tbuckley/cabot-search huggingface dataset:
Lipoproteins, Coagulation States, and Risk of Thrombotic Events
Authors: Charles R. Spillert
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The results of clinical studies correlating lipoprotein levels with risk for thrombotic events like myocardial infarction are inconsistent and not sensitive indicators of risk.<sup>1</sup>One may assume that these thrombotic events are causally related to hypercoagulability and that protection from these events is associated with relative hypocoagulability. Regrettably, there is no coagulation test to detect a prothrombotic (high-risk) state or antithrombotic (low-risk) state as a marker of the effects of lipoproteins. We here describe the utilization of a modified recalcification time (MRT) test to document the adverse coagulation-accelerating effect of low-density lipoproteins (LDLs) and the beneficial coagulation-retarding property of high-density lipoproteins (HDLs). This test was described in detail in a recent article.<i>2</i>Unlike other tests, by using whole blood, the MRT incorporates the role of both cellular and chemical participants in coagulation. Also, incubating blood with an activator like a lipoprotein induces the monocyte to
Stress: metaplastic effects in the hippocampus
Authors: Jeansok J Kim, Kenneth S Yoon
Journal: Trends in Neurosciences (1998)

Memory impairments, which occur regularly across species as a result of aging, disease and psychological insults (for example, stress), constitute a useful area for investigation into the neurobiological basis of learning and memory. Memory researchers have identified the hippocampus as a crucial brain structure involved in key aspects of memory formation. The most widely accepted putative mechanisms of memory storage in this structure are LTP and LTD. The hippocampus is enriched with receptors for corticosterone (a glucocorticoid hormone released in response to stress) and it plays a role in glucocorticoid negative feedback and, therefore, some hippocampal functioning might be particularly susceptible to stress. In support of this view, stress-induced modifications in learning, synaptic plasticity and endangerment of neurons have been seen in the hippocampus. Stress and glucocorticoids appear to exert a metaplastic effect through the modulation of Ca2+ levels. We propose a synaptic model that provides a conceptual scaffold to structure our understanding of the manifold actions of stress on the hippocampus. Accordingly, we suggest that stress-induced metaplasticity could disrupt Ca2+ homeostasis and thus endanger hippocampal neurons.
Gastric motor effects of peptide and non-peptide ghrelin agonists in mice in vivo and in vitro
Authors: T Kitazawa
Journal: Gut (2005)

<b>Background and aims:</b> The gastroprokinetic activities of ghrelin, the natural ligand of the growth hormone secretagogue receptor (GHS-R), prompted us to compare the effect of ghrelin with that of synthetic peptide (growth hormone releasing peptide 6 (GHRP-6)) and non-peptide (capromorelin) GHS-R agonists both in vivo and in vitro. <b>Methods:</b> In vivo, the dose dependent effects (1–150 nmol/kg) of ghrelin, GHRP-6, and capromorelin on gastric emptying were measured by the <sup>14</sup>C octanoic breath test which was adapted for use in mice. The effect of atropine, N<sup>G</sup>-nitro-L-arginine methyl ester hydrochloride (l-NAME), or D-Lys<sup>3</sup>-GHRP-6 (GHS-R antagonist) on the gastroprokinetic effect of capromorelin was also investigated. In vitro, the effect of the GHS-R agonists (1 µM) on electrical field stimulation (EFS) induced responses was studied in fundic strips in the absence and presence of L-NAME. <b>Results:</b> Ghrelin, GHRP-6, and capromorelin accelerated gastric emptying in an equipotent manner, with bell-shaped dose-response relationships. In the presence of atropine or l-NAME, which delayed gastric emptying, capromorelin failed to accelerate gastric emptying. D-Lys<sup>3</sup>-GHRP-6 also delayed gastric emptying but did not effectively block the action of the GHS-R agonists, but this may be related to interactions with other receptors. EFS of fundic strips caused frequency dependent relaxations that were not modified by the GHS-R agonists. L-NAME turned EFS induced relaxations into cholinergic contractions that were enhanced by ghrelin, GHRP-6, and capromorelin. <b>Conclusion:</b> The <sup>14</sup>C octanoic breath test is a valuable technique to evaluate drug induced effects on gastric emptying in mice. Peptide and non-peptide GHS-R agonists accelerate gastric emptying of solids in an equipotent manner through activation of GHS receptors, possibly located on local cholinergic enteric nerves.
Cytotoxic T-cell responses to H-Y: mapping of the Ir genes.
Authors: M Hurme, C M Hetherington, P R Chandler, E Simpson
Journal: The Journal of Experimental Medicine (1978)

