tbuckley/cabot-search huggingface dataset:
ChIP'ing the mammalian genome: technical advances and insights into functional elements
Authors: Eleanor Wong, Chia-Lin Wei
Journal: Genome Medicine (2009)

Characterization of the functional components in mammalian genomes depends on our ability to completely elucidate the genetic and epigenetic regulatory networks of chromatin states and nuclear architecture. Such endeavors demand the availability of robust and effective approaches to characterizing protein-DNA associations in their native chromatin environments. Consider able progress has been made through the applica tion of chromatin immunoprecipitation (ChIP) to study chromatin biology in cells. Coupled with genome-wide analyses, ChIP-based assays enable us to take a global, unbiased and comprehensive view of transcriptional control, epigenetic regulation and chromatin structures, with high precision and versatility. The integrated knowledge derived from these studies is used to decipher gene regulatory networks and define genome organization. In this review, we discuss this powerful approach and its current advances. We also explore the possible future developments of ChIP-based approaches to interrogating long-range chromatin interactions and their impact on the mechanisms regulating gene expression.
The association of gastric leptin with oesophageal inflammation and metaplasia
Authors: F Francois, J Roper, A J Goodman, Z Pei, M Ghumman, M Mourad, A Z O. de Perez, G I Perez-Perez, C-H Tseng, M J Blaser
Journal: Gut (2007)

Background: Gastro-oesophageal reflux disease complications may reflect imbalances between protective and injurious factors. Through its effects on cell growth, leptin may influence oesophageal mucosal homeostasis. Aims: To determine whether leptin receptors are present in the oesophagus, and whether serum or gastric leptin levels are associated with oesophageal inflammation and metaplasia. Methods: From patients referred for upper endoscopy, biopsies were obtained from the stomach and distal oesophagus, and serum samples were collected. Patients were classified as having normal, inflamed or Barrett's oesophagus. Quantitative immunohistochemistry was performed on representative sections, and leptin levels in plasma and gastric biopsy samples were determined by specific immunoassay. Results: Of 269 individuals enrolled, 105 were Helicobacter pylori -negative. Of the 88 patients with complete oesophageal biopsies, 44 were normal, 24 were inflamed and 20 were Barrett's oesophagus. Receptors for leptin were highly expressed on oesophageal epithelial cells, with similar density and staining pattern in all three conditions, and plasma and antral leptin levels did not differ significantly. Patients with Barrett's had significantly (p = 0.01) higher fundic leptin levels (median 202 (interquartile range 123–333) pg/mg) compared with normal (126 (78–221) pg/mg) or inflamed (114 (76–195) pg/mg) oesophagus. In multivariate analysis, for every twofold increase in fundic leptin, the odds of having Barrett's was 3.4 times (95% CI 1.5 to 7.6) higher compared with having a normal oesophagus. Conclusions: Leptin receptor expression on oesophageal epithelial cells provides a pathway for leptin-mediated signal transduction. Variation in gastric leptin production could contribute to differential oesophageal healing and metaplasia progression.
Risk Factors for Typhoid and Paratyphoid Fever in Jakarta, Indonesia
Authors: Albert M. Vollaard, Soegianto Ali, Henri A. G. H. van Asten, Suwandhi Widjaja, Leo G. Visser, Charles Surjadi, Jaap T. van Dissel
Journal: JAMA (2004)

