tbuckley/cabot-search huggingface dataset:
Oxygen Free Radical Release in Human Failing Myocardium Is Associated With Increased Activity of Rac1-GTPase and Represents a Target for Statin Treatment
Authors: Christoph Maack, Tanja Kartes, Heiko Kilter, Hans-Joachim Schäfers, Georg Nickenig, Michael Böhm, Ulrich Laufs
Journal: Circulation (2003)

Reactive oxygen species (ROS) contribute to the development of heart failure. A potential source of myocardial ROS is the NADPH oxidase, which is regulated by the small GTP-binding protein rac1. Isoprenylation of rac1 can be inhibited by statin therapy. Thus, we examined ROS and rac1 in human failing myocardium and tested their regulation by statins in vivo.In human left ventricular myocardium from patients with ischemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM), NADPH oxidase activity was increased 1.5-fold compared with nonfailing controls (P<0.05, n=8). In failing myocardium, increased oxidative stress determined by measurements of lipid peroxidation and aconitase activity was associated with increased translocation of rac1 from the cytosol to the membrane. Pull-down assays revealed a 3-fold increase of rac1-GTPase activity in ICM and DCM. In parallel, membrane expression of the NADPH oxidase subunit p47phox, but not p67phox, was upregulated in failing compared with nonfailing myocardium. In right atrial myocardium from patients undergoing cardiac surgery who were prospectively treated with atorvastatin or pravastatin (40 mg/d, 4 weeks), rac1-GTPase activity was decreased to 67.9+/-12% and 65.6+/-13.8% compared with patients without statin (P<0.05, n=8). Both atorvastatin and pravastatin significantly reduced angiotensin II-stimulated but not basal NADPH oxidase activity.Failing myocardium of patients with DCM and ICM is characterized by upregulation of NADPH oxidase-mediated ROS release associated with increased rac1 activity. Oral statin treatment inhibits myocardial rac1-GTPase activity. These data suggest that extrahepatic effects of statins can be observed in humans and may be beneficial for patients with chronic heart failure.
Calcifying supracoracoid bursitis as a cause of chronic shoulder pain.
Authors: J Mens, J.K van der Korst
Journal: Annals of the Rheumatic Diseases (1984)

A case of chronic shoulder pain is reported with marked limitation of both active and passive elevations and a normal range of motion of the glenohumeral joint. X-ray examination demonstrated cloudy calcification in the coracoclavicular region, presumably indicating calcifying supracoracoid bursitis.
Inhibition of lymphocyte trapping by a passenger virus in murine ascitic tumors: characterization of lactic dehydrogenase virus (LDV) as the inhibitory component and analysis of the mechanism of inhibition.
Authors: P K Mongini, L T Rosenberg
Journal: The Journal of Experimental Medicine (1976)

Cell-free fluid from several ascites promoting tumors inhibits lymphocyte trapping. Lactic dehydrogenase virus (LDV), a common passenger virus in many mouse tumors, was found to be a trapping inhibitor component in these fluids. Procedures used to eliminate infective LDV, such as dilution, passage of the tumor through irradiated rats, ether fractionation, and ultraviolet (UV) irradiation abolished the trapping inhibitory capacity of the fluids. LDV, dissociated from tumors, was inhibitory. Lymph nodes in mice with acute, but not chronic, LDV infections were inhibited from trapping. LDV does not appear to inhibit the capacity of circulating cells to be trapped, and as measured by mitogen responsiveness, the virus does not directly interfere with T-cell function. LDV may inhibit trapping by indirectly affecting the T cell or directly affecting the macrophage in which it replicates. The known characteristics of LDV infection may explain a number of reported immunosuppressive attributes of tumor-associated ascitic fluids.
Cephalosporin Resistance in Neisseria gonorrhoeae Infections—Reply
Authors: Vanessa G. Allen, Roberto G. Melano, Donald E. Low
Journal: JAMA (2013)

In Reply: Drs Klausner and Kerndt highlight the urgent need for innovative approaches to address the continued emergence of multidrug-resistant N gonorrhoeae. Specifically, by analogy to efforts successful at reducing macrolide-resistant group A streptococci, they suggest real-time detection and antimicrobial testing use may turn the tide of cephalosporin resistance in N gonorrhoeae.
CUTANEOUS ULCERS TREATED BY THE SULPHYDRYL CONTAINING AMINO-ACID CYSTEINE
Authors: LOUIS A. BRUNSTING
Journal: JAMA (1933)

