tbuckley/cabot-search huggingface dataset:
Peroxisome Proliferator-Activated Receptor γ and Growth Inhibition by Its Ligands in Uterine Endometrial Carcinoma
Authors: Kyoko Ota, Kiyoshi Ito, Takashi Suzuki, Sumika Saito, Mitsutoshi Tamura, Shin-ichi Hayashi, Kunihiro Okamura, Hironobu Sasano, Nobuo Yaegashi
Journal: Clinical Cancer Research (2006)

Abstract Purpose: In this study, we evaluated the correlation between endometrial carcinoma and peroxisome proliferator-activated receptor γ (PPARγ) expression and assessed whether PPARγ ligands influence carcinoma growth. Experimental Design: We examined the presence and cellular distribution of PPARγ protein in 42 normal endometria, 32 endometria with hyperplasia, and 103 endometria with endometrial carcinoma by immunohistochemistry. We then compared PPARγ mRNA expression in endometrial carcinoma with that in normal endometria using real-time reverse transcription-PCR. We subsequently confirmed expression of PPARγ mRNA by real-time reverse transcription-PCR and PPARγ protein by immunoblotting in endometrial carcinoma cell lines (Ishikawa, Sawano, and RL95-2 cells). We further examined the effects of PPARγ agonist 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a naturally occurring PPARγ ligand, to these endometrial carcinoma cell lines. We also examined the status of apoptosis and p21 mRNA expression of these endometrial carcinoma cell lines following addition of 15d-PGJ2. Results: PPARγ immunoreactivity was detected in 11 of 23 (48%) of proliferative-phase endometrium, 14 of 19 (74%) of secretory-phase endometrium, 27 of 32 (84%) of endometrial hyperplasia, and 67 of 103 (65%) of carcinoma cases. PPARγ immunoreactivity was significantly lower in endometrial carcinoma than in secretory-phase endometrium (P = 0.012) and endometrial hyperplasia (P = 0.006). There was a significant positive association between the status of PPARγ and p21 expression in endometrial carcinoma (P &amp;lt; 0.0001). There was a significant negative association between the body mass index and PPARγ labeling index of carcinoma tissue in the patients with endometrial carcinoma (P &amp;lt; 0.0001). PPARγ mRNA was expressed abundantly in normal endometria but not in endometrial carcinoma. We showed that PPARγ agonist 15d-PGJ2 inhibited cell proliferation and induced p21 mRNA of endometrial carcinoma cell lines. Conclusion: We showed the expression of PPARγ in human endometrial carcinoma and the effects of PPARγ ligand in endometrial carcinoma cells. These findings suggest that a PPARγ ligand, 15d-PGJ2, has antiproliferative activity against endometrial carcinoma.
Angiotensin Converting Enzyme Inhibitors and Progressive Renal Insufficiency
Authors: William F. Keane
Journal: Annals of Internal Medicine (1989)

Study Objective: To review the rationale for using angiotensin converting enzyme (ACE) inhibitors in progressive renal disease, and to evaluate the experience with these agents in patients with hypertension and renal insufficiency. Data Identification: Experimental and clinical studies published from January 1977 to November 1988 were identified by searching the literature and by extensive hand searching of bibliographies of identified articles. Study Selection: Experimental studies of glomerular function during therapy with ACE inhibitors or other antihypertensive regimens were reviewed. Series using ACE inhibitors for treating hypertensive patients with renal disease were evaluated and reports of adverse events were studied. Results of Data Synthesis: Experimentally, ACE inhibitors seem to decrease glomerular injury by reducing both systemic and glomerular hypertension. Clinically, ACE inhibitors reduce systemic blood pressure in hypertensive patients with diabetic and nondiabetic renal disease without causing dramatic changes in glomerular filtration rate or renal blood flow. Most studies of nondiabetic renal insufficiency suggest that proteinuria is reduced in most patients. However, no long-term controlled study on the effect of ACE inhibitors on the progression rate of nondiabetic renal disease has been completed. ACE inhibitors have not yet been approved by the Food and Drug Administration (FDA) for treating or preventing progressive renal disease. Such use would therefore be considered "innovative" therapy. Conclusions: ACE inhibitors are tolerated by azotemic patients, although transient reductions in renal function can occur. Patients with bilateral renal insufficiency or low cardiac output are at increased risk for developing reversible acute renal insufficiency. Hyperkalemia may occur, particularly in patients with diabetes or severe renal insufficiency. In many patients with renal disease, ACE inhibitors dramatically reduce proteinuria, but whether they also reduce the rate of progression of renal disease remains unproved.
Effect of pranlukast, an oral leukotriene receptor antagonist, on leukotriene D4 (LTD4) challenge in normal volunteers
Authors: T. C. O'Shaughnessy, P. Georgiou, K. Howland, M. Dennis, C. H. Compton, N. C. Barnes
Journal: Thorax (1997)