The proportion of paratyphoid fever cases to typhoid fever cases may change due to urbanization and increased dependency on food purchased from street vendors. For containment of paratyphoid a different strategy may be needed than for typhoid, because risk factors for disease may not coincide and current typhoid vaccines do not protect against paratyphoid fever.To determine risk factors for typhoid and paratyphoid fever in an endemic area.Community-based case-control study conducted from June 2001 to February 2003 in hospitals and outpatient health centers in Jatinegara district, Jakarta, Indonesia. Enrolled participants were 1019 consecutive patients with fever lasting 3 or more days, from which 69 blood culture-confirmed typhoid cases, 24 confirmed paratyphoid cases, and 289 control patients with fever but without Salmonella bacteremia were interviewed, plus 378 randomly selected community controls.Blood culture-confirmed typhoid or paratyphoid fever; risk factors for both diseases.In 1019 fever patients we identified 88 (9%) Salmonella typhi and 26 (3%) Salmonella paratyphi A infections. Paratyphoid fever among cases was independently associated with consumption of food from street vendors (comparison with community controls: odds ratio [OR], 3.34; 95% confidence interval [CI], 1.41-7.91; with fever controls: OR, 5.17; 95% CI, 2.12-12.60) and flooding (comparison with community controls: OR, 4.52; 95% CI, 1.90-10.73; with fever controls: OR, 3.25; 95% CI, 1.31-8.02). By contrast, independent risk factors for typhoid fever using the community control group were mostly related to the household, ie, to recent typhoid fever in the household (OR, 2.38; 95% CI, 1.03-5.48); no use of soap for handwashing (OR, 1.91; 95% CI, 1.06-3.46); sharing food from the same plate (OR, 1.93; 95% CI, 1.10-3.37), and no toilet in the household (OR, 2.20; 95% CI, 1.06-4.55). Also, typhoid fever was associated with young age in years (OR, 0.96; 95% CI, 0.94-0.98). In comparison with fever controls, risk factors for typhoid fever were use of ice cubes (OR, 2.27; 95% CI, 1.31-3.93) and female sex (OR, 1.79; 95% CI, 1.04-3.06). Fecal contamination of drinking water was not associated with typhoid or paratyphoid fever. We did not detect fecal carriers among food handlers in the households.In Jakarta, typhoid and paratyphoid fever are associated with distinct routes of transmission, with the risk factors for disease either mainly within the household (typhoid) or outside the household (paratyphoid).
INDICATIONS FOR THE INDUCTION OF PREMATURE LABOUR
Authors: H. J. D. Smythe
Journal: BMJ (1931)

_~~~~~~~~~~~~[EIA JOUNAL long a period as the patient could reasonably be asked to remain in the water.On almost every occasion distress was marked not later than forty-five minutes after the commencement.The average loss of weight during each bath amounted to 4j to 5i lb., the minimum being 3 lb.and the maximum 6 lb. 10 oz.By the next morning this loss had sometimes been more-than made up.During the nine months of treatment the patient showed a net gain of 47 oz.(9 st.11 lb.13 oz.to 10 st. 12 oz.), and
Risk Factors for Rifampin-monoresistant Tuberculosis
Authors: LAURIE SANDMAN, NEIL W. SCHLUGER, AMY L. DAVIDOW, STANLEY BONK
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Rifampin is the cornerstone of short-course chemotherapy for the treatment of tuberculosis (TB). Rifampin monoresistance (RMR) is less common than resistance to isoniazid alone or in combination with other antituberculous medications. We conducted a retrospective case-control study to identify risk factors for RMR-TB. Complete records for 21 of a total of 26 RMR patients from 1990 to 1997 were available for review, and were compared with those of 48 patients with drug-susceptible TB, controlling for year of diagnosis. Cases more frequently had a history of TB than did controls (61% versus 22%, p < 0.01), and were more often human immunodeficiency virus (HIV) positive (81% versus 46%, p = 0.02). With control for HIV status, cases were more likely to have extrapulmonary involvement (47.6% versus 11.6%, p = 0.05). Four cases (19%) and one control (2. 1%) died (p = 0.02) during hospitalization. Cases more often had a history of incarceration (71.4% versus 37.5%, p = 0.09). Among the 13 cases with a history of TB, five had evidence of malabsorption (vomiting and/or diarrhea), versus none of the 11 controls with prior TB. These data support the hypothesis that RMR is seen primarily in individuals with a history of TB and who are HIV positive. Cases were frequently noncompliant with previous treatment for TB, had a history of incarceration, and had poor outcomes.
Reply: Rationale for Anticoagulant Therapy of Pulmonary Fibrosis
Authors: Imre Noth, Mitchell A. Olman
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

From the Authors:

We appreciate the insightful letter by Bogatkevich and colleagues, and strongly concur with their conclusions to carefully consider the potential unique antifibrotic effects of inhibiting individual components of the coagulation cascade, especially thrombin. Indeed, the unique effects of individual members of the coagulation cascade, compared with the cascade as a whole, deserve additional respect in light of the unsuccessful AntiCoagulant Effective in Idiopathic Pulmonary Fibrosis (ACE-IPF) trial (1, 2).

At the time of our trial development, we were charged with designing a trial using available, FDA-approved, therapeutic interventions for pathways involved in fibrosis. We believe the ACE trial does demonstrate that the coagulation cascade (or other vitamin K–dependent proteins) plays a role in IPF, in that use of warfarin did lead to worsened outcomes (2). The notion of a more selective blockade of thrombin activity is an attractive idea.