The secondary cytotoxic responses to the male specific antigen (H-Y) in in mice show H-2 restrictions so that cytotoxic female cells must share K and/or D end antigen with the male target cells. The production of cytotoxic cells is under the control of Ir genes, thus offering the possibility of studying the function of Ir genes in H-2-restricted cytotoxic responses. There are two kinds of Ir genes regulating this response; the dominant gene in the H-2b haplotype and complementary genes in other haplotypes. Now we have been able to map the dominant gene and some of the complementary genes: the dominant genes is in IAb, and in H-2k/H-2d complementation, the Ir genes are in ICk and ICd, and in H-2k/H2s and H-2k/H-2q complementations, at least the H-2k gene is in IC.
A measurement of the active state in heart muscle
Authors: A. J. Brady
Journal: Cardiovascular Research (1971)

A measurement of the active state in heart muscle Get access Allan J. Brady Allan J. Brady From the Department of Physiology and the Los Angeles County Cnrdiocoscular Research Laboratory, Unicersity of Calijornia at Los Angeles, Center for Health Sciences, Los Angeles, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 5, Issue supp1, July 1971, Pages 11–17, https://doi.org/10.1093/cvr/5.supp1.11 Published: 01 July 1971
Animal Models of the Asthmatic State
Authors: Roy Patterson, J F Kelly
Journal: Annual Review of Medicine (1974)

Asthma is a common but poorly understood response of the lower respiratory tract of humans, which has and will require considerable investigative effort in order to define the basic mechanisms involved. Only limited studies can be done in asthmatic humans for safety reasons. Appropriate animal models are necessary to test hypoth­ eses of underlying mechanisms in this disease and to determine the significance of immunologic, pharmacologic, and cellular factors in human asthma. This discussion will include a brief review of the characteristics of asthma, the types of animal models that have evolved with comments on how tQese systems might relate to the human disease state, and, finally, summaries of some of the studies that have been carried out using these animal respiratory responses. Human asthma has been characterized clinically as recurrent wheezing dyspnea occurring in patients with bronchial hyperreactivity to a variety of stimuli. Physio­ logically asthma is characterized by reversible obstruction of the bronchi, such reversibility demonstrated most commonly by the administration of ,8-adrenergic agonists. An additional characteristic has been the clinical experimental observation that the hyperreactivity of the bronchi 'can be demonstrated by the administration of histamine, methyJcholine or, more recently, prostaglandin F2a (1). In minimal asthma there may be no pathologic changes observed in respiratory tissues but in asthma of long duration a thickened basement membrane and eosinophilia have been found at autopsy (2). Immunologically, one type of asthma is related to reaginic antibodies of the E class of immunoglobulins. This type of asthma may be associated with elevated serum concentrations of IgE (3) and the specific IgE antibodies may be demonstrated by in vivo skin tests or in vitro radioimmunoassay systems. Clinically, asthma is classified traditionally as either extrinsic or intrinsic. Extrin­ sic asthma is precipitated by inhalation of antigen, which reacts with IgE antibody fixed to mast cells in the lung with resultant mediator release. These mediators are 'Supported by USPHS Grants AI 11403 and AI 000 57 and the Ernest S. Bazley Grant.
Late Pleistocene Australian Marsupial DNA Clarifies the Affinities of Extinct Megafaunal Kangaroos and Wallabies
Authors: Bastien Llamas, Paul Brotherton, Kieren J. Mitchell, Jennifer E.L. Templeton, Vicki A. Thomson, Jessica L. Metcalf, Kyle N. Armstrong, Marta Kasper, Stephen M. Richards, Aaron B. Camens, Michael S.Y. Lee, Alan Cooper
Journal: Molecular Biology and Evolution (2014)