There is increasing evidence to show that leukotrienes are important mediators in asthma. Leukotriene receptor antagonists protect against antigen and exercise challenges in patients with chronic asthma. A study was undertaken to investigate the activity of the leukotriene receptor antagonist pranlukast (SB 205312, ONO-1078) in blocking bronchoconstriction induced by leukotriene D4 (LTD4) inhalation. The selectivity of pranlukast was evaluated using histamine challenge.Pranlukast, 450 mg twice daily, was given to eight healthy non-smoking men for five days in a randomised, double blind, placebo controlled, crossover study. The specific airways conductance (sGaw) was measured before and after bronchial provocation with inhaled LTD4 at 3.5 hours after the first dose and at 3.5 and 9.5 hours after the last dose of pranlukast on the morning of day 5. The concentration of LTD4 required to produce a fall in sGaw of 35% (PC35) was calculated. Subjects also underwent a histamine challenge 3.5 hours after a single dose of pranlukast, 450 mg, or placebo.A single dose of pranlukast produced a 10.6 fold increase in PC35sGaw (95% confidence interval (CI) 4.4 to 25.5; p < 0.001) for LTD4 at 3.5 hours after dosing compared with placebo. Three and a half hours after the morning dose of pranlukast on day 5 the PC35sGaw for LTD4 was increased 25.9 fold (95% CI 10.8 to 62.2; p < 0.001) and was still increased sevenfold (95% CI 2.9 to 16.7; p < 0.001) relative to placebo 9.5 hours after administration of the morning dose. No significant differences were noted for the PC35sGaw to histamine for pranlukast compared with placebo.This study shows that pranlukast is a potent and selective LTD4 receptor antagonist in humans which blocks LTD4 challenge after initial and repeated administration when given twice daily for five days.
<i>Mycobacterium tuberculosis</i>and the host response
Authors: Stefan H.E. Kaufmann, Stewart T. Cole, Valerie Mizrahi, Eric Rubin, Carl Nathan
Journal: The Journal of Experimental Medicine (2005)

Mycobacterium tuberculosis remains a leading cause of morbidity and mortality worldwide. Advances reported at a recent international meeting highlight insights and controversies in the genetics of M. tuberculosis and the infected host, the nature of protective immune responses, adaptation of the bacillus to host-imposed stresses, animal models, and new techniques.
Systematic review of pregnancy in women with inherited cardiomyopathies
Authors: Sébastien P.J. Krul, Jasper J. van der Smagt, Maarten P. van den Berg, Krystyna M. Sollie, Petronella G. Pieper, Karin Y. van Spaendonck‐Zwarts
Journal: European Journal of Heart Failure (2011)
Effects of Treatment Targets on Subsequent Cardiovascular Events in Chinese Patients With Type 2 Diabetes
Authors: Alice P.S. Kong, Xilin Yang, Gary T.C. Ko, Wing-Yee So, Wing-Bun Chan, Ronald C.W. Ma, Vanessa W.S. Ng, Chun-Chung Chow, Clive S. Cockram, Peter C.Y. Tong, Vivian Wong, Juliana C.N. Chan
Journal: Diabetes Care (2007)

