tbuckley/cabot-search huggingface dataset:
Animal models in endometriosis research
Authors: Ruth Grümmer
Journal: Human Reproduction Update (2006)

Endometriosis is a common gynaecological disease, defined as the presence of endometrial tissue outside the uterus, causing pelvic pain and subfertility in ∼10% of women of reproductive age. Current therapies lead to pain relief, however, do not address the causes and entail severe side effects. Still little is known about the pathogenic processes leading to the development and maintenance of endometriosis. Because endometriosis occurs spontaneously only in humans and some non-human primates, animal models of induced endometriosis have been developed and are of high value for the evaluation of pathophysiological mechanisms underlying the development of this disease. These experimental models include the autotransplantation of uterine fragments into the peritoneal cavity of rodents and non-human primates or the heterotransplantation of human endometrial or endometriotic tissue to immunodeficient mice or onto the chicken chorioallantoic membrane (CAM). This review describes the animal models for endometriosis and assesses their different potentials and limitations in regard to endometriosis research, with the aim of developing novel non-invasive diagnostic tools and improved strategies for the treatment of endometriosis in women.
Epidermal Growth Factor Receptor Kinase Domain Mutations in Esophageal and Pancreatic Adenocarcinomas
Authors: Eunice L. Kwak, Janusz Jankowski, Sarah P. Thayer, Gregory Y. Lauwers, Brian W. Brannigan, Patricia L. Harris, Ross A. Okimoto, Sara M. Haserlat, David R. Driscoll, David Ferry, Beth Muir, Jeff Settleman, Charles S. Fuchs, Matthew H. Kulke, David P. Ryan, Jeff W. Clark, Dennis C. Sgroi, Daniel A. Haber, Daphne W. Bell
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Specific activating mutations within the epidermal growth factor receptor (EGFR) identify a subset of non–small cell lung cancers with dramatic sensitivity to the specific tyrosine kinase inhibitors (TKI), gefitinib and erlotinib. Despite the abundant expression of EGFR protein in a broad range of epithelial cancers, EGFR mutations have not been reported in a substantial fraction of other cancers. Given recent reports of TKI-responsive cases of esophageal and pancreatic cancer, this study was designed to determine the prevalence of EGFR mutations in these gastrointestinal cancers. Experimental Design: We sequenced exons 18 to 21 of EGFR from 21 cases of Barrett's esophagus, 5 cases of high-grade esophageal dysplasia, 17 cases of esophageal adenocarcinoma, and 55 cases of pancreatic adenocarcinoma. Subsets of esophageal (n = 7) and pancreatic cancer cases (n = 5) were obtained from patients who were subsequently treated with gefitinib or erlotinib-capecitabine, respectively. Results: Mutations of EGFR were identified in two esophageal cancers (11.7%), three cases of Barrett's esophagus (14.2%), and two pancreatic cancers (3.6%). The mutations consisted of the recurrent missense L858R and in-frame deletion delE746-A750, previously characterized as activating EGFR mutations in non–small cell lung cancer. We also identified the TKI drug resistance–associated EGFR T790M mutation in an untreated case of Barrett's esophagus and the corresponding adenocarcinoma. Conclusion: The presence of activating mutations within EGFR in both esophageal and pancreatic adenocarcinomas defines a previously unrecognized subset of gastrointestinal tumors in which EGFR signaling may play an important biological role. EGFR mutations in premalignant lesions of Barrett's esophagus also point to these as an early event in transformation of the esophageal epithelium. The role of genotype-directed TKI therapy should be tested in prospective clinical trials.
Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive
Authors: Anneke G. Bosga-Bouwer, Gustaaf W. van Imhoff, Ronald Boonstra, Anneke van der Veen, Eugenia Haralambieva, Anke van den Berg, Bauke de Jong, Vanessa Krause, Martin C. Palmer, Robert Coupland, Philip M. Kluin, Eva van den Berg, Sibrand Poppema
Journal: Blood (2003)
Growth arrest and DNA damage 45G down-regulation contributes to janus kinase/signal transducer and activator of transcription 3 activation and cellular senescence evasion in hepatocellular carcinoma
Authors: Li Zhang, Zhaojuan Yang, Aihui Ma, Yulan Qu, Suhua Xia, Dongxu Xu, Chao Ge, Bijun Qiu, Qiang Xia, Jinjun Li, Yongzhong Liu
Journal: Hepatology (2013)

