tbuckley/cabot-search huggingface dataset:
The cholesterol controversy.
Authors: A. S. Truswell
Journal: BMJ (1992)

Injuries sustained on "bouncy castles" SIR,-We wish to report the dangers of playing on "bouncy castles."A bouncy castle is an inflatable children's playground, consisting essentially of a rubber matress inflated with air.Three walls generally surround the castle, with the fourth side open to allow entry and exit, but some castles are open on all four sides.They are popular in fairgrounds and recreational halls.During last summer five children and one adult were treated at Northwick Park Hospital for injuries sustained while they were playing on bouncy castles.All injuries were to the arm or neck.Three supracondylar fractures of the humerus occurred.Two of these required open reduction and internal fixation with Kirschner wires.The third was managed with a collar and cuff support.A girl aged 6 sustained a fracture of the mid-shaft of the humerus, which was managed with a hanging cast support.The neck injuries occurred in a 52 year old man and a 12 year old boy.These were both soft tissue injuries caused by flexion and were managed conservatively.
Insulin Action in Cells Expressing Truncated or Kinase-Defective Insulin Receptors: Dissection of Multiple Hormone-Signaling Pathways
Authors: Donald A McClain
Journal: Diabetes Care (1990)

An attempt has been made to dissect insulin-signaling pathways by means of in vitro mutagenesis of the insulin receptor. Studies of two mutants are reviewed: a COOH-truncated receptor and a mutant of the ATPbinding site that is tyrosine kinase defective. The COOH-truncated receptor has normal insulin binding and normal endocytosis and undergoes autophosphorylation and activation as a kinase in vitro and in vivo. Loss of the COOH-terminal43 amino acids has, however, impaired the ability of the receptor to signal metabolic events while augmenting its ability to signal mitogenesis. Thus, domains have been partially identified that are separately involved in metabolic and mitogenic signaling, facilitating future studies of these pathways. The kinase-defective receptor is not only biologically inactive, but has a dominant inhibitory effect on the endogenous insulin receptors in the cell. That is, transfected Rat-1 cells carrying defective human receptors still have normally active rat insulin receptors but are incapable of signaling insulin action. The fact that metabolic signaling by insulinlike growth factor I (IGF-I) is intact in these cells allows definition of separate insulin and IGF-I pathways, leading to stimulation of glucose transport. Analysis of dose responsiveness for mitogenesis implies that mitogenic signaling pathways are shared by insulin and IGF-I, however. The utility of these cell lines in defining these pathways is discussed.
Macrophage and Retinal Pigment Epithelium Phagocytosis
Authors: Silvia C. Finnemann, Enrique Rodriguez-Boulan
Journal: The Journal of Experimental Medicine (1999)

Noninflammatory monocyte macrophages use αvβ3 integrin to selectively bind apoptotic cells, initiating their phagocytic removal. In a related process, the retinal pigment epithelium (RPE) employs αvβ5 integrin to recognize spent photoreceptor outer segment particles (OS). Here, we show that apoptotic cells and OS compete for binding to these receptors, indicating that OS and apoptotic cells expose surface signals recognizable by αvβ3 and αvβ5. Particle binding to αvβ5 required protein kinase C (PKC) activation. In RPE, αvβ5 binding was maximally activated even before any phagocytic challenge and was reduced by PKC inhibitors. In macrophages, it was dormant but became activated upon PKC stimulation. PKC-activated αvβ5-mediated binding in macrophages differed from constitutive binding to the same integrin receptor in RPE cells in that the former followed much faster kinetics, similar to particle binding mediated by αvβ3. Activation of αvβ5 for particle binding correlated with its recruitment into a detergent-insoluble fraction, a process sensitive to pharmacological modulation of PKC in both types of phagocytes. Furthermore, αvβ5 but not αvβ3 particle binding required actin microfilaments. These data constitute the first evidence that noninflammatory phagocytes actively regulate the earliest phase of phagocytic clearance, particle binding, by controlling receptor activity.
Aminotransferase levels during treatment of rheumatoid arthritis with leflunomide in clinical practice
Authors: A Hoi
Journal: Annals of the Rheumatic Diseases (2003)

Leflunomide is a disease modifying drug with proven efficacy in the treatment of rheumatoid arthritis (RA).1–6 Clinical trials have indicated that low level, reversible, asymptomatic increases in serum transaminases may occur, although serious hepatotoxicity is uncommon.6–8 It remains unclear as to whether the characteristics of leflunomide transaminitis, reported in clinical trials, occur in a less vigorously monitored and clinically heterogeneous normal care RA population.

Between November 1999 and September 2001 we audited all non-hospital clinic patients with RA, privately managed with leflunomide by one physician (GOL), for the frequency and severity of transaminitis. These patients received usual care and were felt to be more likely to have other comorbidities, polypharmacy, and poorer review compliance than clinical trial patients.

