tbuckley/cabot-search huggingface dataset:
Studies of acid exposure immediately above the gastro-oesophageal squamocolumnar junction: evidence of short segment reflux
Authors: J Fletcher
Journal: Gut (2004)

Oesophageal pH is conventionally recorded from a point 5 cm above the lower oesophageal sphincter. However, the mucosal changes of reflux oesophagitis and intestinal metaplasia tend to affect the segment of oesophagus distal to this and close to the squamocolumnar junction. This study set out to investigate oesophageal acid exposure of squamous mucosa close to the squamocolumnar junction.Dual channel 24 hour pH monitoring was carried out in 11 patients with endoscopy negative dyspepsia and no evidence of gastro-oesophageal reflux by conventional oesophageal pH metry. Oesophageal pH was recorded from electrodes positioned 5 mm and 55 mm proximal to the squamocolumnar junction. A novel technique was developed using metal clips to secure the pH catheter to the oesophageal mucosa and maintain these electrode positions. Oesophageal manometry indicated that the distal electrode was within the high pressure zone of the lower oesophageal sphincter.We found that 24 hour oesophageal acid exposure (per cent time pH <4) was greater 5 mm above the squamocolumnar junction compared with the conventional position 5 cm more proximal (11.7% v 1.8%; p<0.001). The greater acid exposure at the distal versus the conventional site was apparent in both the upright (12.7% v 2.3%) and supine (10.5% v 1.3%) positions, as well as during preprandial (14.2% v 1.6%) and postprandial (21.8% v 2.8%) periods (p<0.001 for each). The number of reflux events recorded close to the squamocolumnar junction was also higher than at the conventional position (168 v 33; p<0.001). There was no correlation between acid exposure at the two sites.The squamous mucosa of the most distal oesophagus is exposed to substantial acidic reflux, even in patients without evidence of conventional reflux disease. This short segment reflux may explain the high incidence of metaplasia and neoplasia at the gastro-oesophageal junction.
Increased inflammatory markers in the exhaled breath condensate of cigarette smokers
Authors: G.E. Carpagnano, S.A. Kharitonov, M.P. Foschino-Barbaro, O. Resta, E. Gramiccioni, P.J. Barnes
Journal: European Respiratory Journal (2003)

Cigarette smoking induces an inflammatory response in the airways that may play a key role in the pathogenesis of chronic obstructive pulmonary disease. Noninvasive markers of inflammation may, therefore, be useful in monitoring the airways of smokers as well as in the screening of subjects at high risk of developing airway obstruction. The aim of the present study was to determine whether the concentrations of the pro-inflammatory cytokine, interleukin (IL)-6, is increased in the exhaled breath condensate of smokers and whether the number of cigarettes smoked has any influence on the exhaled concentrations. The possibility that exhaled IL-6 levels are related to exhaled carbon monoxide (CO) and lung function has also been explored. Another inflammatory marker, leukotriene (LT), was also measured. Twenty-one smokers (39±7 yrs, 13 male) and 14 nonsmokers (45±6 yrs, eight male) were recruited. IL-6 and LTB 4 levels in the breath condensate were measured with an immunoassay kit and exhaled CO examined by means of a modified electrochemical sensor. Higher IL-6 and exhaled CO concentrations were found in current smokers (5.6±1.4 pg·mL −1 and 16.7±5.5 parts per million (ppm)) than in nonsmokers (2.6±0.2 pg·mL −1 and 2.1±0.6 ppm). Elevated concentrations of LTB 4 were also observed in smokers compared to nonsmokers (9.4±0.4 pg·mL −1 versus 6.1±0.3 pg·mL −1 ). In addition, there was a correlation between IL-6 concentrations, the number of cigarettes smoked per day, exhaled CO, LTB 4 and lung function. Exhaled interleukin-6 and leukotriene B 4 levels may be useful noninvasive markers of airway inflammation in cigarette smokers.
Ganglioside GD2 identifies breast cancer stem cells and promotes tumorigenesis
Authors: Venkata Lokesh Battula, Yuexi Shi, Kurt W. Evans, Rui-Yu Wang, Erika L. Spaeth, Rodrigo O. Jacamo, Rudy Guerra, Aysegul A. Sahin, Frank C. Marini, Gabriel Hortobagyi, Sendurai A. Mani, Michael Andreeff
Journal: Journal of Clinical Investigation (2012)