The treatment of cutaneous ulcers by sulphydryl compounds is a clinical application of the investigations of Hammett<sup>1</sup>and of Hammett and Reimann,<sup>2</sup>who found, in a long series of experiments on plants, lower animals and man, that there is a positive correlation between the sulphydryl (SH—) group and cellular activity. Reimann<sup>3</sup>reported favorably on the treatment of obstinate cutaneous ulcers by means of thiocresol, which contains sulphydryl attached to the benzene nucleus. Dressings were saturated with a solution of thiocresol, diluted 1: 10,000, and applied to the wounds for periods of a few days, alternating with bland treatment for a similar period. There were distinct spurts of healing during the time the thiocresol was applied, as shown by epithelial growth and a change in the character and amount of granulation tissue. Following the separation of glutathione in crystalline form, Kendall<sup>4</sup>suggested to us the use, in
Ovulation: Stimulation, Suppression, Detection
Authors: Charles E. Flowers
Journal: JAMA (1967)

This is a timely book. For the majority of the physicians, it fills a void which has resulted from the rapid recent advances in this field.  The book consists of the contributions of 36 international and national authorities in the field of gynecologic endocrinology. It has a meaningful foreword by Bernard Zondek and a beautiful and fitting epilogue by Herbert de Watteville. Between this appropriate beginning and fitting ending are 29 chapters which completely cover the three important aspects of ovulation— stimulation, suppression, and detection.  One is impressed with the clarity of the language, uniform style throughout the book, and the paucity of errors—a tribute to the editing of Dr. Greenblatt. Every chapter is excellent. The mechanisms of ovulation are beautifully described by Dr. Blandau. The gonadotropin secretion in the normal menstrual cycle and the hypothalamic control are particularly well presented. These three chapters in the section on stimulation are
Absence of Epithelial Immunoglobulin a Transport, with Increased Mucosal Leakiness, in Polymeric Immunoglobulin Receptor/Secretory Component–Deficient Mice
Authors: Finn-Eirik Johansen, Marcela Pekna, Inger Natvig Norderhaug, Bjørn Haneberg, Max Albert Hietala, Peter Krajci, Christer Betsholtz, Per Brandtzaeg
Journal: The Journal of Experimental Medicine (1999)

Mucosal surfaces are protected specifically by secretory immunoglobulin A (SIgA) and SIgM generated through external translocation of locally produced dimeric IgA and pentameric IgM. Their active transport is mediated by the epithelial polymeric Ig receptor (pIgR), also called the transmembrane secretory component. Paracellular passive external transfer of systemic and locally produced antibodies also provides mucosal protection, making the biological importance of secretory immunity difficult to assess. Here we report complete lack of active external IgA and IgM translocation in pIgR knockout mice, indicating no redundancy in epithelial transport mechanisms. The knockout mice were of normal size and fertility but had increased serum IgG levels, including antibodies to Escherichia coli, suggesting undue triggering of systemic immunity. Deterioration of their epithelial barrier function in the absence of SIgA (and SIgM) was further attested to by elevated levels of albumin in their saliva and feces, reflecting leakage of serum proteins. Thus, SIgA did not appear to be essential for health under the antigen exposure conditions of these experimental animals. Nevertheless, our results showed that SIgA contributes to maintenance of mucosal homeostasis. Production of SIgA might therefore be a variable in the initiation of human immunopathology such as inflammatory bowel disease or gluten-sensitive enteropathy.
Tl-201 SPECT and F-18 FDG PET for Assessment of Glioma Recurrence versus Radiation Necrosis
Authors: David B. Siepmann, Alan Siegel, Petra J. Lewis
Journal: Clinical Nuclear Medicine (2005)

