tbuckley/cabot-search huggingface dataset:
Comparison of reports on lung function tests made by chest physicians with those made by a simple computer program.
Authors: D M Geddes, M Green, P A Emerson
Journal: Thorax (1978)

The numerical results of 60 sets of pulmonary function tests were submitted to five consultant chest physicians for independent reporting. The chest physicians' reports were compared with the reports generated by the on-line computer reporting system in routine use in the pulmonary function laboratory at Westminster Hospital. There was good agreement between the reports of the chest physicians among themselves and with the computer. The individual reports were compared with the consensus opinions of the physicians and the computer. The computer's decisions differed from the consensus opinion in 4.6% of instances. The comparable figures for the five physicians were respectively 2.9%, 2.9%, 2.9%, 4.0%, and 4.6%. Decisions differing from the consensus were due to mistakes or actual sustained disagreements of opinion. The physicians made more mistakes than the computer even though they were performing under test conditions. They made up for this, however, by producing fewer genuine disagreements from the consensus opinions. It is concluded that in routine day-to-day practice the computer report will be as consistently useful as the chest physicians' reports and more immediately available.
Gut Peptides in the Regulation of Food Intake and Energy Homeostasis
Authors: Kevin G. Murphy, Waljit S. Dhillo, Stephen R. Bloom
Journal: Endocrine Reviews (2006)

Gut hormones signal to the central nervous system to influence energy homeostasis. Evidence supports the existence of a system in the gut that senses the presence of food in the gastrointestinal tract and signals to the brain via neural and endocrine mechanisms to regulate short-term appetite and satiety. Recent evidence has shown that specific gut hormones administered at physiological or pathophysiological concentrations can influence appetite in rodents and humans. Gut hormones therefore have an important physiological role in postprandial satiety, and gut hormone signaling systems represent important pharmaceutical targets for potential antiobesity therapies. Our laboratory investigates the role of gut hormones in energy homeostasis and has a particular interest in this field of translational research. In this review we describe our initial studies and the results of more recent investigations into the effects of the gastric hormone ghrelin and the intestinal hormones peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin on energy homeostasis. We also speculate on the role of gut hormones in the future treatment of obesity.
Novel and Conventional Receptors for Ghrelin, Desacyl-Ghrelin, and Pharmacologically Related Compounds
Authors: Brid Callaghan, John B. Furness
Journal: Pharmacological Reviews (2014)

The only molecularly identified ghrelin receptor is the growth hormone secretagogue receptor GHSR1a. Its natural ligand, ghrelin, is an acylated peptide whose unacylated counterpart (UAG) is almost inactive at GHSR1a. A truncated, nonfunctional receptor, GHSR1b, derives from the same gene. We have critically evaluated evidence for effects of ghrelin receptor ligands that are not consistent with actions at GHSR1a. Effects of ghrelin are observed in cells or tissues where the expression of GHSR1a is not detectable or after the <i>Ghsr</i> gene has been inactivated. In several, effects of ghrelin are mimicked by UAG, and ghrelin binding is competitively reduced by UAG. Effects in the absence of GHSR1a and sites at which ghrelin and UAG have similar potency suggest the presence of novel nonspecific ghrelin receptors (ghrelin receptor–like receptors [GRLRs]). A third class of receptor, the UAG receptors, at which UAG, but not ghrelin, is an agonist has been proposed. None of the novel receptors, with the exception of the glycoprotein CD36, which accounts for ghrelin action at a limited number of sites, have been identified. GHSR1a and GHSR1b combine with other G protein–coupled receptors to form heterodimers, whose pharmacologies differ from their components. Thus, it is feasible some GRLRs and some UAG receptors are heterodimers. Effects mediated through GRLRs or UAG receptors include adipocyte lipid accumulation, myoblast differentiation, osteoblast proliferation, insulin release, cardioprotection, coronary artery constriction, vascular endothelial cell proliferation, and tumor cell proliferation. The molecular identification and pharmacologic characterization of novel ghrelin receptors are thus important objectives.
Correlations Between Fractional Flow Reserve and Intravascular Ultrasound in Patients With an Ambiguous Left Main Coronary Artery Stenosis
Authors: Venu Jasti, Eugen Ivan, Venkata Yalamanchili, Nattawut Wongpraparut, Massoud A. Leesar
Journal: Circulation (2004)