Our understanding of thrombin activity and protease-activated receptor (PAR)-mediated lung inflammation and fibrosis is growing rapidly. The authors of the letter to the editor have contributed significantly to this understanding through their findings that the thrombin inhibitor, dabigatran, has antifibrotic effects on lung fibroblasts and in a murine lung fibrosis model (3, 4). Moreover, Wygrecka and colleagues demonstrate that knockdown of PAR-1 and PAR-3 together, rather than PAR-1 alone, was necessary to inhibit thrombin-mediated epithelial to mesenchymal transition (5). The PARs remain an interesting antifibrotic target, and understanding their complex biological effects may be critical in the selection of a successful therapy. Given the availability of dabigatran etexilate, we would fully support a clinical trial to evaluate its activity. We hope that a validation of the biological effect on the correct target in vivo, would be a key part of any such clinical outcome trial in IPF, so that we can further advance this promising field.
Randomized Phase II/III Trial of Interferon Alfa-2a With and Without 13-<i>cis</i>-Retinoic Acid in Patients With Progressive Metastatic Renal Cell Carcinoma: The European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951)
Authors: Nina Aass, Pieter H.M. De Mulder, Gerald H.J. Mickisch, Peter Mulders, Allan T. van Oosterom, Hein van Poppel, Sophie D. Fossa, Linda de Prijck, Richard J. Sylvester
Journal: Journal of Clinical Oncology (2005)

A randomized phase II/III trial was conducted to determine whether combination treatment with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFN-alpha-2a) was superior to IFN-alpha-2a alone in patients with progressive metastatic renal cell carcinoma.Three hundred twenty patients were randomly assigned to treatment with IFN-alpha-2a plus 13-CRA or to IFN-alpha-2a alone. IFN-alpha-2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU by increments of 3 MU. Patients randomly assigned to combination therapy received oral 13-CRA 1 mg/kg/d plus IFN-alpha-2a.Median time to progression was 5.1 months for patients treated with the combination and 3.4 months for patients on IFN-alpha-2a alone (P = .008). Progression-free survival rates at 6 months were 43% for patients receiving combined therapy and 30% for patients on IFN-alpha-2a, and at 12 months, 27% and 17%, respectively. Median overall survival was 17.3 months for patients on IFN-alpha-2a and 13-CRA, and 13.2 months for patients treated with IFN-alpha-2a (P = .048). Twenty-two percent of the patients receiving the combination stopped treatment due to toxicity, as compared with 16% on IFN-alpha-2a.Progression-free and overall survival for patients with progressive metastatic renal cell carcinoma treated with IFN-alpha-2a plus 13-CRA were significantly longer compared with patients on IFN-alpha-2a alone (P = .007 and P = .048, respectively). Improvement in efficacy in the combination arm was accompanied by increased, though not serious, toxicity.
Quantitative variations of the C3b/C4b receptor (CR1) in human erythrocytes are controlled by genes within the regulator of complement activation (RCA) gene cluster.
Authors: S Rodriguez de Cordoba, P Rubinstein
Journal: The Journal of Experimental Medicine (1986)

The genetic relationships of quantitative and structural variations of the C3b/C4b receptor (CR1) in human erythrocytes have been analyzed in informative families. Our results demonstrate the existence of multiple discrete quantitative variations of CR1 controlled by a locus, C3bRQ, closely linked to the CR1 structural locus, C3bR. Since the amounts of CR1 produced by each C3bR allele are shown to be independently regulated, we propose that a cis-acting genetic mechanism controls the level of expression of the C3bR alleles, and that this quantitative control plays a major, if not the sole, role in determining the total amounts of CR1 on normal human erythrocytes.
Calcium transport properties of cardiac sarcoplasmic reticulum from cardiomyopathic Syrian hamsters (BIO 53.58 and 14.6): evidence for a quantitative defect in dilated myopathic hearts not evident in hypertrophic hearts.
Authors: J T Whitmer, P Kumar, R J Solaro
Journal: Circulation Research (1988)

