tbuckley/cabot-search huggingface dataset:
Effects of intravenous prostacyclin in variant angina.
Authors: S Chierchia, C Patrono, F Crea, G Ciabattoni, R De Caterina, G A Cinotti, A Distante, A Maseri
Journal: Circulation (1982)

A lack in prostacyclin (PGI2) production due to atherosclerosis may play a role in the pathophysiology of some of the clinical manifestations of ischemic heart disease and in particular, of coronary vasospasm. We therefore evaluated the effects of i.v. PGI2 in nine patients with variant angina and six normal volunteers. In normal subjects, PGI2 (2.5, 5, 10 and 20 micrograms/kg/min) had significant antiplatelet effects, caused a dose-dependent decrease in both systolic and diastolic arterial pressure and a decrease in pulmonary resistance. Heart rate increased in a dose-dependent manner, but no consistent effects on myocardial contractility (evaluated by ultrasound) were observed. Side effects were negligible and readily reversible. Although producing obvious antiplatelet and vasodilatory effects, PGI2 did not affect the number, severity and duration of spontaneous ischemic episodes due to coronary vasospasm in five patients and ergonovine-induced spasm in three. However, the number of ischemic episodes was consistently reduced in one patient during four consecutive periods of PGI2 infusion alternated with placebo. a severe, prolonged ischemic episode with ST elevation and pain was consistently observed in this patient every time PGI2 was discontinued. In the appropriate environment, PGI2 can be administered safely to patients with ischemic heart disease. Occasionally, PGI2 may result in a complete disappearance of ischemic episodes due to coronary vasospasm, but usually it is ineffective. These conflicting results could be related to different etiologies of coronary spasm.
Thymosin β4 Increases the Potency of Transplanted Mesenchymal Stem Cells for Myocardial Repair
Authors: Lei Ye, Pengyuan Zhang, Sue Duval, Liping Su, Qiang Xiong, Jianyi Zhang
Journal: Circulation (2013)

Thymosin β4 (Tβ4) has been shown to enhance the survival of cultured cardiomyocytes. Here, we investigated whether the cytoprotective effects of Tβ4 can increase the effectiveness of transplanted swine mesenchymal stem cells (sMSCs) for cardiac repair in a rat model of myocardial infarction (MI).Under hypoxic conditions, cellular damage (lactate dehydrogenase leakage), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelingc cells), and caspase-8 activity were significantly lower, whereas B-cell lymphoma-extra large protein expression was significantly higher, in sMSCs cultured with Tβ4 (1 μg/mL) than in sMSCs cultured without Tβ4, and Tβ4 also increased sMSC proliferation. For in vivo experiments, animals were treated with basal medium (MI: n=6), a fibrin patch (Patch: n=6), a patch containing sMSCs (sMSC: n=9), or a patch containing sMSCs and Tβ4 (sMSC/Tβ4: n=11); Tβ4 was encapsulated in gelatin microspheres to extend Tβ4 delivery. Four weeks after treatment, echocardiographic assessments of left-ventricular ejection fraction and fractional shortening were significantly better (P<0.05) in sMSC/Tβ4 animals (left-ventricular ejection fraction=51.7 ± 1.1%; fractional shortening=26.7 ± 0.7%) than in animals from MI (39 ± 3%; 19.5 ± 1.7%) and Patch (43 ± 1.4%; 21.6 ± 0.9%) groups. Histological assessment of infarct wall thickness was significantly higher (P<0.05) in sMSC/Tβ4 animals (50%, [45%, 80%]) than in animals from MI (25%, [20%, 25%]) group. Measurements in sMSC (left-ventricular ejection fraction=45 ± 2.6%; fractional shortening=22.9 ± 1.6%; TH = 43% [25%, 45%]), Patch, and MI animals were similar. Tβ4 administration also significantly increased vascular growth, the retention/survival of the transplanted sMSCs, and the recruitment of endogenous c-Kit(+) progenitor cells to the infarcted region.Extended-release Tβ4 administration improves the retention, survival, and regenerative potency of transplanted sMSCs after myocardial injury.
Deconstructing media coverage of trastuzumab (Herceptin): an analysis of national newspaper coverage
Authors: Paul M Wilson, Alison M Booth, Alison Eastwood, Ian S Watt
Journal: Journal of the Royal Society of Medicine (2008)