Growth arrest and DNA damage 45G (GADD45G), a stress sensor with multiple implications in various biological processes, is down-regulated in a broad spectrum of cancers. However, little is known about the biological effects of GADD45G on hepatocellular carcinoma (HCC) cells and the related mechanisms. In the present study, we found that GADD45G was commonly down-regulated in oncogene-transformed mouse liver cells and in human and mouse HCC. Ectopic expression of GADD45G robustly elicited senescence in HCC cells and suppressed tumor growth in vivo. Furthermore, GADD45G-induced senescence occurred in HCC cells independently of p53, p16(INK4a) (p16), and retinoblastoma (Rb). Instead, the prompt inhibition of Janus kinase 2 (Jak2), tyrosine kinase 2 (Tyk2), and signal transducer and activator of transcription 3 (Stat3) activation was observed in cells undergoing senescence. Impairment of Jak-Stat3 activation caused by GADD45G expression was associated with activation of SH2 domain-containing protein tyrosine phosphatase-2 (Shp2). Expression of constitutively activated Stat3 or human telomerase reverse transcriptase (hTERT), as well as knockdown of Shp2f, efficiently counteracted GADD45G-induced senescence. More important, in clinical HCC specimens, we found that GADD45G expression was inversely correlated with phosphorylated Stat3 expression in tumor cells and disease progression.GADD45G functions as a negative regulator of the Jak-Stat3 pathway and inhibits HCC by inducing cellular senescence. The decrease or absence of GADD45G expression may be a key event for tumor cells or premalignant liver cells to bypass cellular senescence.
Left atrial versus bi-atrial maze operation using intraoperatively cooled-tip radiofrequency ablation in patients undergoing open-heart surgery
Authors: Thomas Deneke, Krishna Khargi, Peter Hubert Grewe, Stefan von Dryander, Frank Kuschkowitz, Thomas Lawo, Klaus-Michael Müller, Axel Laczkovics, Bernd Lemke
Journal: Journal of the American College of Cardiology (2002)
The Transcription Factor Early Growth Response 1 (Egr-1) Advances Differentiation of Pre-B and Immature B Cells
Authors: Adelheid Dinkel, Klaus Warnatz, Birgit Ledermann, Antonius Rolink, Peter F. Zipfel, Kurt Bürki, Hermann Eibel
Journal: The Journal of Experimental Medicine (1998)

In mature B lymphocytes, the zinc finger transcription factor early growth response 1 (Egr-1) is one of the many immediate-early genes induced upon B cell antigen receptor engagement. However, its role during earlier stages of lymphopoiesis has remained unclear. By examining bone marrow B cell subsets, we found Egr-1 transcripts in pro/pre-B and immature B lymphocytes, and Egr-1 protein in pro/pre-B–I cells cultivated on stroma cells in the presence of interleukin (IL)-7. In recombinase-activating gene (RAG)-2–deficient mice overexpressing an Egr-1 transgene in the B lymphocyte lineage, pro/pre-B–I cells could differentiate past a developmental block at the B220low BP-1− stage to the stage of B220low BP-1+ pre-B–I cells, but not further to the B220low BP-1+ CD25+ stage of pre-B–II cells. Therefore, during early B lymphopoiesis progression from the B220low BP-1− IL-2R− pro/pre-B–I stage to the B220low BP-1+ IL-2R+ pre-B–II stage seems to occur in at least two distinct steps, and the first step to the stage of B220low BP-1+ pre-B–I cells can be promoted by the overexpression of Egr-1 alone. Wild-type mice expressing an Egr-1 transgene had increased proportions of mature immunoglobulin (Ig)M+ B220high and decreased proportions of immature IgM+ B220low bone marrow B cells. Since transgenic and control precursor B cells show comparable proliferation patterns, overexpression of Egr-1 seems also to promote entry into the mature B cell stage. Analysis of changes in the expression pattern of potential Egr-1 target genes revealed that Egr-1 enhances the expression of the aminopeptidase BP-1/6C3 in pre-B and immature B cells and upregulates expression of the orphan nuclear receptor nur77 in IgM+ B cells.
Smoking habits in patients diagnosed with ANCA associated small vessel vasculitis
Authors: M Haubitz
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To study the prevalence of smoking at onset of symptoms in patients with small vessel vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA). <b>Methods:</b> A retrospective study, in 197 patients with ANCA associated vasculitis, of the history of cigarette smoking at onset of symptoms. Prevalence of smoking in patients with ANCA associated vasculitis was compared with age-specific values for the general population in Germany. <b>Results:</b> 27 (14%) patients were smokers at the time of first disease manifestation (p&lt;0.001, compared with the entire population); 54 (27%) had smoked previously with 1–110 pack-years (median 18) but had stopped ⩾2 years before onset of vasculitis; 116 (59%) patients were lifelong non-smokers. At onset of symptoms, active smokers were younger (median age 42 years) than patients with vasculitis (median 54 years, p&lt;0.01, Mann-Whitney U test) with a lower percentage of women (15%, p&lt;0.005, Fisher's exact test) than in the entire group (47%). Smokers, non-smokers, or ex-smokers did not differ in organ manifestation, mortality, and development of end stage renal disease and relapse rate. <b>Conclusions:</b> The proportion of active smokers in the group of patients with ANCA associated vasculitis is significantly lower than in the entire population. Cigarette smoking may be associated with a reduced risk of ANCA associated vasculitis.
Baroreflex Buffering and Susceptibility to Vasoactive Drugs
Authors: Jens Jordan, Jens Tank, John R. Shannon, Andre Diedrich, Axel Lipp, Christoph Schröder, Guy Arnold, Arya M. Sharma, Italo Biaggioni, David Robertson, Friedrich C. Luft
Journal: Circulation (2002)