Understanding the evolution of Australia's extinct marsupial megafauna has been hindered by a relatively incomplete fossil record and convergent or highly specialized morphology, which confound phylogenetic analyses. Further, the harsh Australian climate and early date of most megafaunal extinctions (39–52 ka) means that the vast majority of fossil remains are unsuitable for ancient DNA analyses. Here, we apply cross-species DNA capture to fossils from relatively high latitude, high altitude caves in Tasmania. Using low-stringency hybridization and high-throughput sequencing, we were able to retrieve mitochondrial sequences from two extinct megafaunal macropodid species. The two specimens, Simosthenurus occidentalis (giant short-faced kangaroo) and Protemnodon anak (giant wallaby), have been radiocarbon dated to 46–50 and 40–45 ka, respectively. This is significantly older than any Australian fossil that has previously yielded DNA sequence information. Processing the raw sequence data from these samples posed a bioinformatic challenge due to the poor preservation of DNA. We explored several approaches in order to maximize the signal-to-noise ratio in retained sequencing reads. Our findings demonstrate the critical importance of adopting stringent processing criteria when distant outgroups are used as references for mapping highly fragmented DNA. Based on the most stringent nucleotide data sets (879 bp for S. occidentalis and 2,383 bp for P. anak), total-evidence phylogenetic analyses confirm that macropodids consist of three primary lineages: Sthenurines such as Simosthenurus (extinct short-faced kangaroos), the macropodines (all other wallabies and kangaroos), and the enigmatic living banded hare-wallaby Lagostrophus fasciatus (Lagostrophinae). Protemnodon emerges as a close relative of Macropus (large living kangaroos), a position not supported by recent morphological phylogenetic analyses.
Low Prevalence of Subclinical Atherosclerosis in Asymptomatic Patients With Type 1 Diabetes in a European Mediterranean Population. Diabetes Care 2014;37:814–820
Authors: Eva Aguilera, Enric Serra, M. Luisa Granada, Núria Alonso, Silvia Pellitero, Eduarda Pizarro, Jordi Lluís Reverter, Isabel Salinas, Berta Soldevila, Dídac Mauricio, Manel Puig-Domingo
Journal: Diabetes Care (2014)

In the print version of the article cited above, the affiliation for Eva Aguilera, Enric Serra, Nuria …
Changes in dietary fat and declining coronary heart disease in Poland: population based study
Authors: Witold A Zatonski, Walter Willett
Journal: BMJ (2005)

and lipid profiles among men. 4 For Estonia, highly educated adults, compared with those with less education, gained a considerable advantage during the 1990s, in terms of mortality from circulatory diseases and total mortality. 5 According to Lawlor and colleagues, the children of these highly educated parents may paradoxically have the poorest insulin resistance profile.We cannot say how much of a paradox this really is, however, as we know nothing about whether their parents as children also had a poor insulin profile.Genetic, fetal, and early childhood factors should all be relevant in determining insulin resistance.In Lawlor and colleagues' study, parental education was important for insulin resistance among prepubertal and postpubertal children.Parental education can be taken as a measure of social circumstances when their children were born-that is, before the collapse of the Soviet system.Income was measured in 1997-2000; for Estonia this means when new food markets had opened up.In mutual adjustments, education but not income had an independent effect; thus it seems unlikely that it is consumption of "burgers, crisps, and processed food" that is creating the pattern of high insulin resistance among children of highly educated parents.We also noted that, in this study, children of highly educated fathers in Estonia had a 200 g lower birth weight than others, consistent with their higher insulin resistance.Anomalies such as those reported for Estonia and Portugal may be of special significance, as they point towards gaps in our understanding and warn against too simplistic a view of health inequalities.Correctly understanding the development of health and mortality in the formerly communist led countries of central and eastern Europe is likely to challenge (and has already challenged) many cherished epidemiological "truths."We thank Ilona Koupil for important comments to a previous version of this commentary.
An Institute for Health-Care Evaluation
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1982)

In July 1980, I wrote an editorial in these columns supporting the evaluation of medical technology as an effective way to moderate the cost of medical care while improving its quality.1 "What we need," I said then, "is a major new national program of support for the evaluation of medical procedures of all kinds —those we now have, and those that we will be developing. The work will have to be done mostly in the private sector and it will need large-scale funding...." I suggested that all third-party payers contribute a small fraction of their annual expenditures to support the . . .
Abstract 464: CXCR7 protein is strongly expressed in B-acute lymphoblastic leukemia (ALL) but not in T-ALL or acute myelogenous leukemia
Authors: Santhi Sridharan, Imran Mirza, Leah A. Marquez-Curtis, A. Robert Turner, Lorree Larratt, Neeta Shirvaikar, Amir Surmawala, Anna Janowska-Wieczorek
Journal: Cancer Research (2012)