Serum alanine aminotransferase (ALT) …
Functional Attachment of Soft Tissues to Bone: Development, Healing, and Tissue Engineering
Authors: Helen H. Lu, Stavros Thomopoulos
Journal: Annual Review of Biomedical Engineering (2013)

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue–to-bone interface, and concludes with a summary of challenges and future directions.
Incidence of gastric cancer among patients with gastric precancerous lesions: observational cohort study in a low risk Western population
Authors: Huan Song, Isabella Guncha Ekheden, Zongli Zheng, Jan Ericsson, Olof Nyrén, Weimin Ye
Journal: BMJ (2015)

<b>Objective</b> To accurately measure the incidence of gastric cancer among patients with gastric precancerous lesions, and to quantify the excess incidence in comparison with people with normal mucosa on endoscopy and a general population. <b>Design</b> Population based cohort study. <b>Setting</b> Population of Sweden using data from its national disease registers. <b>Participants</b> 405 172 patients who had gastric biopsy samples taken for non-malignant indications between 1979 and 2011. <b>Main outcome measures</b> Incidence of gastric cancer, reported separately for patients with different mucosal changes in biopsy samples. Standardised incidence ratios provided estimation of the relative risk, using the general Swedish population as reference; and hazard ratios were derived from Cox regression modelling for internal comparisons with patients with normal gastric mucosa. <b>Results</b> After excluding the first two years of follow-up, 1599 cases of gastric cancer were identified. The annual crude incidence of gastric cancer was 20×10<sup>−5</sup> for those in the normal mucosa group (standardised incidence ratio 1.0), 42×10<sup>−5</sup> for those with minor changes (1.5), 59×10<sup>−5</sup> for the gastritis group (1.8), 100×10<sup>−5</sup> for the atrophic gastritis group (2.8), 129×10<sup>−5</sup> for the intestinal metaplasia group (3.4), and 263×10<sup>−5</sup> for the dysplasia group (6.5). Cox regression modelling confirmed that excess risks increased monotonically with progressive severity of gastric lesions, with the highest hazard ratio of 10.9 (dysplasia versus normal mucosa, 95% confidence interval 7.7 to 15.4). The increased incidence was stable throughout the follow-up period, and the gaps between cumulative incidence curves grew continuously. <b>Conclusions</b> Among patients who undergo gastroscopy with biopsy for clinical indications, approximately 1 in 256 with normal mucosa, 1 in 85 with gastritis, 1 in 50 with atrophic gastritis, 1 in 39 with intestinal metaplasia, and 1 in 19 with dysplasia will develop gastric cancer within 20 years. These numbers, along with cost-benefit analyses, should guide future surveillance policies for these particular patient groups.
The Phosphoinositide 3-Kinase Inhibitor PI-103 Downregulates Choline Kinase α Leading to Phosphocholine and Total Choline Decrease Detected by Magnetic Resonance Spectroscopy
Authors: Nada M.S. Al-Saffar, L. Elizabeth Jackson, Florence I. Raynaud, Paul A. Clarke, Ana Ramírez de Molina, Juan C. Lacal, Paul Workman, Martin O. Leach
Journal: Cancer Research (2010)

Abstract The phosphoinositide 3-kinase (PI3K) pathway is a major target for cancer drug development. PI-103 is an isoform-selective class I PI3K and mammalian target of rapamycin inhibitor. The aims of this work were as follows: first, to use magnetic resonance spectroscopy (MRS) to identify and develop a robust pharmacodynamic (PD) biomarker for target inhibition and potentially tumor response following PI3K inhibition; second, to evaluate mechanisms underlying the MRS-detected changes. Treatment of human PTEN null PC3 prostate and PIK3CA mutant HCT116 colon carcinoma cells with PI-103 resulted in a concentration- and time-dependent decrease in phosphocholine (PC) and total choline (tCho) levels (P &amp;lt; 0.05) detected by phosphorus (31P)- and proton (1H)-MRS. In contrast, the cytotoxic microtubule inhibitor docetaxel increased glycerophosphocholine and tCho levels in PC3 cells. PI-103–induced MRS changes were associated with alterations in the protein expression levels of regulatory enzymes involved in lipid metabolism, including choline kinase α (ChoKα), fatty acid synthase (FAS), and phosphorylated ATP-citrate lyase (pACL). However, a strong correlation (r2 = 0.9, P = 0.009) was found only between PC concentrations and ChoKα expression but not with FAS or pACL. This study identified inhibition of ChoKα as a major cause of the observed change in PC levels following PI-103 treatment. We also showed the capacity of 1H-MRS, a clinically well-established technique with higher sensitivity and wider applicability compared with 31P-MRS, to assess response to PI-103. Our results show that monitoring the effects of PI3K inhibitors by MRS may provide a noninvasive PD biomarker for PI3K inhibition and potentially of tumor response during early-stage clinical trials with PI3K inhibitors. Cancer Res; 70(13); 5507–17. ©2010 AACR.
Liver biopsy interpretation for causes of late liver allograft dysfunction
Authors: A. J. Demetris
Journal: Hepatology (2006)

Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.
Reporting of Randomized Controlled Trials in Hodgkin Lymphoma in Biomedical Journals
Authors: Thilo Kober, Sven Trelle, Andreas Engert
Journal: JNCI Journal of the National Cancer Institute (2006)

Background : Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The Consolidated Standards for Reporting Trials (CONSORT) statement was introduced in 1996 to improve reporting of RCTs. We aimed to determine the extent of ambiguity and reporting quality as assessed by adherence to the CONSORT statement in published reports of RCTs involving patients with Hodgkin lymphoma from 1966 through 2002. Methods : We analyzed 242 published full-text reports of RCTs in patients with Hodgkin lymphoma. Quality of reporting was assessed using a 14-item questionnaire based on the CONSORT checklist. Reporting was studied in two pre-CONSORT periods (1966–1988 and 1989–1995) and one post-CONSORT period (1996–2002). Results : Only six of the 14 items were addressed in 75% or more of the studies in all three time periods. Most items that are necessary to assess the methodologic quality of a study were reported by fewer than 20% of the studies. Improvements over time were seen for some items, including the description of statistics methods used, reporting of primary research outcomes, performance of power calculations, method of randomization and concealment allocation, and having performed intention-to-treat analysis. Conclusions : Despite recent improvements, reporting levels of CONSORT items in RCTs involving patients with Hodgkin lymphoma remain unsatisfactory. Further concerted action by journal editors, learned societies, and medical schools is necessary to make authors even more aware of the need to improve the reporting RCTs in medical journals to allow assessment of validity of published clinical research.
Exchange Protein Directly Activated by cAMP (epac): A Multidomain cAMP Mediator in the Regulation of Diverse Biological Functions
Authors: Martina Schmidt, Frank J. Dekker, Harm Maarsingh
Journal: Pharmacological Reviews (2013)

Since the discovery nearly 60 years ago, cAMP is envisioned as one of the most universal and versatile second messengers. The tremendous feature of cAMP to tightly control highly diverse physiologic processes, including calcium homeostasis, metabolism, secretion, muscle contraction, cell fate, and gene transcription, is reflected by the award of five Nobel prizes. The discovery of Epac (exchange protein directly activated by cAMP) has ignited a new surge of cAMP-related research and has depicted novel cAMP properties independent of protein kinase A and cyclic nucleotide-gated channels. The multidomain architecture of Epac determines its activity state and allows cell-type specific protein-protein and protein-lipid interactions that control fine-tuning of pivotal biologic responses through the "old" second messenger cAMP. Compartmentalization of cAMP in space and time, maintained by A-kinase anchoring proteins, phosphodiesterases, and <i>β</i>-arrestins, contributes to the Epac signalosome of small GTPases, phospholipases, mitogen- and lipid-activated kinases, and transcription factors. These novel cAMP sensors seem to implement certain unexpected signaling properties of cAMP and thereby to permit delicate adaptations of biologic responses. Agonists and antagonists selective for Epac are developed and will support further studies on the biologic net outcome of the activation of Epac. This will increase our current knowledge on the pathophysiology of devastating diseases, such as diabetes, cognitive impairment, renal and heart failure, (pulmonary) hypertension, asthma, and chronic obstructive pulmonary disease. Further insights into the cAMP dynamics executed by the Epac signalosome will help to optimize the pharmacological treatment of these diseases.
Private specificities of H-2K and H-2D loci as possible selective targets for effector lymphocytes in cell-mediated immunity.
Authors: B D Brondz, I K Egorov, G I Drizlikh
Journal: The Journal of Experimental Medicine (1975)

Receptors of effector T lymphocytes of congeneic strains of mice do not recognize public H-2 specificities and react to private H-2 specificities only. This has been established with the use of three tests: direct cytotoxicity assay of immune lymphocytes upon target cells, specific absorption of the lymphocytes on the target cells, and rejection of skin grafts at an accelerated fashion. Immunization with two private H-2 specificities in the system C57BL/10ScSn leads to B10.D2 induces formation of two corresponding populations of effector lymphocytes in unequal proportion: a greater part of them is directed against the private specificity H-2.33 (Kb), while the smaller part is towards H-2.2 (Db) private specificity. These two populations of effector lymphocytes do not overlap, as demonstrated by experiments on their cross-absorption on B10.D2 (R107), B10.D2 (R101), B10.A(2R), and B10.A(5R) target cells, as well as on mixtures of R107 and R101 targets. Following removal of lymphocytes reacting with one of the private H-2 specificities, lymphocytes specific to the other specificity are fully maintained. A mixture of target cells, each bearing one of the two immunizing private specificities, absorbs 100% of the immune lymphocytes and is totally destroyed by them. It is suggested that H-2 antigens are natural complexes of hapten-carrier type, in which the role of hapten is played by public H-2 specifities and that of the carrier determinant by either private H-2 specificities or structures closely linked to them. Various models of steric arrangement of MHC determinants recognized by receptors of effector T lymphocytes are discussed.
Chemotactic Response of Leukocytes to Cord Factor (Trehalose-6,6′-dimycolate) 2
Authors: I. Ofek, A. Bekierkunst
Journal: JNCI Journal of the National Cancer Institute (1976)