International guidelines recommend optimal control of risk factors in diabetes to prevent cardiovascular events. We examined risk associations between achieving treatment targets for glycemia, blood pressure and lipid control, and other risk factors on subsequent cardiovascular events in Chinese patients with type 2 diabetes.Between 1995 and 2005, 6,386 Chinese type 2 diabetic patients without a history of coronary heart disease (CHD) or stroke were recruited. They were classified according to the number of treatment targets attained at baseline, and their cardiovascular outcomes were compared. Treatment targets were defined as A1C <7.0%, blood pressure <130/80 mmHg, and LDL cholesterol <2.6 mmol/l.After a median follow-up of 5.7 years, cumulative incidence of CHD or stroke (n = 749) increased with decreasing numbers of treatment targets attained at baseline. Attainment of two or more targets at baseline was associated with reduced risk of CHD compared with those with no target achieved (hazard ratio 0.69 [95% CI 0.50-0.94], P = 0.020). However, the association lost its significance after adjustment for urinary albumin-to-creatinine ratio, estimated glomerular filtration rate, and hemoglobin.Reaching more treatment targets was associated with reduced risk of new onset of CHD in Chinese patients with type 2 diabetes.
Enthesitis and ankylosis in spondyloarthropathy: What is the target of the immune response?
Authors: J Braun
Journal: Annals of the Rheumatic Diseases (2000)

A report from a symposium held at Klinikum Benjamin Franklin, Free University, Berlin, Germany, 25–26 February 2000 This symposium was organised by J Braun and J Sieper (Free University, Berlin) to review the current knowledge of the anatomical, inflammatory, microbiological, and immunological events in enthesitis. The term "enthesopathy" is relatively new and its medical history short, but some important contributions can be listed (boxFB1). Figure FB1 History of "enthesopathy" • 1966 Enthesopathy first used by Niepel • 1970 Entheses centrally affected in ankylosing spondylitis, in contrast with rheumatoid arthritis (RA; Heberden oration lecture by Ball) • 1975 Some enthesitis in sacroiliitis (François) • 1983 Syndrome of seronegative enthesopathy and arthropathy in children (Rosenberg) • 1982 Sacroiliitis starts in the subchondral bone (Shichikawa) • 1991 Enthesopathy discriminative feature of spondyloarthropathy (SpA; European Spondyloarthropathy Study Group criteria, Dougados) • 1998 Entheses more commonly affected in arthritis in SpA compared with RA (McGonagle) The spondyloarthropathies are among the most common inflammatory rheumatic diseases.1 In addition to the strong genetic predisposition, partly due to HLA-B27,2 there are characteristic clinical features of SpA3: inflammatory back pain often due to sacroiliitis4 and enthesitis occurring mostly at various well defined locations, predominantly of the legs, such as the Achilles tendon, the plantar aponeurosis, the knee, the trochanter regions of the femur, and several pelvic sites.5 Thus entheses are ubiquitous, resulting in a diversity of associated pathological manifestations. Sacroiliitis is the most common early sign of SpA.6Whether or not ligamentous and entheseal structures are affected in sacroiliac inflammation has not yet been entirely clarified. To answer some of the most critical questions an expert symposium on enthesitis was organised:
Induction of vesicular steatosis by amiodarone and tetracycline is associated with up‐regulation of lipogenic genes in heparg cells
Authors: Sébastien Anthérieu, Alexandra Rogue, Bernard Fromenty, André Guillouzo, Marie-Anne Robin
Journal: Hepatology (2011)