Summary Objective To explore and critically describe the content and main narratives of UK national daily newspaper coverage of trastuzumab (Herceptin®). Design We used the NewsBank database to search eight national daily newspapers, and their Sunday equivalents, retrospectively from 19 February 2006 back to the earliest mention of trastuzumab or Herceptin (19 May 1998). Setting UK national newspapers. Main outcome measures To be eligible for inclusion, articles had to contain at least three sentences about trastuzumab. Articles that focused on the financial performance of companies associated with the drug were excluded from the analysis. For each included article, we extracted bibliographic details and data, and independently rated the reporting slant towards trastuzumab and, where relevant, the reporting slant towards access to treatment. Results We identified 361 articles that met the study inclusion criteria. The proprietary name of Herceptin was always used, with only eight articles mentioning the generic alternative. 294/361 included articles (81.5%) were rated as being positive towards trastuzumab, the remainder rated as neutral. Access to trastuzumab treatment was the main narrative running across included articles and reports of individual patients seeking treatment featured prominently throughout. In 208/361 of included articles (57%) the reporting slant towards access to trastuzumab treatment was rated as negative. 178/361 of included articles (49.3%) mentioned licensing, but rarely mentioned that licensing processes can only occur when the manufacturer applies for a licence. Only a minority of articles mentioned that the drug had to be licensed before it could be subject to the NICE approval process. Conclusions Newspaper coverage of trastuzumab has been characterized by uncritical reporting. Journalists (and consumers) should be more questioning when confronted with information about new drugs and of the motives of those who seek to set the news agenda.
Psychology without brains
Authors: Justin Leiber
Journal: Behavioral and Brain Sciences (1997)

Rachlin's “teleological behaviorism” is a dubious melange. Of Aristotle's four basic “causes” – formal, efficient, material, and final – the scientists and philosophers of the modern era expelled the last, or teleology, from science. Adaptionist evolutionary biologists now sometimes sanction talk of the function or purpose of organisms' structures and behavioral repertoires as a first step because they believe evolution through natural selection makes natural organisms look as if they are purposively designed. But, as Aristotle himself insisted, humans are as much artificial as natural and so teleology is much less appropriate. To the degree that Rachlin's view makes sense it seems to amount to Daniel Dennett's intentional stance or the folk psychology talk of our everyday narrations of ourselves and others.
Glucan: Attempts To Demonstrate Therapeutic Activity Against Five Syngeneic Tumors in Guinea Pigs and Mice2
Authors: J. T. Hunter, M. S. Meltzer, E. Ribi, I. J. Fidler, M. G. Hanna, B. Zbar, H. J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Glucan: Attempts To Demonstrate Therapeutic Activity Against Five Syngeneic Tumors in Guinea Pigs and Mice Get access J. T. Hunter, J. T. Hunter Search for other works by this author on: Oxford Academic PubMed Google Scholar M. S. Meltzer, M. S. Meltzer Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Ribi, E. Ribi Search for other works by this author on: Oxford Academic PubMed Google Scholar I. J. Fidler, I. J. Fidler Search for other works by this author on: Oxford Academic PubMed Google Scholar M. G. Hanna, Jr., M. G. Hanna, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar B. Zbar, B. Zbar Search for other works by this author on: Oxford Academic PubMed Google Scholar H. J. Rapp H. J. Rapp Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 2, February 1978, Pages 419–424, https://doi.org/10.1093/jnci/60.2.419 Published: 01 February 1978 Article history Received: 27 June 1977 Accepted: 23 August 1977 Published: 01 February 1978
Alterations in the Gut Microbiota Associated with HIV-1 Infection
Authors: Catherine A. Lozupone, Marcella Li, Thomas B. Campbell, Sonia C. Flores, Derek Linderman, Matthew J. Gebert, Rob Knight, Andrew P. Fontenot, Brent E. Palmer
Journal: Cell Host & Microbe (2013)

Understanding gut microbiota alterations associated with HIV infection and factors that drive these alterations may help explain gut-linked diseases prevalent with HIV. 16S rRNA sequencing of feces from HIV-infected individuals revealed that HIV infection is associated with highly characteristic gut community changes, and antiretroviral therapy does not consistently restore the microbiota to an HIV-negative state. Despite the chronic gut inflammation characteristic of HIV infection, the associated microbiota showed limited similarity with other inflammatory states and instead showed increased, rather than decreased, diversity. Meta-analysis revealed that the microbiota of HIV-infected individuals in the U.S. was most similar to a Prevotella-rich community composition typically observed in healthy individuals in agrarian cultures of Malawi and Venezuela and related to that of U.S. individuals with carbohydrate-rich, protein- and fat-poor diets. By evaluating innate and adaptive immune responses to lysates from bacteria that differ with HIV, we explore the functional drivers of these compositional differences.
Congenital disorders of glycosylation in hepatology: The example of polycystic liver disease
Authors: Manoe J. Janssen, Esmé Waanders, Jannes Woudenberg, Dirk J. Lefeber, Joost P.H. Drenth
Journal: Journal of Hepatology (2009)