Calcium uptake was measured in homogenates and microsomal preparations enriched in sarcoplasmic reticulum vesicles isolated from hearts of hypertrophic (BIO 14.6) and dilated (BIO 53.58) cardiomyopathic as well as control (F1B) Syrian hamsters at 3, 7, 9, and 11 months of age. Calcium uptake studies were done using the Millipore filtration technique under conditions known to restrict transport to the sarcoplasmic reticulum. Steady-state calcium uptake capacity was used as a measure of the relative amounts of sarcoplasmic reticulum in homogenates prepared from individual hearts. At 3 months of age, there were no differences in calcium uptake in homogenates from control or myopathic hearts. However, by 9 months, although calcium uptake of homogenates from control and hypertrophic hearts was the same, calcium uptake by homogenates from dilated hearts was significantly depressed both in initial rate and capacity. Similar trends were seen in the microsomal vesicle preparations, but the decrease in calcium uptake in the dilated hearts was significantly lower by 3 months of age. The catalytic activity of the sarcoplasmic reticulum transport enzyme was estimated from the ratio of velocity to capacity, which provides a measure of the fractional rate of filling of the sarcoplasmic reticulum with calcium. The velocity-to-capacity ratios were not different at any of the ages in both the homogenate and microsomal preparations. The results of this study demonstrate that a major defect in the dilated cardiomyopathy may be due to a decrease in the volume or number of sarcoplasmic reticulum calcium transport sites rather than a decrease in specific activity of the transport enzyme.
Factors Involved in Catheter Obstruction During Long-Term Peritoneal Insulin Infusion
Authors: Regine Bousquet-Rouaud, Françoise Castex, Guy Costalat, Madeleine Bastide, Bernard Hedon, Majida Bouanani, Sylvie Jouvert, Jacques Mirouze
Journal: Diabetes Care (1993)

To analyze the efficacy of ECPII and the factors responsible for technical problems often encountered. This treatment has been in use with IDDM patients since 1980.Forty-four IDDM patients were treated by ECPII for 42-78 mo (mean, 53 mo).Glycemic equilibrium was improved during treatment (mean plasma glucose level, 7.6 mM; mean GHb level, 8%). Catheter blockage was the main reason for ECPII failure (74%). Mean catheter survival of each catheter, determined by actuarial analysis, was 11.7 mo and significantly decreased with subsequent implantation. SEM of the catheter tips showed deposits composed of fibrin and cells occluding the inner lumen. Factors such as age, sex, local infection, and low insulin basal rate were not found to have any incidence on the catheter survival. Placement of the catheter in the upper part of the peritoneum, however, increased catheter survival. Anti-insulin antibodies did not seem to be directly involved in blockage.We conclude from this long-term experience that during ECPII, catheter blockage remains the major recurring complication, probably involving a local immune-inflammatory response in the peritoneum.
Keratin-14 Expression in Pneumocytes as a Marker of Lung Regeneration/Repair during Diffuse Alveolar Damage
Authors: Miriam Ficial, Caterina Antonaglia, Marco Chilosi, Mario Santagiuliana, Al-Omoush Tahseen, Davide Confalonieri, Lorenzo Zandonà, Rossana Bussani, Marco Confalonieri
Journal: American Journal of Respiratory and Critical Care Medicine (2014)
Cervical Gland Tuberculosis
Authors: W. G. Sutcliffe
Journal: BMJ (1936)

The pubertal peak in onset of type 1 diabetes occurs earlier in girls than boys. We postulated that this sex difference might be mediated in part by estrogen or by genes regulated by estrogen, such as the interleukin-6 (IL6) gene. Previous studies concerning the role of an estrogen-sensitive single nucleotide polymorphism (SNP) in the IL6 promoter in type 1 diabetes have proved contradictory. We therefore selected a large, genetically homogenous population-based cohort, analyzed by age at onset and sex, to test the hypothesis that the IL6-174G>C SNP affects age at onset of type 1 diabetes in females but not in males. We found that the IL6-174CC genotype was significantly less frequent in females diagnosed after than in those diagnosed before the age of 10 years (19 vs. 13%, P = 0.016). No genotype difference was observed in males stratified for age at onset. Among children diagnosed after age 10, the median age of onset was 11.9 years (intraquartile range 10.7–14.6) in 34 girls homozygous for IL6-174C compared with 13.2 years (11.6–15.4) in 229 girls with other genotypes and 13.5 years (12.0–15.6) in 339 males with any IL6-174 genotype (P = 0.012). These data support the hypothesis that pubertal changes may contribute to accelerated onset of type 1 diabetes in genetically susceptible females. This phenomenon may be orchestrated by the action of estrogen on the IL6 promoter.
Pyridoxal Phosphate and Hepatocyte Growth Factor Prevent Dialysate-Induced Peritoneal Damage
Authors: Sakurako Nakamura, Toshimitsu Niwa
Journal: Journal of the American Society of Nephrology (2004)