Drug-induced liver injury occurs in general after several weeks and is often unpredictable. It is characterized by a large spectrum of lesions that includes steatosis and phospholipidosis. Many drugs such as amiodarone and tetracycline have been reported to cause phospholipidosis and/or steatosis. In this study, acute and chronic hepatic effects of these two drugs were investigated using well-differentiated human hepatoma HepaRG cells. Accumulation of typical lipid droplets, labeled with Oil Red O, was observed in hepatocyte-like HepaRG cells after repeat exposure to either drug. Amiodarone caused the formation of additional intracytoplasmic vesicles that did not stain in all HepaRG cells. At the electron microscopic level, these vesicles appeared as typical lamellar bodies and were associated with an increase of phosphatidylethanolamine and phosphatidylcholine. A dose-dependent induction of triglycerides (TG) was observed after repeat exposure to either amiodarone or tetracycline. Several genes known to be related to lipogenesis were induced after treatment by these two drugs. By contrast, opposite deregulation of some of these genes (FASN, SCD1, and THSRP) was observed in fat HepaRG cells induced by oleic acid overload, supporting the conclusion that different mechanisms were involved in the induction of steatosis by drugs and oleic acid. Moreover, several genes related to lipid droplet formation (ADFP, PLIN4) were up-regulated after exposure to both drugs and oleic acid. Conclusion: Our results show that amiodarone causes phospholipidosis after short-term treatment and, like tetracycline, induces vesicular steatosis after repeat exposure in HepaRG cells. These data represent the first demonstration that drugs can induce vesicular steatosis in vitro and show a direct relationship between TG accumulation and enhanced expression of lipogenic genes. (HEPATOLOGY 2011;)
Transendocardial Autologous Bone Marrow Mononuclear Cell Injection in Ischemic Heart Failure
Authors: Hans F.R. Dohmann, Emerson C. Perin, Christina M. Takiya, Guilherme V. Silva, Suzana A. Silva, Andre L.S. Sousa, Claudio T. Mesquita, Maria-Isabel D. Rossi, Bernardo M.O. Pascarelli, Isabella M. Assis, Helio S. Dutra, João A.R. Assad, Rodrigo V. Castello-Branco, Cantidio Drummond, Hans J.F. Dohmann, James T. Willerson, Radovan Borojevic
Journal: Circulation (2005)

Background— Cell-based therapies for treatment of ischemic heart disease are currently under investigation. We previously reported the results of a phase I trial of transendocardial injection of autologous bone marrow mononuclear (ABMM) cells in patients with end-stage ischemic heart disease. The current report focuses on postmortem cardiac findings from one of the treated patients, who died 11 months after cell therapy. Methods and Results— Anatomicopathologic, morphometric, and immunocytochemical findings from the anterolateral ventricular wall (with cell therapy) were compared with findings from the interventricular septum (normal perfusion and no cell therapy) and from the inferoposterior ventricular wall (extensive scar tissue and no cell therapy). No signs of adverse events were found in the cell-injected areas. Capillary density was significantly higher ( P &lt;0.001) in the anterolateral wall than in the previously infarcted tissue in the posterior wall. The prominent vasculature of the anterolateral wall was associated with hyperplasia of pericytes, mural cells, and adventitia. Some of these cells had acquired cytoskeletal elements and contractile proteins (troponin, sarcomeric α-actinin, actinin), as well as the morphology of cardiomyocytes, and appeared to have migrated toward adjacent bundles of cardiomyocytes. Conclusions— Eleven months after treatment, morphological and immunocytochemical analysis of the sites of ABMM cell injection showed no abnormal cell growth or tissue lesions and suggested that an active process of angiogenesis was present in both the fibrotic cicatricial tissue and the adjacent cardiac muscle. Some of the pericytes had acquired the morphology of cardiomyocytes, suggesting long-term sequential regeneration of the cardiac vascular tree and muscle.
PAIN, ITCH AND ENDORPHINS
Authors: John A. Summerfield
Journal: British Journal of Dermatology (1981)

Journal Article PAIN, ITCH AND ENDORPHINS Get access John A. Summerfield John A. Summerfield Visiting Scientist, Liver Diseases Section, Digestive Diseases Branch, NIAMDD, National Institutes of Health, Bethesda, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 105, Issue 6, 1 December 1981, Pages 725–726, https://doi.org/10.1111/j.1365-2133.1981.tb00985.x Published: 01 December 1981
The Structure of Genetic and Environmental Risk Factors for Syndromal and Subsyndromal Common DSM-IV Axis I and All Axis II Disorders
Authors: Kenneth S. Kendler, Steven H. Aggen, Gun Peggy Knudsen, Espen Røysamb, Michael C. Neale, Ted Reichborn-Kjennerud
Journal: American Journal of Psychiatry (2010)