Autosomal dominant polycystic liver disease (PCLD) is a rare progressive disorder characterized by an increased liver volume due to many (>20) fluid-filled cysts of biliary origin. Disease causing mutations in PRKCSH or SEC63 are found in approximately 25% of the PCLD patients. Both gene products function in the endoplasmic reticulum, however, the molecular mechanism behind cyst formation remains to be elucidated. As part of the translocon complex, SEC63 plays a role in protein import into the ER and is implicated in the export of unfolded proteins to the cytoplasm during ER-associated degradation (ERAD). PRKCSH codes for the beta-subunit of glucosidase II (hepatocystin), which cleaves two glucose residues of Glc(3)Man(9)GlcNAc(2) N-glycans on proteins. Hepatocystin is thereby directly involved in the protein folding process by regulating protein binding to calnexin/calreticulin in the ER. A separate group of genetic diseases affecting protein N-glycosylation in the ER is formed by the congenital disorders of glycosylation (CDG). In distinct subtypes of this autosomal recessive multisystem disease specific liver symptoms have been reported that overlap with PCLD. Recent research revealed novel insights in PCLD disease pathology such as the absence of hepatocystin from cyst epithelia indicating a two-hit model for PCLD cystogenesis. This opens the way to speculate about a recessive mechanism for PCLD pathophysiology and shared molecular pathways between CDG and PCLD. In this review we will discuss the clinical-genetic features of PCLD and CDG as well as their biochemical pathways with the aim to identify novel directions of research into cystogenesis.
NHS England is criticised for failing to robustly oversee out of hours care
Authors: G. Iacobucci
Journal: BMJ (2014)

A senior MP has warned of a “serious governance failure” in the monitoring of GP out of hours services, after an official audit found that NHS England was failing to adequately monitor the variation in quality and value for money being achieved across the country.

Margaret Hodge, chairwoman of the parliamentary Public Accounts Committee, said that the report by the National Audit Office1 had revealed deficiencies in the current system that needed to be tackled urgently.

The report noted that, while some commissioners were achieving value for money with their spending on out of hours GP services, this was “not the case across the board.” It also criticised NHS England for taking a year to issue guidance to its 27 area teams about how to seek assurance on out of hours services, and it questioned whether the current monitoring arrangements were fit for purpose, as clinical commissioning groups …
Urinary Phthalate Metabolite Concentrations and Diabetes among Women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008
Authors: Tamarra James-Todd, Richard Stahlhut, John D. Meeker, Sheena-Gail Powell, Russ Hauser, Tianyi Huang, Janet Rich-Edwards
Journal: Environmental Health Perspectives (2012)

Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetes-related risk factors among women.We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study.We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001-2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessment-estimated insulin resistance, and glycosylated hemoglobin A1c.After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (ΣDEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ΣDEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance.Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.
Evaluation of quality of life instruments for COPD care and research
Authors: Saskia Weldam, Marieke Schuurmans, Rani Liu, Jan-Willem Lammers
Journal: European Respiratory Journal (2011)

Background:  Quality of Life (QOL) measurements to quantify the impact in Chronic Obstructive Pulmonary Disease (COPD) with a standardized method has become important in the last decades. A variety of QOL instruments are available. To facilitate decision making with regard to an appropriate QOL instrument in COPD care and research, a systematic review was performed.   Objective:  To identify and evaluate content and psychometric properties of currently available QOL instruments in COPD care and research.   Method:  A systematic literature search was done. Based on criteria, 2 investigators independently identified eligible studies. Methodological quality and data on psychometric properties were assessed by using the Consensus based Standards for selection of health status Measurement Instruments (Mokkink  et al.  J Clin Epidem 2010;63:737-45).   Results:  56 Studies, 11 disease-specific and 10 generic QOL instruments are identified. Methodological studies9 quality is mostly rated fair. In 50 studies theoretically derived hypotheses are not described. In 34 studies confirmatory factor analysis was not performed. Measurement properties are in general positive. Chronic Respiratory Questionnaire has slightly better results than generic measures: hypothesis testing correlation>0.5, Chronbach9s α>0.7, Intra Class Correlation (ICC) 0.5-0.9. The new COPD assessment test α=0.88, ICC= 0.8. Disease-specific instruments hold domains like dyspnea and activity. Social activity, emotional status, anxiety and pain are mostly included in generic instruments.   Conclusion:  Since both disease-specific and generic domains are important in measurement of QOL in COPD patients, we recommend to use at least two QOL instruments covering as many domains as possible.
Helicobacter pylori eradication induces marked increase in H+/K+-adenosine triphosphatase expression without altering parietal cell number in human gastric mucosa
Authors: H Osawa
Journal: Gut (2005)