Cancer stem cells (CSCs) are a small subpopulation of cancer cells that have increased resistance to conventional therapies and are capable of establishing metastasis. However, only a few biomarkers of CSCs have been identified. Here, we report that ganglioside GD2 (a glycosphingolipid) identifies a small fraction of cells in human breast cancer cell lines and patient samples that are capable of forming mammospheres and initiating tumors with as few as 10 GD2+ cells. In addition, the majority of GD2+ cells are also CD44hiCD24lo, the previously established CSC-associated cell surface phenotype. Gene expression analysis revealed that GD3 synthase (GD3S) is highly expressed in GD2+ as well as in CD44hiCD24lo cells and that interference with GD3S expression, either by shRNA or using a pharmacological inhibitor, reduced the CSC population and CSC-associated properties. GD3S knockdown completely abrogated tumor formation in vivo. Also, induction of epithelial-mesenchymal transition (EMT) in transformed human mammary epithelial cells (HMLER cells) dramatically increased GD2 as well as GD3S expression in these cells, suggesting a role of EMT in the origin of GD2+ breast CSCs. In summary, we identified GD2 as a new CSC-specific cell surface marker and GD3S as a potential therapeutic target for CSCs, with the possibility of improving survival and cure rates in patients with breast cancer.
Left Ventricular Versus Simultaneous Biventricular Pacing in Patients With Heart Failure and a QRS Complex ≥120 Milliseconds
Authors: Bernard Thibault, Anique Ducharme, François Harel, Michel White, Eileen O'Meara, Marie-Claude Guertin, Joel Lavoie, Nancy Frasure-Smith, Marc Dubuc, Peter Guerra, Laurent Macle, Léna Rivard, Denis Roy, Mario Talajic, Paul Khairy
Journal: Circulation (2011)

Background— Left ventricular (LV) pacing alone may theoretically avoid deleterious effects of right ventricular pacing. Methods and Results— In a multicenter, double-blind, crossover trial, we compared the effects of LV and biventricular (BiV) pacing on exercise tolerance and LV remodeling in patients with an LV ejection fraction ≤35%, QRS ≥120 milliseconds, and symptoms of heart failure. A total of 211 patients were recruited from 11 centers. After a run-in period of 2 to 8 weeks, 121 qualifying patients were randomized to LV followed by BiV pacing or vice versa for consecutive 6-month periods. The greatest improvement in New York Heart Association class and 6-minute walk test occurred during the run-in phase before randomization. Exercise duration at 75% of peak V o 2 (primary outcome) increased from 9.3±6.4 to 14.0±11.9 and 14.3±12.5 minutes with LV and BiV pacing, respectively, with no difference between groups ( P =0.4327). LV ejection fraction improved from 24.4±6.3% to 31.9±10.8% and 30.9±9.8% with LV and BiV pacing, respectively, with no difference between groups ( P =0.4530). Reductions in LV end-systolic volume were likewise similar ( P =0.6788). The proportion of clinical responders (≥20% increase in exercise duration) to LV and BiV pacing was 48.0% and 55.1% ( P =0.1615). Positive remodeling responses (≥15% reduction in LV end-systolic volume) were observed in 46.7% and 55.4% ( P =0.0881). Overall, 30.6% of LV nonresponders improved with BiV and 17.1% of BiV nonresponders improved with LV pacing. Conclusion— LV pacing is not superior to BiV pacing. However, nonresponders to BiV pacing may respond favorably to LV pacing, suggesting a potential role as tiered therapy. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00901212.
Bile Acid-Dependent Secretion of Alkaline Phosphatase in Rat Bile
Authors: David E. Hatoff, William G. M. Hardison
Journal: Hepatology (2007)