The authors sought to clarify the structure of the genetic and environmental risk factors for 22 DSM-IV disorders: 12 common axis I disorders and all 10 axis II disorders.The authors examined syndromal and subsyndromal axis I diagnoses and five categories reflecting number of endorsed criteria for axis II disorders in 2,111 personally interviewed young adult members of the Norwegian Institute of Public Health Twin Panel.Four correlated genetic factors were identified: axis I internalizing, axis II internalizing, axis I externalizing, and axis II externalizing. Factors 1 and 2 and factors 3 and 4 were moderately correlated, supporting the importance of the internalizing-externalizing distinction. Five disorders had substantial loadings on two factors: borderline personality disorder (factors 3 and 4), somatoform disorder (factors 1 and 2), paranoid and dependent personality disorders (factors 2 and 4), and eating disorders (factors 1 and 4). Three correlated environmental factors were identified: axis II disorders, axis I internalizing disorders, and externalizing disorders versus anxiety disorders.Common axis I and II psychiatric disorders have a coherent underlying genetic structure that reflects two major dimensions: internalizing versus externalizing, and axis I versus axis II. The underlying structure of environmental influences is quite different. The organization of common psychiatric disorders into coherent groups results largely from genetic, not environmental, factors. These results should be interpreted in the context of unavoidable limitations of current statistical methods applied to this number of diagnostic categories.
Randomized Phase II Trials: A Long-term Investment With Promising Returns
Authors: M. R. Sharma, W. M. Stadler, M. J. Ratain
Journal: JNCI Journal of the National Cancer Institute (2011)

Given the multitude of novel anticancer drugs and the limited resources available to study them, phase II trials should identify drugs with the highest probability of succeeding in subsequent phase III trials. Currently, single-arm phase II trial results are interpreted relative to historical control subjects, introducing selection bias and confounding that may limit the validity of the conclusions. The rate of success (defined as a statistically significant difference between arms) in phase III oncology trials is only 40%, suggesting that current phase II trials are insufficiently informative. However, simulation studies suggest that randomized phase II trials would have lower error rates and greater predictive power for phase III results. Randomized phase II trials may also be more informative than single-arm phase II trials because of the hypotheses being tested, the variety of possible endpoints, and the opportunities for biomarker discovery. There are a wide variety of randomized phase II designs that can be used, including the randomized discontinuation design, the delayed-start design, adaptive (Bayesian) designs, selection designs, and phase II/III designs. The barriers to widespread adoption of randomized phase II trials include time to completion, sample size considerations, and ethical concerns, but none are insurmountable. We conclude that randomized phase II trials are a worthy investment considering finite patient and financial resources and should be the rule rather than the exception for evaluating novel therapies in oncology.
Evolution of a Polymorphic Regulatory Element in Interferon-γ Through Transposition and Mutation
Authors: Hans Ackerman, Irina Udalova, Jeremy Hull, Dominic Kwiatkowski
Journal: Molecular Biology and Evolution (2002)

Mammalian transposable elements have intrinsic regulatory elements that can activate neighboring genes, and it is speculated that they can also carry extrinsic transactivating DNA sequences to new genomic locations. We have identified a polymorphic segment of the human interferon-γ promoter region where two adjacent binding sites for NF-κB and NFAT originated from the insertion of an Alu element approximately 22–34 MYA. Both binding sites lie outside the Alu consensus sequence but within the boundaries of the insertion, suggesting that this segment of DNA was comobilized when the Alu element moved from another part of the genome. Sequence comparisons and examination of DNA-protein interactions across nine different primate species indicate that the inserted sequence contained the intact NFAT binding site, whereas the ability to bind NF-κB evolved through a series of mutations after the insertion. These observations are consistent with the notion that retropseudogenes can comobilize intact regulatory sequences to new locations and thereby influence the evolution of gene regulatory networks; however, the extent to which such events have shaped the evolution of gene regulation remains unknown.
Home-Based Versus Mobile Clinic HIV Testing and Counseling in Rural Lesotho: A Cluster-Randomized Trial
Authors: Niklaus Daniel Labhardt, Masetsibi Motlomelo, Bernard Cerutti, Karolin Pfeiffer, Mashaete Kamele, Michael A. Hobbins, Jochen Ehmer
Journal: PLoS Medicine (2014)

Niklaus Labhardt and colleagues investigate how different HIV testing and counseling strategies, based on home visits or mobile clinics, reach different populations in a rural African setting. Please see later in the article for the Editors' Summary