Intravascular ultrasound (IVUS) is being used to assess the significance of a left main coronary artery stenosis (LMCS). However, the cutoff values of IVUS parameters at which to predict a fractional flow reserve (FFR) of 0.75 are unknown.In 55 patients with an angiographically ambiguous LMCS, a pressure guidewire was used to calculate FFR, and IVUS parameters were calculated after automatic pullback. FFR averaged 0.86+/-0.13 (range, 0.55 to 1.0). IVUS minimum lumen diameter (MLD), minimum lumen area (MLA), cross-sectional narrowing (CSN), and area stenosis (AS) were 3.8+/-0.61 mm, 7.65+/-2.9 mm2, 59+/-13%, and 47+/-19%, respectively. Regression analysis demonstrated strong correlations between FFR and MLD (r=0.79, P<0.0001) as well as between FFR and MLA (r=0.74, P<0.0001). There were inverse, moderate correlations between FFR and CSN (r=0.69, P<0.0001), followed by those between FFR and AS (r=0.54, P<0.0001). Compared with FFR as the "gold standard," an MLD of 2.8 mm had the highest sensitivity and specificity (93% and 98%, respectively) for determining the significance of an LMCS, followed by an MLA of 5.9 mm2 (93% and 95%, respectively). Based on an FFR <0.75 and an FFR > or =0.75, the 38-month survival and event-free survival estimates (EFSEs) were both 100% and 100% versus 90%, respectively (P=NS).We conclude that (1) an IVUS MLD and MLA of 2.8 mm and 5.9 mm2, respectively, strongly predict the physiological significance of an LMCS and (2) among patients with an LMCS, an FFR of 0.75 is a strong predictor of survival and EFSE.
The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-β signaling
Authors: Douglas S. Micalizzi, Kimberly L. Christensen, Paul Jedlicka, Ricardo D. Coletta, Anna E. Barón, J. Chuck Harrell, Kathryn B. Horwitz, Dean Billheimer, Karen A. Heichman, Alana L. Welm, William P. Schiemann, Heide L. Ford
Journal: Journal of Clinical Investigation (2009)

Inappropriate activation of developmental pathways is a well-recognized tumor-promoting mechanism. Here we show that overexpression of the homeoprotein Six1, normally a developmentally restricted transcriptional regulator, increases TGF-β signaling in human breast cancer cells and induces an epithelial-mesenchymal transition (EMT) that is in part dependent on its ability to increase TGF-β signaling. TGF-β signaling and EMT have been implicated in metastatic dissemination of carcinoma. Accordingly, we used spontaneous and experimental metastasis mouse models to demonstrate that Six1 overexpression promotes breast cancer metastasis. In addition, we show that, like its induction of EMT, Six1-induced experimental metastasis is dependent on its ability to activate TGF-β signaling. Importantly, in human breast cancers Six1 correlated with nuclear Smad3 and thus increased TGF-β signaling. Further, breast cancer patients whose tumors overexpressed Six1 had a shortened time to relapse and metastasis and an overall decrease in survival. Finally, we show that the effects of Six1 on tumor progression likely extend beyond breast cancer, since its overexpression correlated with adverse outcomes in numerous other cancers including brain, cervical, prostate, colon, kidney, and liver. Our findings indicate that Six1, acting through TGF-β signaling and EMT, is a powerful and global promoter of cancer metastasis.
Adolescents at Risk for MODY3 Diabetes Prefer Genetic Testing Before Adulthood
Authors: Brita Liljeström, Tiinamaija Tuomi, Bo Isomaa, Leena Sarelin, Katja Aktan-Collan, Helena Kääriäinen
Journal: Diabetes Care (2007)