The role of bile acids in the biliary secretion of alkaline phosphatase was studied. Rats with external bile fistulae were drained for 4 hr. After 2 hr, bile acid secretion fell progressively. Alkaline phosphatase secretion also decreased progressively during the period of drainage, suggesting that secretion of the two components was related. Each rat was then given an i.v. infusion of the taurine conjugate of either cholate, chenodeoxycholate, or ursodeoxycholate. Alkaline phosphatase secretion increased in a dose-dependent manner as bile acid secretion was varied over and beyond the physiologic range. Each bile acid affected alkaline phosphatase secretion differently: given at 0.5 mumoles per min per 100 gm, tauroursodeoxycholate caused a 3-fold, taurocholate a 14-fold, and taurochenodeoxycholate a 75-fold increase in enzyme secretion. To determine if these findings might represent elution of canalicular enzyme by bile acids, isolated liver surface membranes were incubated with the bile acids. Like the findings in vivo, taurochenodeoxycholate was strongest and tauroursodeoxycholate weakest in removing alkaline phosphatase from the membrane. Differential centrifugation of liver surface membranes after exposure to bile acids and ultracentrifugation of bile showed that more than half of the enzyme released by the action of bile acids did not sediment at 100,000 g and, thus, could be considered soluble. These results document bile acid-dependent secretion of alkaline phosphatase in rat bile and suggest that the process involves solubilization of both membrane fragments and free enzyme from membranes lining the biliary space.
Outpatient liver biopsy: a prospective evaluation of 500 cases
Authors: P Beddy, I L Lyburn, T Geoghegan, O Buckley, A R Buckley, W C Torreggiani
Journal: Gut (2006)

Percutaneous core liver biopsy plays an important role in the management of parenchymal liver disease in establishing diagnosis, evaluating prognosis and monitoring the effect of therapy. Despite the first biopsy been carried out over 100 years ago, debate surrounds best practice.

Day case liver biopsy has become increasingly popular and has not been shown to be associated with increased complications.1,2 Under most day case regimens, patients are observed for up to six hours post biopsy but the majority of complications occur within the first hour post procedure and studies have suggested that the observation period may be reduced from the standard 4–6 h.3–5

Our study prospectively evaluated short stay (1 hour observation) liver biopsy over a 3 …
Validation of a Self-Administered, Computerized Tool for Collecting and Displaying the Family History of Cancer
Authors: Louise S. Acheson, Stephen J. Zyzanski, Kurt C. Stange, Amy Deptowicz, Georgia L. Wiesner
Journal: Journal of Clinical Oncology (2006)

A detailed family history is important for cancer risk assessment, but obtaining it is time consuming and infrequently accomplished in practice. The Genetic Risk Easy Assessment Tool (GREAT) conducts a computer-administered family history interview and immediately generates a pedigree diagram in digital form. The purpose of this study was to validate family cancer histories produced by patients using the computer tool in comparison with pedigrees made by genetic counselors.Patients scheduled for genetics consultation recorded their family histories using the GREAT, separate from their genetic counseling session. The presence of each relative; presence, type, and age at diagnosis of cancers; and cancer geneticist's risk assessment were compared for 120 pairs of pedigrees produced by counselors versus computer tool.The automated telephone interview took a mean of 33.5 minutes and was highly acceptable to respondents. Ninety-four percent of first-degree relatives, 67% of second-degree relatives, and 38% of third-degree relatives were identical on paired pedigrees; computer-generated pedigrees included additional relatives. Sixty-three percent of all cancers were identified by both family histories, with 90% agreement on the type of cancer. There was very good agreement (kappa = 0.70; correlation = 0.77) between the geneticist's breast cancer risk assessments based on computer versus counselors' pedigrees. In a subsample of 61 users, test-retest reliability for the computer-administered questionnaire was high (phi = 0.94 for cancers in first-degree and phi = 0.91 in second-degree relatives).The GREAT computer-administered questionnaire provides an acceptable, reliable, and valid way of collecting an unverified but extensive family history of cancer and displaying it as a pedigree, in an entirely automated process.
Arterial Stiffness Is Inversely Related to Plasma Adiponectin Levels in Young Normotensive Patients With Type 1 Diabetes
Authors: Afroditi Tsiakou, Stavros Liatis, Kleopatra Alexiadou, Evanthia Diakoumopoulou, Konstantinos Makrilakis, Nicholas Tentolouris, Despoina Kyriaki, Nicholas Katsilambros
Journal: Diabetes Care (2012)