The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known.We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects. We used phenylephrine sensitivity during ganglionic blockade as a measure of baroreflex buffering. Phenylephrine (25 microg) increased systolic blood pressure 6+/-1.6 mm Hg in control subjects, 6+/-1.1 mm Hg in orthostatic intolerance patients, 18+/-3.9 mm Hg in patients with essential hypertension, 31+/-3.4 mm Hg in patients with monogenic hypertension, and 25+/-3.4 mm Hg in patients with multiple system atrophy. Similar differences in sensitivities between groups were observed with nitroprusside. The sensitivity to vasoactive drugs was highly correlated with baroreflex buffering function and to a lesser degree with baroreflex control of heart rate. In control subjects, sensitivities to nitroprusside and phenylephrine infusions were correlated with baroreflex heart rate control and sympathetic nerve traffic.Our findings are consistent with an important effect of baroreflex blood pressure buffering on the sensitivity to vasoactive drugs. They suggest that even moderate changes in baroreflex function may have a substantial effect on the sensitivity to vasoactive medications.
Protecting young people from smoking imagery in films: whose responsibility?
Authors: A. Lyons, J. Britton
Journal: Thorax (2011)

Every day thousands of children try a cigarette for the first time, a seemingly innocuous step that for many leads to a lifelong and ultimately fatal addiction to smoking. Preventing this early experimentation is crucially important to preventing the huge toll of death and disability—particularly from respiratory diseases—that smoking causes. There is now increasing international evidence that exposure to smoking behaviour and other imagery in films is a major cause of smoking experimentation and uptake among children and young people.1–3 Three new studies in this issue of Thorax provide further evidence on this effect, this time in UK populations.

In a study of 15-year-old adolescents in the Avon birth cohort, Waylen et al 4 demonstrate a direct relation between exposure to smoking in films and experimentation with smoking which remains significant even after exhaustive adjustment for potential confounders. Among Scottish adolescents exposed to smoking in films, Hunt et al 5 report an exposure-related increase in the odds of smoking that was enhanced by allowance for repeated viewings. In a wider European study, Morgenstern et al 6 demonstrate exposure-related increases in the odds of smoking among adolescents exposed to smoking in films in six countries, including the UK, demonstrating that this association applies across different cultural contexts and levels of implementation of other tobacco control policy. These new studies thus provide further and urgent evidence in support of calls—as yet unheeded—for a radical overhaul of film classification to protect all children and young people from this pervasive and highly damaging imagery.2 3 7–9