A 59-year-old man was 7 months status post right occipital craniotomy for resection of a glioblastoma multiforme with subsequent radiation and chemotherapy. On follow-up gadolinium-enhanced conventional magnetic resonance images (MRI), a region of contrast enhancement adjacent to the resection cavity was felt to represent tumor recurrence or focal radiation necrosis. The focus of enhancement on MRI was found to correspond with focal uptake of Tl-201 and abnormally increased metabolic activity on F-18 FDG PET, all consistent with tumor recurrence. Although both the thallium and PET scans were positive, the uptake of FDG by the normal brain creates a relatively low target to background. Because thallium is not concentrated by normal brain, the tumor is much more clearly evident in this examination. Only F-18 FDG PET, however, demonstrated the decreased metabolic activity in adjacent cortex resulting from radiation therapy, a finding which may correlate with clinical symptoms.
Suppression by autogenous complementary idiotypes: the priority of the first response.
Authors: D A Rowley, H Köhler, H Schreiber, S T Kaye, I Lorbach
Journal: The Journal of Experimental Medicine (1976)

Complementary idiotypes or antibodies are considered to have combining site structures which are at least partly directed against each other. Complementary antibodies were induced in A/He mice by immunization with phosphorylcholine (PC)-containing antigens and by immunization with the PC-binding IgA myeloma protein TEPC-15 (T15). Both responses were monitored by enumerating plaque-forming cells (PFC) and assaying serum antibody levels against the corresponding antigens. Mice immunized at least three times with T15 in adjuvants had markedly suppressed responses to subsequent immunization with PC; similarly, mice preimmunized multiple times with PC had suppressed responses to immunizations with T15. In contrast, mice immunized with T15 in the interval between "primary" and "secondary" immunizations with PC had undiminished PFC responses to both antigens but significantly decreased antibody titers to PC. Simultaneous responses were also induced by immunizations with T15 superimposed on weekly immunizations with PC; with this regime, immunization with T15 actually enhanced the PFC response to PC, but serum antibody to PC was significantly lower than for mice immunized with PC only. Levels of serum antibody to PC were probably lower, either because anti-PC antibody was complexed with the complementary antibody directed against T15, or because the antibody directed against T15 prevented synthesis and/or release of anti-PC antibody by cells in vivo. Thus, an established prior autogenous immune response can dramatically suppress a subsequent primary complementary response, but the effects of complementary responses on each other are more complex with different sequences of immunization. Also, the effects of variables such as the amounts and ratios of the classes of antibodies on regulation of complementary responses remain to be defined.
The Family Dermatology Life Quality Index: measuring the secondary impact of skin disease
Authors: M.K.A. Basra, R. Sue-Ho, A.Y. Finlay
Journal: British Journal of Dermatology (2006)

Summary Background Skin diseases are known to have a major impact on the lives of patients and their families. Many instruments are available to measure the health‐related quality of life (HRQoL) of patients but no measure has been developed so far to quantify the secondary impact on family members of the patients. Objectives To develop and validate a dermatology‐specific instrument to measure the adverse impact on the HRQoL of family members of patients with skin disease. Methods Detailed semi‐structured interviews were conducted with family members of patients to identify different aspects of HRQoL affected. An initial draft version of the questionnaire based on the main topic areas was pilot tested to assess the face and content validity. A 10‐item questionnaire, the Family Dermatology Life Quality Index (FDLQI), was finalized after modifications to the draft questionnaire based on feedback from families and dermatology professionals and on item reduction. Psychometric evaluation was conducted on a new cohort of family members (n = 132) who completed the FDLQI and the patients (n = 109) who completed the Dermatology Life Quality Index (DLQI). Results Fifty‐nine different aspects of family members' HRQoL were identified from the analysis of the interviews, which were categorized into main topic areas. Factor analysis of 10 items of the final questionnaire revealed two factors and together these explained 60% of the common variance. The FDLQI demonstrated high internal consistency (Cronbach's α = 0·88) and test–retest (intraclass correlation coefficient = 0·94) reliabilities. The responsiveness of the instrument to change was shown by significant change in the family members' FDLQI scores in cases where patients' clinical condition either improved or worsened. Construct validity was assessed by testing a number of a priori hypotheses. A strong correlation was seen between the family members' FDLQI scores and patients' DLQI scores (r = 0·69), a significantly higher FDLQI score was seen for inflammatory skin diseases compared with noninflammatory diseases/isolated lesions (P < 0·0001), and there was a positive relationship between the family members' FDLQI scores and patients' disease severity (r = 0·49). Conclusions The FDLQI is simple and practical and seems to have the potential to be used as an additional outcome measure in clinical practice and evaluation research.
Secretion of plasminogen activator inhibitor by cultured human epidermal cells
Authors: K. HASHIMOTO, K. NISHIOKA, I. KATAYAMA, K. YOSHIKAWA
Journal: British Journal of Dermatology (1986)