OBJECTIVE This study investigated the association between arterial stiffness and plasma adiponectin in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Participants were normotensive patients with type 1 diabetes who were up to age 40 years. Subjects on statins with macrovascular disease or overt nephropathy were excluded. Large artery stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV), whereas plasma adiponectin was measured by radioimmunoassay. RESULTS Data from 80 patients (age 27.1 ± 6.1 years, BMI 24.2 ± 3.1 kg/m(2), HbA(1c) 7.5 ± 1.6%, 39 men, adiponectin 13.9 ± 6.7 μg/mL, and PWV 5.6 ± 0.9 m/s) were analyzed. Log adiponectin inversely correlated with age-adjusted PWV (r = -0.291, P = 0.009) and waist circumference (r = -0.427, P < 0.001). In a fully adjusted model, age, expiration/inspiration index, and log adiponectin were independently associated with PWV, explaining 39.6% of its variance. CONCLUSIONS Arterial stiffness is inversely related to adiponectin concentration in young patients with type 1 diabetes without major complications.
Screening for Coronary Artery Disease After Mediastinal Irradiation for Hodgkin's Disease
Authors: Paul A. Heidenreich, Ingela Schnittger, H. William Strauss, Randall H. Vagelos, Byron K. Lee, Carol S. Mariscal, David J. Tate, Sandra J. Horning, Richard T. Hoppe, Steven L. Hancock
Journal: Journal of Clinical Oncology (2006)

Purpose Incidental cardiac irradiation during treatment of thoracic neoplasms has increased risks for subsequent acute myocardial infarction or sudden cardiac death. Identifying patients who have a high risk for a coronary event may decrease morbidity and mortality. The objective of this study was to evaluate whether stress imaging can identify severe, unsuspected coronary stenoses in patients who had prior mediastinal irradiation for Hodgkin's disease. Patients and Methods We enrolled 294 outpatients observed at a tertiary care cancer treatment center after mediastinal irradiation doses ≥ 35 Gy for Hodgkin's disease who had no known ischemic cardiac disease. Patients underwent stress echocardiography and radionuclide perfusion imaging at one stress session. Coronary angiography was performed at the discretion of the physician. Results Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest, suggesting prior myocardial injury. During stress testing, 42 patients (14%) developed perfusion defects (n = 26), impaired wall motion (n = 8), or both abnormalities (n = 8). Coronary angiography showed stenosis ≥ 50% in 22 patients (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three patients developed coronary events during a median of 6.5 years of follow-up, with 10 acute myocardial infarctions (two fatal). Conclusion Stress-induced signs of ischemia and significant coronary artery disease are highly prevalent after mediastinal irradiation in young patients. Stress testing identifies asymptomatic individuals at high risk for acute myocardial infarction or sudden cardiac death.
Ferritin and Transferrin Are Both Predictive of the Onset of Hyperglycemia in Men and Women Over 3 Years
Authors: Frédéric Fumeron, Franck Péan, Fatti Driss, Beverley Balkau, Jean Tichet, Michel Marre, Bernard Grandchamp
Journal: Diabetes Care (2006)

The aim of the present work was to determine, in a cohort of men and women, whether ferritin and transferrin were associated with glucose metabolism and whether they were predictive of the onset of hyperglycemia (impaired fasting glycemia or type 2 diabetes) after 3 years of follow-up.Among 4,501 subjects from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort, 1,277 subjects (644 men and 633 women) were randomly selected for the analysis of iron biomarkers at baseline and at 3 years. In addition, to determine whether these parameters were relevant to pathological changes, all 231 subjects normoglycemic at baseline and hyperglycemic 3 years later were analyzed for iron biomarkers.At baseline, plasma ferritin concentrations were positively correlated with fasting insulin and fasting glucose in the 1,277 subjects. Although transferrin and ferritin were negatively correlated, transferrin was also positively correlated with fasting insulinemia. Baseline ferritin concentration was an independent predictor of an increase in insulin concentration over a 3-year period (P = 0.002). Further, baseline ferritin and transferrin were independently associated with the onset of hyperglycemia over a 3-year period in the whole population (P < 0.001 for both) and in each sex.Although negatively correlated, both transferrin and ferritin were positively associated with the onset of abnormalities in glucose metabolism in a prospective study. These results further support the hypothesis of a causative role of iron metabolism in the onset of insulin resistance and type 2 diabetes.
Outcome in one-vessel coronary artery disease.
Authors: R M Califf, Y Tomabechi, K L Lee, H Phillips, D B Pryor, F E Harrell, P J Harris, R H Peter, V S Behar, Y Kong, R A Rosati
Journal: Circulation (1983)