The British Board of Film Classification (BBFC) is an independent organisation which, in return for fees paid by film makers, allocates all UK films intended for general release into one of five age classifications (table 1).10 The BBFC lists drug misuse and dangerous imitable …
Increased Expression of Macrophage Colony–Stimulating Factor After Coronary Artery Balloon Injury Is Inhibited by Intracoronary Brachytherapy
Authors: Ariel Finkelstein, Raj Makkar, Terence M. Doherty, Vijaya R. Vegesna, Pinky Tripathi, Ming Liu, Jonathan Bergman, Michael Fishbein, Joerg Hausleiter, Kaname Takizawa, Vladimir Rukshin, Prediman K. Shah, Tripathi B. Rajavashisth
Journal: Circulation (2002)

Background — The mechanisms underlying the reduced neointimal proliferation (NP) by intracoronary brachytherapy (ICBT) are unknown. We hypothesized that ICBT inhibits NP by reducing expression of macrophage colony–stimulating factor (M-CSF). Methods and Results — Thirty coronary arteries from 10 pigs were divided into 3 groups of 10 each: control (C), balloon injury (BI), and BI followed by ICBT (16 Gy at 0.5-mm tissue depth with a 32 P balloon system). Pigs were killed at 24 hours (n=3) and at 7 (n=4) and 14 (n=3) days. Expression of M-CSF was assessed by Western blot, ELISA, and quantitative immunostaining. Persistently increased levels of M-CSF after BI (to 1.4±0.2 nmol/L [ELISA] and 29.4±4.9% of cross-sectional area stained [immunocytochemistry]; P &lt; 0.001 versus control for both) were observed in the injured arteries. Treatment of BI arteries with ICBT reduced M-CSF expression compared with BI alone (to 0.7±0.1 nmol/L [ELISA] and 13.5±2.9% of cross-sectional area stained [immunocytochemistry]; P &lt;0.001 versus BI and P =NS versus control for both) and remained similar to control M-CSF expression for the 14-day study period. Neointimal thickness increased after BI (to 4.8±2.9 mm 2 ; P &lt;0.001 versus control), but this was reduced by ICBT (1.4±0.4 mm 2 ; P &lt;0.001 versus BI). Conclusions — In porcine coronary arteries, BI is associated with increased expression of M-CSF and NP, but neither occurs after ICBT. The beneficial effects of ICBT on NP involve inhibition of M-CSF expression.
Smoking-related lung diseases: a clinical perspective
Authors: B. Balbi, V. Cottin, S. Singh, W. De Wever, F. J. F. Herth, C. Robalo Cordeiro
Journal: European Respiratory Journal (2010)

The cause–effect relationship between a history of cigarette smoking and chronic obstructive pulmonary disease (COPD), emphysema and lung cancer is embedded in a heritage of older studies, although new approaches, classifications and imaging techniques and new treatments have been proposed over the past two decades. In recent years, new players in the field have been added: smoking-related interstitial lung diseases (SR-ILDs) now comprise a number of different presentations, while recently a new entity has been highlighted, i.e. combined pulmonary fibrosis and emphysema (CPFE). This editorial will review the noticeable progress made over the past 20 yrs in our understanding and characterisation of the vast array of abnormalities and clinical pictures pertaining to the respiratory system associated with tobacco smoking.

Great efforts over the years in the diagnostic and therapeutic classification of chronic bronchitis and emphysema resulted in the umbrella term of COPD being adopted. The seminal paper, published in 1995, defined COPD as a condition characterised by “reduced maximum expiratory flow and slow forced emptying of the lungs; features which do not change markedly over several months. Most of the airflow limitation is slowly progressive and irreversible” 1. This was one of the first guideline papers for COPD and it still retains its place in the literature, being the single most quoted article ever published in the European Respiratory Journal !

Imaging techniques have incredibly widened our ability not only to “see” but also as a consequence to better categorise lung disease, including those that are smoking related. High-resolution computed tomography (HRCT) is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. In advanced COPD, airflow limitation is reflected by airway narrowing, airway deformity and extent of emphysema. The degree of airway involvement in COPD can vary greatly for the same degree of airflow obstruction, depending …
Attitudes to the public release of comparative information on the quality of general practice care: qualitative study
Authors: M. N Marshall
Journal: BMJ (2002)