A conditioned medium from cultured human epidermal cells was observed to inhibit the activity of exogenous urokinase. By reverse fibrin autography after SDS polyacrylamide gel electrophoresis, a plasminogen activator inhibitor was detected with a molecular weight of 46,000. Using Mr 33,000 [125I]-labelled urokinase we observed the formation of an enzyme-ligand complex. The molecular weight of this complex was 79, 000. These results indicate that cultured human epidermal cells secrete a plasminogen activator inhibitor (urokinase inhibitor) with a molecular weight of 46,000.
Evolution of Inflammation in Nonalcoholic Fatty Liver Disease: The Multiple Parallel Hits Hypothesis
Authors: Herbert Tilg, Alexander R. Moschen
Journal: Hepatology (2010)

Whereas in most cases a fatty liver remains free of inflammation, 10%-20% of patients who have fatty liver develop inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]). Inflammation may precede steatosis in certain instances. Therefore, NASH could reflect a disease where inflammation is followed by steatosis. In contrast, NASH subsequent to simple steatosis may be the consequence of a failure of antilipotoxic protection. In both situations, many parallel hits derived from the gut and/or the adipose tissue may promote liver inflammation. Endoplasmic reticulum stress and related signaling networks, (adipo)cytokines, and innate immunity are emerging as central pathways that regulate key features of NASH. (Hepatology 2010;52:1836-1846)
Abstract 1057: LPA stimulates EMT of ovarian cancer cells via gip2 and gep oncogenes
Authors: Ji Hee Ha, Jeremy Ward, Danny N. Dhanasekaran
Journal: Cancer Research (2014)

Abstract Ovarian cancer is currently the most fatal gynecological cancer with a 5-year survival rate of only 45%. Recent studies have identified a critical role for lysophosphatidic acid (LPA) in the genesis and the progression of ovarian cancer. In order to identify transcription factors that are induced by LPA, a commercial pathway reporter array was used. Hypoxia induced factor 1 (HIF-1α) induction was the most prominent response showing more than 150 fold transcriptional activation compared with control. LPA treatment under normoxic and hypoxic (1% O2) conditions increased HIF-1α protein level, which leads to epithelial-to-mesenchymal transition (EMT) in the ovarian cancer cell line OVCA432. We also found that stimulation of the OVCA432 cells with LPA at normoxic and hypoxic conditions led to a significant increase of the mRNA and protein expression of the EMT transcription factor Twist. Immunofluorescent imaging confirmed that Twist levels were significantly up-regulated and that Twist was translocated to the nucleus as early as 4 hours after stimulation with LPA in both a normoxic and hypoxic environment. Additionally, immunofluorescent imaging showed that expression of E-cadherin on the periphery of the cell as well as in the whole cell was greatly reduced when cells were stimulated with LPA in normoxic and hypoxic conditions. Finally, our study demonstrated that LPA-mediated induction of EMT required both gip2 and gep oncogenes. Overall, our study indicated that the downstream components regulated by oncogenic G-proteins could potentially be targeted in the future to prevent EMT in ovarian cancer. Citation Format: Ji Hee Ha, Jeremy Ward, Danny N. Dhanasekaran. LPA stimulates EMT of ovarian cancer cells via gip2 and gep oncogenes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1057. doi:10.1158/1538-7445.AM2014-1057
Changes in spontaneous sinus node rate as an estimate of cardiac autonomic tone during stable and unstable ventricular tachycardia
Authors: Heikki V. Uikuri, Liagat Zaman, Agustin Castellanos, Kenneth M. Kessler, Marilyn Cox, Frances Glicksman, Robert J. Myerburg
Journal: Journal of the American College of Cardiology (1989)
Anterior Tibial Pain
Authors: E. B. French, W. H. Price
Journal: BMJ (1962)