We analyzed the clinical outcomes in 688 patients with isolated stenosis of one major coronary artery. The survival rate among patients with disease of the right coronary artery (RCA) was higher than that among patients with left anterior descending (LAD) or left circumflex coronary artery (LCA) disease. The survival rate among patients in all three anatomic subgroups exceeded 90% at 5 years. The presence of a lesion proximal to the first septal perforator of the LAD was associated with decreased survival compared with the presence of a more distal lesion. For the entire group of one-vessel disease patients, total ischemic events (death and nonfatal infarction) occurred at similar rates regardless of the anatomic location of the lesion. Left ventricular ejection fraction was the baseline descriptor most strongly associated with survival, and the characteristics of the angina had the strongest relationship with nonfatal myocardial infarction. No differences in survival or total cardiac event rates were found with surgical or nonsurgical therapy. The relief of angina was superior with surgical therapy, although the majority of nonsurgically treated patients had significant relief of angina. The survival rate of patients with one-vessel coronary disease is excellent, and the risk of nonfatal infarction is low. Clinical strategies for the care of these patients must consider the long-term clinical course of one-vessel coronary disease.
Elastase Release by Transmigrating Neutrophils Deactivates Endothelial-bound SDF-1α and Attenuates Subsequent T Lymphocyte Transendothelial Migration
Authors: Ravi M. Rao, Travis V. Betz, Deanna J. Lamont, Michael B. Kim, Sunil K. Shaw, Richard M. Froio, Françoise Baleux, Fernando Arenzana-Seisdedos, Ronen Alon, Francis W. Luscinskas
Journal: The Journal of Experimental Medicine (2004)

Leukocyte trafficking to sites of inflammation follows a defined temporal pattern, and evidence suggests that initial neutrophil transendothelial migration modifies endothelial cell phenotype. We tested the hypothesis that preconditioning of human umbilical vein endothelial cells (HUVEC) by neutrophils would also modify the subsequent transendothelial migration of T lymphocytes across cytokine-stimulated HUVEC in an in vitro flow assay. Using fluorescence microscopy, preconditioning of HUVEC by neutrophils was observed to significantly reduce the extent of subsequent stromal cell–derived factor-1α (SDF-1α [CXCL12])-mediated T lymphocyte transendothelial migration, without reducing accumulation. In contrast, recruitment of a second wave of neutrophils was unaltered. Conditioned medium harvested after transendothelial migration of neutrophils or supernatants from stimulated neutrophils mediated a similar blocking effect, which was negated using a specific neutrophil elastase inhibitor. Furthermore, T lymphocyte transendothelial migration was inhibited by treatment of HUVEC with purified neutrophil elastase, which selectively cleaved the amino terminus of HUVEC-bound SDF-1α, which is required for its chemotactic activity. The reduction in T lymphocyte transendothelial migration was not observed using a different chemokine, ELC (CCL19), and was not reversed by replenishment of SDF-1α, indicating endothelial retention of the inactivated chemokine. In summary, transmigrating neutrophils secrete localized elastase that is protected from plasma inhibitors, and thereby modulate trafficking of other leukocyte subsets by altering the endothelial-associated chemotactic activities.
Bone Marrow Disorders: The Biological Basis of Clinical Problems
Authors: O'Neill Barrett
Journal: JAMA (1986)

This book is exactly what the title says it is, ie, a discussion of hemopoietic disorders from a biologic perspective. The uniqueness of the book relates to the emphasis placed by the authors on the use of the in vitro cell culture technique in describing normal and abnormal aspects of hemopoiesis. It is decidedly not the usual atlas of bone marrow abnormalities emphasizing morphologic (both light and electron microscopic photographs) and cytochemical descriptors. The absence of color plates underscores this difference. A small number of black-and-white photographs and line drawings accomplish the graphic needs of the text.  The authors have aimed the book at two slightly disparate audiences. They want to provide clinicians with information about the experimental basis for the conditions they treat, emphasizing use of the in vitro cell culture technique. For researchers, they want to provide an outline of practical problems with which the clinician deals. They