To examine the attitudes of service users, general practitioners, and clinical governance leads based in primary care trusts to the public dissemination of comparative reports on quality of care in general practice, to guide the policy and practice of public disclosure of information in primary care.Qualitative focus group study using mock quality report cards as prompts for discussion.12 focus groups held in an urban area in north west England and a semirural area in the south of England.35 service users, 24 general practitioners, and 18 clinical governance leads.There was general support for the principle of publishing comparative information, but all three stakeholder groups expressed concerns about the practical implications. Attitudes were strongly influenced by experience of comparative reports from other sectors-for example, school league tables. Service users distrusted what they saw as the political motivation driving the initiative, expressed a desire to "protect" their practices from political and managerial interference, and were uneasy about practices being encouraged to compete against each other. General practitioners focused on the unfairness of drawing comparisons from current data and the risks of "gaming" the results. Clinical governance leads thought that public disclosure would damage their developmental approach to implementing clinical governance. The initial negative response to the quality reports seemed to diminish on reflection.Despite support for the principle of greater openness, the planned publication of information about quality of care in general practice is likely to face considerable opposition, not only from professional groups but also from the public. A greater understanding of the practical implications of public reporting is required before the potential benefits can be realised.
Maternal Glucose Concentration During Pregnancy Predicts Fat and Lean Mass of Prepubertal Offspring
Authors: Paula C. Chandler-Laney, Nikki C. Bush, Dwight J. Rouse, Melissa S. Mancuso, Barbara A. Gower
Journal: Diabetes Care (2011)

OBJECTIVE Intrauterine exposure to high maternal glucose is associated with excess weight gain during childhood, but it is not clear whether the excess weight represents increased fat or lean mass. The purpose of this study was to examine the relationship between maternal glucose concentrations during pregnancy and offspring body composition. A secondary goal was to examine whether the association between maternal glucose and children’s body fat was independent of energy intake, energy expenditure, or physical activity. RESEARCH DESIGN AND METHODS Children aged 5–10 years and their biological mothers (n = 27) were recruited. Maternal glucose concentration 1 h after a 50-g oral glucose load, used to screen for gestational diabetes mellitus at 24–28 weeks gestation, was retrieved from medical records. Children underwent dual-energy X-ray absorptiometry to measure body composition, indirect calorimetry to measure resting energy expenditure (REE), accelerometry to measure physical activity, and three 24-h diet recalls to measure energy intake. RESULTS Maternal glucose concentration during pregnancy was positively associated with children’s lean mass (P &amp;lt; 0.05) and adiposity (fat mass adjusted for lean mass; P &amp;lt; 0.05). The association between maternal glucose and children’s adiposity was independent of children’s REE, percent of time spent physically active, and energy intake (P &amp;lt; 0.001). CONCLUSIONS Intrauterine exposure to relatively high maternal glucose is associated with greater lean mass and adiposity among prepubertal offspring. Further research is needed to examine the mechanisms by which maternal glucose concentrations during pregnancy influence children’s body composition.
Measurement of MMP Activity in Synovial Fluid in Cases of Osteoarthritis and Acute Inflammatory Conditions of the Knee Joints Using a Fluorogenic Peptide Probe-Immobilized Diagnostic Kit
Authors: Ju Hee Ryu, Aeju Lee, Myung Sook Huh, Junuk Chu, Kwangmeyung Kim, Byung-Soo Kim, Kuiwon Choi, Ick Chan Kwon, Jong Woong Park, Inchan Youn
Journal: Theranostics (2012)

A fluorogenic peptide probe-immobilized diagnostic kit was used to analyze MMP activity in the synovial fluids (SFs) from patients with osteoarthritis (OA) and acute inflammatory conditions of the knee joint.The MMP diagnostic kit containing a polymer-conjugated MMP probe immobilized on a 96-well plate was utilized for high-throughput screening of MMP activity in SFs from OA patients (n = 33) and patients with acute inflammatory conditions of the knee joint (n = 5).Compared to SF from OA patients, SF from patients with acute inflammatory conditions of the knee joint presented stronger NIR fluorescent signals. In gelatin zymography, most samples from patients with acute inflammatory conditions of the knee joint also displayed 92 kDa (pro-form) MMP-9 and faint 84 kDa (active form) MMP-9, while SF from OA patients did not display detectable MMP-9 activity .The presence of a strong fluorescence signal from the MMP diagnostic kit corresponded well with patients with acute inflammatory conditions of the knee joint. The results suggest that our MMP diagnostic kit can be useful in differentiation between early stages of OA and acute inflammatory conditions of the knee joint.