Mutations in the hepatocyte nuclear factor (HNF)-1α gene cause an autosomally, dominantly inherited form of diabetes, maturity-onset diabetes of the young (MODY) type 3, which is characterized by poor insulin secretion in response to glucose together with good sensitivity to insulin and sulfonylurea medication and low renal threshold for glucose (1). The lifetime risk of diabetes may be as high as 95% for individuals carrying the most common Pro291fsinsC mutation. Glucose tolerance deteriorates in most cases during the pubertal years (2–5). However, because of fasting normoglycemia, clinical diagnosis is often delayed despite high postprandial glucose concentrations and an increased A1C value. Diabetes complications are common, and proliferative retinopathy has been detected already at diagnosis of diabetes in a 19-year-old carrier (6). On the other hand, while the incidence of diabetes among mutation carriers steeply increases in puberty, at least 20% remain nondiabetic until their 30s (2,4,5). Abnormal glucose tolerance in subjects at risk for MODY3 can be diagnosed with an oral glucose tolerance test. Urine glucose analysis after a large oral glucose load has also been advocated as a noninvasive screening tool in young children (7). Although an aberrant result from these tests has diagnostic value for diabetes and a certain predictive value in identification of probable carriers, they are not specific for MODY, and a normal result cannot exclude future risk. A genetic test seems to be warranted before adulthood, either to confirm carrier status in these prescreened subjects or in all at-risk subjects. A predictive test, whether a clinical or specific gene …
Assessing Susceptibility from Early-Life Exposure to Carcinogens
Authors: Hugh A. Barton, V. James Cogliano, Lynn Flowers, Larry Valcovic, R. Woodrow Setzer, Tracey J. Woodruff
Journal: Environmental Health Perspectives (2005)

Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6-8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033-0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action.
Chest CT screening of asbestos exposed workers in the Arsenal of Brest: Prevalence of asbestos related abnormalities, and incidental findings
Authors: Anne Pégorié, Nicolas Paleiron, Thomas Erauso, Cecile Tromeur, Sophie Herry, Yvan Bec, Bertrand Bouard, Frédéric Grassin, Michel André
Journal: European Respiratory Journal (2011)

Introduction:  Chest CT screening is part of the recommendations of the French medical surveillance program of asbestos exposed workers, and seems to have shortened the delay in the diagnosis of asbestos related diseases, yet conversely to have increased the number of complementary examinations due to incidental findings.   Aims and objectives:  The aims of the study were to identify, lung lesions and incidental findings discovered during chest CT screening of asbestos exposed workers, assess the number of lesions considered to be professional diseases, and assess the benefits of incidental findings.The impact of tobacco smoking and the level of exposure were assessed.   Methods:  It is a retrospective, analytical study on medical records and chest CT scans of 339 asbestos exposed workers who underwent a first chest CT scan between January 2006 and June 2008, indicated by the health department of Brest military arsenal.   Results:  22% had normal chest CT scans. 54% had pulmonary nodules of which two proved to be malignant. 8.8% had pleural plaques. 3% had dense sub pleural lines. Smokers have twice as many lesions as nonsmokers. No significant difference was shown between patients with different levels of asbestos exposure. On the whole, 9.4% of the images could be related to asbestos exposure. Findings were incidental in 87.6% of cases. They were considered clinically significant in 6 cases.   Conclusion:  The diagnosis of few asbestos related lesions and conversely a large amount of incidental findings raises the question of the benefits of a large scale screening. Indeed, the study highlighted more of a personal, than a medical benefit.
High Tumor Metabolic Activity as Measured by Fluorodeoxyglucose Positron Emission Tomography Is Associated with Poor Prognosis in Limited and Extensive Stage Small-Cell Lung Cancer
Authors: Young Joo Lee, Arthur Cho, Byoung Chul Cho, Mijin Yun, Se Kyu Kim, Joon Chang, Jin Wook Moon, In Kyu Park, Hye Jin Choi, Joo-Hang Kim
Journal: Clinical Cancer Research (2009)