Gastric acid secretion is downregulated by Helicobacter pylori infection and upregulated after its eradication, but the mechanisms are still unclear. We examined the effects of H pylori eradication on the number of parietal cells and on expression of molecules functioning in acid secretion in the human gastric mucosa.We enrolled 111 consecutive men with chronic gastritis induced by H pylori. Biopsy specimens were endoscopically obtained before and 12 weeks after successful eradication of H pylori and parietal cell numbers were counted. mRNA expression levels of H+/K+-adenosine triphosphatase (H+/K+-ATPase), anion exchanger 2, M3 muscarinic receptor, intrinsic factor, and interleukin 1beta were determined with a real time reverse transcriptase-polymerase chain reaction method. The severity of gastric atrophy was evaluated using the serum pepsinogen I/II ratio.No significant difference was observed in parietal cell numbers before and after H pylori eradication. Median mRNA expression levels of H+/K+-ATPase in the gastric mucosa increased 250-fold after H pylori eradication accompanied by attenuation of interleukin 1beta. A large increase in H+/K+-ATPase expression was observed even in patients with severe atrophic gastritis. In contrast, fold increases in mRNA expression levels, including intrinsic factor, anion exchanger 2, and M3 muscarinic receptor, after eradication therapy, were limited to 1.4, 2.3, and 2.5 times, respectively.In the absence of alteration of parietal cell number, gastric H+/K+-ATPase mRNA expression was markedly restored after successful H pylori eradication, suggesting a central role for the restoration of H+/K+-ATPase expression in gastric acid secretion recovery after H pylori eradication.
Innate lymphoid cells facilitate NK cell development through a lymphotoxin-mediated stromal microenvironment
Authors: Tae-Jin Kim, Vaibhav Upadhyay, Vinay Kumar, Kyung-Mi Lee, Yang-Xin Fu
Journal: The Journal of Experimental Medicine (2014)

Natural killer (NK) cell development relies on signals provided from the bone marrow (BM) microenvironment. It is thought that lymphotoxin (LT) α1β2 expressed by the NK cell lineage interacts with BM stromal cells to promote NK cell development. However, we now report that a small number of RORγt+ innate lymphoid cells (ILCs), and not CD3−NK1.1+ cells, express LT to drive NK development. Similar to LT−/− or RORγt−/− mice, the mice conditionally lacking LTα1β2 on RORγt+ ILCs experience a developmental arrest at the immature NK stages, between stages of NK development to the mature NK cell stage. This developmental block results in a functional deficiency in the clearance of NK-sensitive tumor cells. Reconstitution of Thy1+ ILCs from BM or purified RORγt+ ILCs from lamina propria lymphocytes into LT-deficient RORγt+ BM cultures rescues NK cell development. These data highlight a previously undiscovered role of RORγt+ ILCs for NK cell development and define LT from ILCs as an essential molecule for the stromal microenvironment supporting NK cell development.
The Last Hug
Authors: George Young
Journal: JAMA (2002)

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Studies on hematopoietic stem cells: XI. Lack of erythroid burst‐forming units (BFU‐E) in patients with aplastic anemia
Authors: Yoshiaki Moriyama, Masatsugu Sato, Yasutami Kinoshita
Journal: American Journal of Hematology (1979)

The marrow concentration of erythropoietic precursors was examined in normal donors and patients with idiopathic aplastic anemia using a plasma clot culture system. On time course observations the heterogeneity of human erythroid precursors assayable in culture was demonstrated. To evaluate human erythropoiesis in vitro, the benzidine-positive colonies were divided into three groups: small colony, containing 8-50 cells; medium-sized colony, containing 50-500 cells; and large colony, containing more than 500 cells. The majority of the large colonies assumed the morphology of erythropietic bursts (BFU-E) consisted of several subcolonies. The small colonies were counted as CFU-E1, the medium-sized as CFU-E2, and the large as BFU-E to evaluate the erythroid precursor cell compartment in aplastic anemia. The marrow concentration of CFU-E1 and CFU-E2 was shown to be quantitatively diminished in aplastic anemia. In addition, there was no ability of the marrow cells from aplastic patieints to grow BFU-E in vitro even in the presence of a large dose of erythropoietin. This lack of BFU-E colony growth may play an important role in the mechanism of the erythropoietic deficiency in aplastic anemia.