists in the After Visit Summary (AVS) which is used to guide the post-discharge needs of the patient. <h3>Objectives</h3> We sought assess the feasibility, fidelity, acceptability, and effectiveness of a standardized, patient-centered AVS. <h3>Methods</h3> Our multiprofessional and multidisciplinary stakeholder team was led by two physicians and had significant institutional support. We employed a tailored, hybrid implementation strategy, blending components from Lean methodology, the Institute for Healthcare Model for Improvement, and the Consolidated Framework for Implementation Research. We assessed the feasibility (e.g. quality of AVS, usability of template), fidelity (e.g. template utilization rates), acceptability (e.g. direct stakeholder feedback, paging-system audit, patient call logs), and effectiveness (e.g. 30-day readmission rates and patient-centeredness) of our intervention (e.g. standardized, patient-centered AVS). <h3>Results</h3> Our AVS template was written at a third grade reading level but retained all clinically-relevant information. Providers and patients approved of the template with 66% mean utilization (range 41% to 80%). After our intervention, we observed decreased 30-day readmissions (19.7% to 16.0%). Notably, after the introduction of AVS template, pages sent decreased by 3.67 pages weekly (95% CI=[−15.7, 14.0]), but this estimate was imprecise. <h3>Conclusions</h3> Reducing variability and improving the quality of discharge communication, not only improves patient outcomes, but may also improve workflow for providers. These improved team dynamics are important to assess when considering an intervention that is operationalized by time and resource deprived employees.
Improving diet and physical activity: 12 lessons from controlling tobacco smoking
Authors: D. Yach
Journal: BMJ (2005)

2][3] In addition, Sir Richard Doll reported this year on 50 years of following British doctors to document the impact of smoking on their health. 4We have reviewed the evidence and approaches taken to control tobacco smoking, well described in these new texts, because of the rapid global increase in the risk factors of unhealthy diets and lack of physical activity.As part of the Oxford Vision 2020 process, 5 we have proposed 12 lessons from tobacco control that might speed up progress in tackling these new public health threats.][8]