Glucose-based peritoneal dialysate (PD) is responsible for increased accumulation of advanced glycation end products (AGE) in the peritoneum of continuous ambulatory peritoneal dialysis patients. Pyridoxal 5'-phosphate (PLP), a derivative of vitamin B(6), protects proteins from glycation. Hepatocyte growth factor (HGF) heals damaged tissues in a reciprocal manner against TGF-beta1. First, with the use of gas chromatography-mass spectrometry, whether PLP traps 3-deoxyglucosone (3DG), a major glucose degradation product in PD, was determined. Then, whether rat peritoneal tissue damages induced by intraperitoneal administration of glucose-based PD is ameliorated by PLP or HGF was examined. In vitro incubation with PLP markedly decreased concentration of 3DG in a dose-dependent manner, demonstrating the 3DG-trapping effect of PLP. The peritoneum of PD-treated rats was significantly thickened compared with that of physiologic saline-treated rats. Both PLP and HGF prevented the thickening of rat peritoneum induced by PD and ameliorated accumulation of AGE and expression of TGF-beta1, vascular endothelial growth factor, and type 1 collagen and a number of blood vessels. Furthermore, expression of HGF was significantly increased in the peritoneum of PLP-treated rats compared with that of PD-treated rats. In conclusion, PLP shows 3DG-trapping effect. PLP and HGF prevented peritoneal thickening; accumulation of AGE; expression of TGF-beta1, vascular endothelial growth factor, and type 1 collagen; and neoangiogenesis in rat peritoneum induced by PD.
Assessing nodules detected in lung cancer screening: the value of positron emission tomography
Authors: Jann Mortensen
Journal: European Respiratory Journal (2015)

Lung cancer is the leading cause of death worldwide. Screening for lung cancer may improve the poor prognosis by detecting the cancer at an early stage where radical surgery still is possible. Several randomised clinical trials using low-dose computed tomography (CT) have been launched in high-risk smokers or former smokers in the USA and Europe [1–3]. The National Lung Screening Trial (NLST) randomised 53 454 subjects to undergo annual CT scans or chest radiographies for 3 years, and demonstrated that overall and lung cancer specific mortality was reduced in the CT arm [1]. For one case of death from lung cancer to be prevented, the number of patients that needed to be screened using CT compared with chest radiography was 320 [3]. The final mortality data testing of >32 000 individuals participating in the seven European randomised lung cancer CT screening trials (EUCT), where the control groups had no chest radiography, is expected in 2015 [2]. PET has the highest accuracy in differential diagnosis of upper lobe, solid >10 mm or partly-solid >15 mm nodules <http://ow.ly/DKaur>
Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459
Authors: D. Singh, P. Cadden, M. Hunter, L. Pearce Collins, M. Perkins, R. Pettipher, E. Townsend, S. Vinall, B. O'Connor
Journal: European Respiratory Journal (2012)

CRTH2 (chemoattractant receptor expressed on T-helper (Th) type 2 cells) is a G-protein-coupled receptor expressed by Th2 lymphocytes and eosinophils that mediates prostaglandin (PG)D<sub>2</sub>-driven chemotaxis. We studied the efficacy of the oral CRTH2 antagonist OC000459 in steroid-naïve asthmatic patients. A randomised, double-blind, placebo-controlled, two-way crossover study of 16 days’ treatment with OC000459 (200 mg twice daily) on the late (LAR) and early (EAR) asthmatic responses to bronchial allergen challenge was conducted, with 16 subjects completing the study. There was a 25.4% (95% CI 5.1–45.6%) reduction in the LAR area under the curve (AUC) for change in forced expiratory volume in 1 s with OC000459 compared with placebo (p=0.018) but no effect on the EAR. Sputum eosinophil counts at 1 day post-allergen challenge were lower after OC000459 treatment (p=0.002). PGD<sub>2</sub>-induced blood eosinophil shape change <i>ex vivo</i> was assessed at day 7 (n=7). The AUC of eosinophil shift for OC000459 was lower than placebo; the mean difference was -33.6% (95% CI -66.8– -0.4%; p=0.048). OC000459 treatment inhibited LAR and post-allergen increase in sputum eosinophils. This CRTH2 antagonist appears to inhibit allergic inflammation in asthma.