Abstract The identification of CXCR7 in addition to CXCR4 as a receptor for the chemokine CXCL12/SDF-1 and recent reports that CXCR7 is expressed in many cancers including breast, lung and prostate prompted us to evaluate the role of CXCR7 in hematological malignancies. While CXCR4 is known to be involved in the progression of acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML), the role of CXCR7 in leukemic dissemination remains unknown. Using immunohistochemistry, we evaluated the expression patterns of CXCR7 and CXCR4 in tissue microarrays (TMAs) constructed from bone marrow biopsies obtained from patients diagnosed with pre B- and B-ALL (n=75; median age 5 yrs, range 6 mo-72 yrs), T-ALL (n=11; median age 12 yrs, range 4-29 yrs) and AML (n=140; median age 62 yrs, range 1-83 yrs). CXCR7 expression was also evaluated at the gene and protein levels in peripheral blood mononuclear cells from ALL and AML patients and in B-cell lines (Raji, NC-37, Ramos, Nalm-6, Reh), T-cell lines (Jurkat, Hut-102B, Sez-4, CEM), and myeloid cell lines (KG-1, HL-60, THP-1, U-937, K562, HEL) using RT-PCR and flow cytometry. We found that in B-and preB-ALL TMAs, CXCR7 was immunopositive in 79% of the patients, in contrast to negative immunostaining in 100% of T-ALL and AML samples. Consistently, flow cytometry showed that CXCR7 protein is expressed on the surface of preB-ALL cells, but not on T-ALL, AML or normal controls. CXCR7 surface expression in the cell lines studied showed that three (NC-37, Raji, Reh) out of five B-cell lines expressed CXCR7, but not in any of the T-cell lines, and only weakly in one (KG-1) of six myeloid cell lines studied. Analysis of the functional role of CXCR7 in leukemia revealed that CXCR7 did not mediate chemotaxis of CXCR7-positive NC-37 B-cell line and CXCR7-negative HL-60 myeloid cell line towards an SDF-1 gradient. However, CXCR7 was found to mediate the trans-endothelial migration, adhesion to HUVEC and survival of NC-37 cells, but not the adhesion to HUVEC or survival of HL-60 cells. In conclusion, the selective strong expression of CXCR7 in B-ALL but not in T-ALL or AML suggests a differential role this protein may play in various types of leukemia. As CXCR7 mediates trans-endothelial migration, adhesion and survival of B-cell line, further investigations into the functional role of CXCR7 in primary B-ALL are warranted with the aim of identifying new therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 464. doi:1538-7445.AM2012-464
Effect of Magnesium on the Monophasic Action Potential During Early Ischemia in the In Vivo Human Heart
Authors: Simon R. Redwood, Peter I. Taggart, Peter M. Sutton, Angela Bygrave, Yaver Bashir, D. Das Purkayastha, A. John Camm, Tom Treasure
Journal: Journal of the American College of Cardiology (1996)
Increased hepatotoxicity of tumor necrosis factor-related apoptosis-inducing ligand in diseased human liver
Authors: Xandra Volkmann, Ute Fischer, Matthias J. Bahr, Michael Ott, Frank Lehner, Marion MacFarlane, Gerald M. Cohen, Michael P. Manns, Klaus Schulze-Osthoff, Heike Bantel
Journal: Hepatology (2007)

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) induces apoptosis in tumor cells but not in most normal cells and has therefore been proposed as a promising antitumor agent. Recent experiments suggested that isolated primary human hepatocytes but not monkey liver cells are susceptible to certain TRAIL agonists, raising concerns about the use of TRAIL in cancer treatment. Whether TRAIL indeed exerts hepatotoxicity in vivo and how this is influenced by chemotherapeutic drugs or liver disease are completely unknown. Employing different forms of recombinant TRAIL, we found that the cytokine can induce proapoptotic caspase activity in isolated human hepatocytes. However in marked contrast, these different TRAIL preparations induced little or no cytotoxicity when incubated with tissue explants of fresh healthy liver, an experimental model that may more faithfully mimic the in vivo situation. In healthy liver, TRAIL induced apoptosis only when combined with histone deacetylase inhibitors. Strikingly, however, TRAIL alone triggered massive apoptosis accompanied by caspase activation in tissue explants from patients with liver steatosis or hepatitis C viral infection. This enhanced sensitivity of diseased liver was associated with an increased expression of TRAIL receptors and up-regulation of proapoptotic Bcl-2 proteins. Conclusion: These results suggest that clinical trials should be performed with great caution when TRAIL is combined with chemotherapy or administered to patients with inflammatory liver diseases.
Information sheets for patients with acute chest pain: randomised controlled trial
Authors: J. Arnold, S. Goodacre, P. Bath, J. Price
Journal: BMJ (2009)