initially which fell to normal or near normal levels at subsequent venepunctures.This is shown graphically in the Chart.Clinically these subjects appeared anxious DAY I DAY 2 DAY I DAY 2 too o hrs 2 hrs hrS 2 hrs ohrS 2hrs ohrS 2hrs Z 10 0 :) 3 'U IL 5 0a LOW FAT 50g9.50g9.LOW FAT BUTTER BUTTEREffect of alimentary lipaemia produced by 50 g. of butter on plasma fibrinolytic activity.at the time of the initial venepuncture and the findings illustrate the importance of taking into consideration the effect of anxiety in causing an increase in fibrinolysis.Clearly there is no evidence from the results presented that 50 g. of butter inhibits plasma fibrinolytic activity two hours after its ingestion.Indeed, if the effect of anxiety on the initial reading is ignored the conclusion would be that a low-fat breakfast inhibited fibrinolysis in four of the six subjects (Table V), while 50 g. of butter produced this effect in only one out of six subjects (Table VI).Discussion This study has provided no evidence that alimentary lipaemia produced by 85 g. of animal fat, 85 g. of vegetable fat, or 50 g. of butter inhibits fibrinolysis as measured by the lysis of diluted plasma clots.It cannot, therefore, support the hypothesis that the relationship between high-fat intakes and coronary artery disease canl be explained in part by the effect of dietary fat on fibrinolysis.It does, however, provide an example of how anxiety in the experimental subject may lead to a false interpretation of results.We have already shown that transient anxiety results in a substantial increase in fibrinolytic activity and that such anxiety is usually most prominent at the time of the first venepuncture of a series (Ogston et al., 1962).It is clear that the inclusion of a numlber of anxious subjects in a group who are given the test fat meal on thie first day of an experiment may produce results leading to the conclusion that fat meals inhibit fibrinolysis.Few studies have stated the order in which the high-fat and low-fat meals were given, and this makes it impossible to assess the signi- ficance of some of the results reported. SummaryThe diurnal increase in plasma fibrinolytic activity found in the 31-hour period after a low-fat breakfast was not significantly altered by the alimentary lipaemia produced by meals of 85 g. of animal fat or 85 g. of vegetable fat.Anxiety at the time of the initial venepuncture was associated with high fibrinolytic activity.If the effect of anxiety was ignored the fall in fibrinolytic activity at subsequent venepunctures could lead to the false conclusion that the test meal had inhibited fibrinolysis.A study of patients receiving 50 g. of butter and a low-fat meal on alternate days showed that butter- induced lipaemia also did not affect plasma fibrinolytic activity.We are grateful to Sister I. M. Cowie, Ward 1, Aberdeen Royal Infirmary, for help in the preparation of fat meals, and to the patients for their co-operation.We thank Alfonal Ltd. for the gift of their products.
CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis
Authors: Fatima Teixeira-Clerc, Boris Julien, Pascale Grenard, Jeanne Tran Van Nhieu, Vanessa Deveaux, Liying Li, Valérie Serriere-Lanneau, Catherine Ledent, Ariane Mallat, Sophie Lotersztajn
Journal: Nature Medicine (2006)
Heat and risk of myocardial infarction: hourly level case-crossover analysis of MINAP database
Authors: K. Bhaskaran, B. Armstrong, S. Hajat, A. Haines, P. Wilkinson, L. Smeeth
Journal: BMJ (2012)

<b>Objective</b> To quantify the association between exposure to higher temperatures and the risk of myocardial infarction at an hourly temporal resolution. <b>Design</b> Case-crossover study. <b>Setting</b> England and Wales Myocardial Ischaemia National Audit Project (MINAP) database. <b>Participants</b> 24 861 hospital admissions for myocardial infarction occurring in 11 conurbations during the warmest months (June to August) of the years 2003-09. <b>Main outcome measure</b> Odds ratio of myocardial infarction for a 1°C increase in temperature. <b>Results</b> Strong evidence was found for an effect of heat acting 1-6 hours after exposure to temperatures above an estimated threshold of 20°C (95% confidence interval 16°C to 25°C). For each 1°C increase in temperature above this threshold, the risk of myocardial infarction increased by 1.9% (0.5% to 3.3%, P=0.009). Later reductions in risk seemed to offset early increases in risk: the cumulative effect of a 1°C rise in temperature above the threshold was 0.2% (−2.1% to 2.5%) by the end of the third day after exposure. <b>Conclusions</b> Higher ambient temperatures above a threshold of 20°C seem to be associated with a transiently increased risk of myocardial infarction 1-6 hours after exposure. Reductions in risk at longer lags are consistent with heat triggering myocardial infarctions early in highly vulnerable people who would otherwise have had a myocardial infarction some time later ("short term displacement"). Policies aimed at reducing the health effects of hot weather should include consideration of effects operating at sub-daily timescales.