We investigated the prognostic effect of incorporating metabolic assessment by (18)F-fluoro-2-deoxyglucose uptake on positron emission tomography/computed tomography ((18)F-FDG-PET/CT) into a conventional staging system in small-cell lung cancer (SCLC).Seventy-six consecutive patients with pathologically proven SCLC were enrolled. All patients underwent standard treatment after pretreatment (18)F-FDG-PET/CT scanning. The mean values of maximal standardized uptake values (meanSUV(max)) of the malignant lesions upon (18)F-FDG-PET/CT were calculated. The Cox proportional hazards model was used with performance status, lactate dehydrogenase, stage, and meanSUV(max).Patients with high meanSUV(max) were significantly related with the established poor prognostic factors, such as higher lactate dehydrogenase (P = 0.04) and extensive disease (ED; P = 0.01). Furthermore, in multivariate analysis, patients with high meanSUV(max) were associated with poor survival outcomes compared with patients with low meanSUV(max) [adjusted hazard ratio, 3.74; 95% confidence interval (95% CI), 1.67-8.37; P = 0.001, for death and adjusted hazard ratio, 2.25; 95% CI, 1.21-4.17; P = 0.01 for recurrence/progression]. In subgroup analysis, limited disease (LD) with high meanSUV(max) showed significantly shorter overall survival than LD with low meanSUV(max) [high versus low meanSUV(max), 20.1 months (95% CI, 7.9-23.2) versus 35.3 months (95% CI, 27.6-42.9); P = 0.02]. ED with high meanSUV(max) had significantly shorter overall survival than ED with low meanSUV(max) [high versus low meanSUV(max), 9.5 months (95% CI, 4.9-13.9) versus 17.7 months (95% CI, 12.0-20.1); P = 0.007]. These findings were replicated in progression-free survival analysis.In SCLC, tumor metabolic activity as assessed by FDG-PET is a significant prognostic factor and identifies subgroups of patients at higher risk of death in both LD and ED SCLC.
Research on products such as artificial turf is potentially exposed to the same types of industry bias as research on pharmaceuticals
Authors: John Orchard
Journal: British Journal of Sports Medicine (2013)

Imagine your surprise if you were walking through a gardening store and saw a packet of perennial ryegrass seed with the following notification label: “This product has been specifically designed to provide the safest playing surface for football and to protect the knees of young athletes.” Interestingly, there are scientific data to back up that claim.1 The surprise would come because such a claim would be unexpected. Nobody owns a patent for ryegrass ( Lolium perenne is a naturally occurring species), and so there is little commercial benefit in lobbying to claim that it is a safer product.

By contrast, it is not much of a surprise to click on a webpage such as http://www.fieldturf.com/en/fieldturf-difference/proven-safety and find claims that a proprietary artificial turf system reduces injuries. A for-profit company is very interested in promoting scientific data which suggest that their product reduces injury and is equally interested in arguing against any data otherwise. On the FieldTurf ‘Proven safety’ webpage, data are presented from two studies that claim to be ‘independent’ and purport to show the superior safety record of the product compared to natural grass.2 ,3 The webpage does not mention that FieldTurf funded both these ‘independent’ studies. This does not imply that the data from these studies are incorrect, but that the study should be read in the context that it is actually not independent and therefore potentially not free from …
Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic transplantation
Authors: Pieternella S. in `t Anker, Sicco A. Scherjon, Carin Kleijburg-van der Keur, Willy A. Noort, Frans H. J. Claas, Roelof Willemze, Willem E. Fibbe, Humphrey H. H. Kanhai
Journal: Blood (2003)
The Clinical Value of Phonocardiography
Authors: HOWARD B. SPRAGUE, PATRICK A. ONGLEY
Journal: Circulation (1954)