<b>Objectives</b> To determine whether providing an information sheet to patients with acute chest pain reduces anxiety, improves health related quality of life, improves satisfaction with care, or alters subsequent symptoms or actions. <b>Design</b> Single centre, non-blinded, randomised controlled trial. <b>Setting</b> Chest pain unit of an emergency department. <b>Participants</b> 700 consecutive patients with acute chest pain and no clear diagnosis at initial presentation. <b>Interventions</b> After a diagnostic assessment patients were randomised to receive either standard verbal advice or verbal advice followed by an information sheet. <b>Main outcome measures</b> The primary outcome was anxiety (hospital anxiety and depression scale). Secondary outcomes were depression (hospital anxiety and depression scale), health related quality of life (SF-36), patient satisfaction, presentation with further chest pain within one month, lifestyle change (smoking cessation, diet, exercise), further information sought from other sources, and planned healthcare seeeking behaviour in response to further pain. <b>Results</b> 494 of 700 (70.6%) patients responded. Compared with those receiving standard verbal advice those receiving advice and an information sheet had lower mean hospital anxiety and depression scale scores for anxiety (7.61 <i>v</i> 8.63, difference 1.02, 95% confidence interval 0.20 to 1.84) and depression (4.14 <i>v</i> 5.28, difference 1.14, 0.41 to 1.86) and higher scores for mental health and perception of general health on the SF-36. The information sheet had no significant effect on satisfaction with care, subsequent symptoms, lifestyle change, information seeking, or planned actions in the event of further pain. <b>Conclusions</b> Provision of an information sheet to patients with acute chest pain can reduce anxiety and depression and improve mental health and perception of general health but does not alter satisfaction with care or other outcomes. <b>Trial registration</b> Current Controlled Trials ISRCTN85248020.
Short Notes of the Opinions and Practice of the Late John Pearson Esq., F.R.S., on Syphilitic Disease
Authors: W. S. Oke
Journal: BMJ (1848)

CASE XII.-" Was admitted in labcur of her seventh child; she had been delivered artificially in her pre- ious Jabours, and lhad but one child born alive.Slhe bad been ill a considerable time before she was brought td the hospital, and in nine bours afterwards, there being no progress made, the pulse 132, her strength much exhausted, and the child dead, she was delivered by the crotcbet."*CASSE XIII.-"This patient was admitted in laboour of her first child; uterine action was feeble, and con- tinued so for serenty-two hours after she came in.As the fietal heart had ceased to act for some time, and the pulse became hurried, it was considered ad- visable to deliver her.The os uteri vas not fully dilated; the bead was high, and resting on the pubes; it was lessened, and cautiously brought down with the crotchet."tCASE XIV.-" Was reported to hare been in labour two days before admnission; the head was high in the pelvis, and pressing strongly on the pubes.It remained *in this situation for twenty-four hours after, during *which time she suffered great distress, uterine action being almost constant.This was her tentb child; she had been twice force-delivered in this hospital; dreading every momnent rupture of the uterus, the head was lessened and brought down by the crotchet, as it had still remained so high as to be scarcely within reach of the finger."+CASE XV.-" Was reported to have been twenty-four hours in labour before admission.About twelve hours after she came in, it was discovered that the face was turned towards the pubes, and pressing so strongly on the urethra the catheter could with difficulty be passed.The pains continued strong for fifteen hours from this time, yet the head did not advance.It was deemed adrisable to lessen it."§ CASE XVI.-" Was tbirty-three hours in labour of her third child without having made the least progress for the last tw'elve.The bladder was forced down before the head.Her pulse became much hurried, and strength greatly exha'usted, rendering immediate delivery necessary.The head was lessened, and the child brought away by the crotchet.It was very large; all her former children were still-born."IjCAsE XVII.-" S. B. was forty hours in Jabour; it wvas her fourth child; all still-born.The head not
Preparation and characterization of starch/cyclodextrin bioadhesive microspheres as platform for nasal administration of Gabexate Mesylate (Foy®) in allergic rhinitis treatment
Authors: Gheorghe Fundueanu, Marieta Constantin, Alessandro Dalpiaz, Fabrizio Bortolotti, Rita Cortesi, Paolo Ascenzi, Enea Menegatti
Journal: Biomaterials (2003)