Cord factor (trehalose-6,6'-dimycolate), a glycolipid extractable from myocobacteria, was chemotactic for peritoneal cells of mice at concentrations from 5 to 25 mug/ml medium, as well as for peripheral white blood cells of mice and humans. At higher concentrations, presumably only macrophages were attracted.
Male-pattern baldness susceptibility locus at 20p11
Authors: J Brent Richards, Xin Yuan, Frank Geller, Dawn Waterworth, Veronique Bataille, Daniel Glass, Kijoung Song, Gerard Waeber, Peter Vollenweider, Katja K H Aben, Lambertus A Kiemeney, Bragi Walters, Nicole Soranzo, Unnur Thorsteinsdottir, Augustine Kong, Thorunn Rafnar, Panos Deloukas, Patrick Sulem, Hreinn Stefansson, Kari Stefansson, Tim D Spector, Vincent Mooser
Journal: Nature Genetics (2008)
ANOREXIGENIC AND CATABOLIC EFFECTS OF ANGIOTENSIN II ARE REDOX DEPENDENT: POTENTIAL MECHANISM OF CONGESTIVE HEART FAILURE-ASSOCIATED SKELETAL MUSCLE WASTING
Authors: Sergiy Sukhanov, Laura Semrpun-Prieto, Tadashi Yoshida, Bashir Atteia, Romer Gonzalez-Villalobos, Charlotte Vaughn, Michael Tabony, Patrick Delafontaine
Journal: Journal of the American College of Cardiology (2011)
Frontal fibrosing alopecia: a clinical review of 36 patients
Authors: A. Samrao, A-L. Chew, V. Price
Journal: British Journal of Dermatology (2010)

Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia with a distinctive clinical pattern of progressive frontotemporal hairline recession. Currently, there are no evidence-based studies to guide treatment for patients with FFA; thus, treatment options vary among clinicians.We report clinical findings and treatment outcomes of 36 patients with FFA, the largest cohort to date. Further, we report the first evidence-based study of the efficacy of hydroxychloroquine in FFA using a quantitative clinical score, the Lichen Planopilaris Activity Index (LPPAI).A retrospective case note review was performed of 36 adult patients with FFA. Data were collected on demographics and clinical findings. Treatment responses to hydroxychloroquine, doxycycline and mycophenolate mofetil were assessed using the LPPAI. Adverse events were monitored.Most patients in our cohort were female (97%), white (92%) and postmenopausal (83%). Apart from hairline recession, 75% also reported eyebrow loss. Scalp pruritus (67%) and perifollicular erythema (86%) were the most common presenting symptom and sign, respectively. A statistically significant reduction in signs and symptoms in subjects treated with hydroxychloroquine (P < 0·05) was found at both 6- and 12-month follow up.In FFA, hairline recession, scalp pruritus, perifollicular erythema and eyebrow loss are common at presentation. Despite the limitations of a retrospective review, our data reveal that hydroxychloroquine is significantly effective in reducing signs and symptoms of FFA after both 6 and 12 months of treatment. However, the lack of a significant reduction in signs and symptoms between 6 and 12 months indicates that the maximal benefits of hydroxychloroquine are evident within the first 6 months of use.
Fetal and Infant Mortality in Norway and the United States
Authors: J. David Erickson
Journal: JAMA (1982)

Relative to the countries of northern Europe, the United States has a high crude infant mortality rate. We compared the United States' fetal and infant mortality rates with those of Norway, a nation that is internationally recognized for having a low infant mortality. Norwegian birth-weight-specific rates were applied to the US birth populations, yielding adjusted rates. The adjusted rates, which are the crude rates that would have resulted in the United States if the Norwegian birth-weight-specific rates had been in force, were generally higher than the US rates that were actually observed. Thus, the major reason for the United States' poor international rank is probably its unfavorable birth-weight distributions, and any major improvement in the United States' international standing will likely await a reduction in the proportion of high-risk, low-weight births. (<i>JAMA</i>1982;247:987-991)