tbuckley/cabot-search huggingface dataset:
Intraepithelial airway dendritic cells: a distinct subset of pulmonary dendritic cells obtained by microdissection.
Authors: J L Gong, K M McCarthy, J Telford, T Tamatani, M Miyasaka, E E Schneeberger
Journal: The Journal of Experimental Medicine (1992)

Dendritic cells (DC), in general, and pulmonary DC, in particular, are a heterogeneous population of cells, their phenotype and function being dependent on their anatomic location, their state of activation, and the regulatory effect of locally secreted cytokines. Using a novel microdissection technique, the epithelium from the trachea and entire airway system was harvested, and the contained DC isolated at greater than 90% purity. The phenotype and function of these airway DC (ADC) was compared to DC isolated, at greater than 90% purity, from the parenchyma of the same lung. In contrast to lung DC (LDC), ADC did not express intercellular adhesion molecule 1 (ICAM-1) in situ, the amount of immune associated antigen (Ia) expressed was less (as determined by immunoperoxidase staining and immunopanning), and greater than 50% of ADC displayed Fc receptors (FcR). The majority of LDC were ICAM-1+, less than 5% expressed FcR, and all were intensely Ia+. Airway DC were most numerous in tracheal epithelium, but they were also present in small numbers in the epithelium of the most distal airways. Their numbers increased in all segments of the tracheobronchial epithelium in response to the administration of IFN-gamma. ADC were consistently more effective than LDC in presenting soluble (hen egg lysozyme) and particulate (heat-killed Listeria monocytogenes) antigens to antigen-sensitized T cells. By contrast, LDC were significantly more efficient in stimulating the proliferation of nonsensitized T cells in an autologous mixed leukocyte reaction. These data suggest that in normal animals, intraepithelial DC of airways share many attributes with Langerhans cells of the skin. Interstitial LDC, by contrast, reside in an environment where they may be exposed to a different set of regulatory factors and where they have progressed to a more advanced stage of differentiation than ADC. Both groups of DC are, however, heterogeneous, reflecting the continuous turnover that these cells undergo in the lung.
Regulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors
Authors: N. Marty
Journal: Journal of Clinical Investigation (2005)

Ripglut1;glut2-/- mice have no endogenous glucose transporter type 2 (glut2) gene expression but rescue glucose-regulated insulin secretion. Control of glucagon plasma levels is, however, abnormal, with fed hyperglucagonemia and insensitivity to physiological hypo- or hyperglycemia, indicating that GLUT2-dependent sensors control glucagon secretion. Here, we evaluated whether these sensors were located centrally and whether GLUT2 was expressed in glial cells or in neurons. We showed that ripglut1;glut2-/- mice failed to increase plasma glucagon levels following glucoprivation induced either by i.p. or intracerebroventricular 2-deoxy-D-glucose injections. This was accompanied by failure of 2-deoxy-D-glucose injections to activate c-Fos-like immunoreactivity in the nucleus of the tractus solitarius and the dorsal motor nucleus of the vagus. When glut2 was expressed by transgenesis in glial cells but not in neurons of ripglut1;glut2-/- mice, stimulated glucagon secretion was restored as was c-Fos-like immunoreactive labeling in the brainstem. When ripglut1;glut2-/- mice were backcrossed into the C57BL/6 genetic background, fed plasma glucagon levels were also elevated due to abnormal autonomic input to the alpha cells; glucagon secretion was, however, stimulated by hypoglycemic stimuli to levels similar to those in control mice. These studies identify the existence of central glucose sensors requiring glut2 expression in glial cells and therefore functional coupling between glial cells and neurons. These sensors may be activated at different glycemic levels depending on the genetic background.
Bradykinin Stimulates Tissue Plasminogen Activator Release From Human Forearm Vasculature Through B <sub>2</sub> Receptor–Dependent, NO Synthase–Independent, and Cyclooxygenase-Independent Pathway
Authors: Nancy J. Brown, James V. Gainer, Laine J. Murphey, Douglas E. Vaughan
Journal: Circulation (2000)