A SCULTATION of the heart is an art in which the conclusions of the observer depend upon acuity of hearing, sense of timing, and appreciation of tonal quality of complex transient noises.These noises are often near the lower limit of audibility in respect to intensity and also frequency.
Phenobarbital-Induced Alterations in Vitamin D Metabolism
Authors: T. J. Hahn, S. J. Birge, C. R. Scharp, L. V. Avioli
Journal: Journal of Clinical Investigation (1972)

The metabolic fate of intravenously injected vitamin D3-1,2-3H (D3-3H) was studied in two normal individuals on chronic phenobarbital therapy. Silicic acid column chromatography of lipid-soluble plasma extracts obtained serially for 96 hr after D3-3H injection demonstrated a decreased plasma D3-3H half-life and increased conversion to more polar metabolites. The polar metabolites formed included several with chromatographic mobility similar to known biologically inactive vitamin D metabolites and one with chromatographic mobility identical to 25-hydroxycholecalciferol. Disappearance of this latter material was also accelerated. A child with rickets and a normal volunteer studied before and after a 2 wk course of phenobarbital therapy demonstrated similar alterations in D3-3H metabolism. When liver microsomes from 3-wk-old Sprague-Dawley rats treated with phenobarbital were incubated with D3-3H, polar metabolites were produced with chromatographic mobility similar to the plasma D3-3H metabolites from phenobarbital-treated humans. Similar incubations employing 25-hydroxy-cholecalciferol-26-27-3H as the substrate also demonstrated an increased conversion to polar metabolites. The data suggest that the reported increased incidence of osteomalacia observed in patients on chronic anticonvulsant therapy may be the result of an accelerated conversion of vitamin D and its active metabolite, 25-hydroxycholecalciferol, to polar metabolites by druginduced liver microsomal enzymes.
Ischemic preconditioning and glucose metabolism during low-flow ischemia: Role of the adenosine A1 receptor
Authors: R de Jonge
Journal: Cardiovascular Research (1999)

Glycolysis-from-glycose may be more beneficial than glycogenolysis in protecting hearts against ischemia. We tested the hypothesis that ischemic preconditioning is mediated by increased exogenous glucose use during low-flow ischemia, an effect triggered by adenosine A1 receptor activation.Langendorff rat hearts were subjected to 25 min low-flow ischemia (0.6 ml/min) and 30 min reperfusion. Prior to underperfusion, hearts (n = 6 per group) were subjected to two cycles of either preconditioning ischemia (PC), infusion of the adenosine A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 0.25 mumol/l), or PC in the presence of the adenosine antagonist 8-(p-sulfophenyl)theophylline (SPT; 50 mumol/l). Glycolysis-from-glucose during underperfusion was measured using D-[2-3H]glucose.At the end of reperfusion, recovery of rate-force product was enhanced in the PC and CCPA groups (62 and 67% of preischemic value) compared to the ischemic control hearts (IC, 32%; P < 0.05), whereas protection was abolished in the SPT hearts (20%; P < 0.05 vs. PC). PC improved total glycolysis-from-glucose during underperfusion by 31% (P < 0.05 vs. IC); SPT abolished this increase. CCPA reduced total lactate release and glucose uptake during ischemia by 47% and 61%, respectively (P < 0.05 vs. IC). Abolishment of the preconditioning-associated increase in glucose uptake during underperfusion, by switching to a low glucose buffer, resulted in a loss of functional protection.This study strongly suggests that increased exogenous glucose utilization during low-flow ischemia mediates ischemic preconditioning without increasing total anaerobic glycolytic flux. Although adenosine A1 receptor activation reduces ischemic injury, it does not facilitate the increased glucose uptake observed with ischemic preconditioning, suggesting a different mechanism of protection.