Background —Bradykinin stimulates dose-dependent tissue plasminogen activator (tPA) release from human endothelium. Although bradykinin is known to cause vasodilation through B 2 receptor–dependent effects on NO, prostacyclin, and endothelium-derived hyperpolarizing factor production, the mechanism(s) underlying tPA release is unknown. Methods and Results —We measured the effects of intra-arterial bradykinin (100, 200, and 400 ng/min), acetylcholine (15, 30, and 60 μg/min), and nitroprusside (0.8, 1.6, and 3.2 μg/min) on forearm vasodilation and tPA release in healthy volunteers in the presence and absence of (1) the B 2 receptor antagonist HOE 140 (100 μg/kg IV), (2) the NO synthase inhibitor l - N G -monomethyl- l -arginine (L-NMMA, 4 μmol/min intra-arterially), and (3) the cyclooxygenase inhibitor indomethacin (50 mg PO TID). B 2 receptor antagonism attenuated vasodilator ( P =0.004) and tPA ( P =0.043) responses to bradykinin, without attenuating the vasodilator response to nitroprusside ( P =0.36). L-NMMA decreased basal forearm blood flow (from 2.35±0.31 to 1.73±0.22 mL/min per 100 mL, P =0.01) and blunted the vasodilator response to acetylcholine ( P =0.013) and bradykinin ( P =0.07, P =0.038 for forearm vascular resistance) but not that to nitroprusside ( P =0.47). However, there was no effect of L-NMMA on basal ( P =0.7) or bradykinin-stimulated tPA release ( P =0.45). Indomethacin decreased urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F 1α ( P =0.04). The vasodilator response to endothelium-dependent ( P =0.019 for bradykinin) and endothelium-independent ( P =0.019) vasodilators was enhanced during indomethacin administration. In contrast, there was no effect of indomethacin alone ( P =0.99) or indomethacin plus L-NMMA ( P =0.36) on bradykinin-stimulated tPA release. Conclusions —These data indicate that bradykinin stimulates tPA release from human endothelium through a B 2 receptor–dependent, NO synthase–independent, and cyclooxygenase-independent pathway. Bradykinin-stimulated tPA release may represent a marker for the endothelial effects of endothelium-derived hyperpolarizing factor.
Comparing cystic fibrosis outcomes across the pond
Authors: D. C. Taylor-Robinson, M. S. Schechter, R. L. Smyth
Journal: Thorax (2014)

Analysis of registry data has provided key insights into the changing demographics, outcomes and treatments in cystic fibrosis (CF), but few studies have made use of the great potential for cross-country comparisons. The linked study by Goss and colleagues1 in Thorax does just this, using registry data collected in the UK and the USA to compare CF outcomes and use of treatments on opposite sides of the Atlantic. The study certainly makes for uncomfortable reading from a UK perspective, but raises more questions than it addresses. The analysis suggests that the USA does better in terms of lung function in children, and the authors conclude this is due to more intensive treatment in the early years. But is this interpretation correct?

One of the most important findings of the study is the striking gap in mean % predicted FEV1 between the UK and the USA at around 6 years, the age at which lung function can be consistently collected and measured reliably at all care centres. The gap subsequently narrows and disappears by age 30. Overall, children under 12 years of age in the UK had significantly lower lung function by 7.6 percentage points compared with children in the USA. This is a big difference in a study where the large sample sizes mean that the estimations of population level differences are quite precise, even for imprecisely measured outcomes such as % predicted FEV1.2

In these initial attempts to compare data collected in slightly different ways in different countries, it is important to ensure that the comparisons are valid. For example, we must ensure that the findings of this analysis are not biased by the possibility that the samples used in the study are not fully representative of the entire CF populations in their respective countries. Ascertainment …
Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial
Authors: Bojan Cercek, Prediman K Shah, Marko Noc, Doron Zahger, Uwe Zeymer, Shlomi Matetzky, Gerald Maurer, Peter Mahrer
Journal: The Lancet (2003)
Transmission of tuberculosis from smear negative patients: a molecular epidemiology study
Authors: E Hernandez-Garduno
Journal: Thorax (2004)

Background: While smear positive patients with tuberculosis (TB) are considered more infectious than smear negative patients, the latter can also transmit TB. Methods: In a molecular epidemiology study of 791 patients in the Greater Vancouver regional district, the number of episodes of TB transmission from two groups of smear negative clustered patients by RFLP (assumed to be involved in recent transmission) was estimated after assessing for potential bias. Group 1 (n = 79) included patients with pulmonary TB or pulmonary + extrapulmonary disease (PTB or PTB+EPTB); group 2 (n = 129) included all patients in group 1 + extrapulmonary cases alone. Results: In the total sample the mean (SD) age was 51 (21) years, 54.3% were male, and 17.0% of patients were clustered. Compared with smear negative patients, smear positive patients were more likely to be in a cluster (OR = 2.0, 95% CI 1.1 to 3.6) and to have had a history of ethanol abuse (OR = 2.7, 95% CI 1.0 to 6.7), diabetes mellitus (OR = 2.8, 95% CI 1.1 to 7.0), injection drug use (OR = 3.1, 95% CI 1.1 to 8.3), and to have had a previous hospital admission (OR = 8.5, 95% CI 5.1 to 14.0). The proportion of episodes of transmission from smear negative clustered patients ranged from 17.3% to 22.2% in group 1 and from 25% to 41% in group 2. Conclusion: In Greater Vancouver, smear negative cases appear responsible for at least one sixth of culture positive episodes of TB transmission.
THE ANTISTREPTOCOCCAL PROPERTY OF MILK
Authors: Armine T. Wilson, Herman Rosenblum
Journal: The Journal of Experimental Medicine (1952)

The ability of lactenin to prevent the multiplication of group A streptococci when milk becomes contaminated with that organism accounts in part at least, for the infrequency of milk-borne streptococcal epidemics. From epidemiological studies it has been shown that most such epidemics arise from the consumption of raw milk in which streptococci occur as a result of bovine mastitis due to group A streptococcus. Lactenin fails to prevent the establishment of mastitis due to the group A streptococcus because the milk in the cow's udder is at a low oxidation-reduction potential and the lactenin is inactive. Lactenin, being destroyed by temperatures of 80°C. or above, is absent from canned and powdered milk. When the latter have been diluted or reconstituted, they can serve as excellent growth media for group A streptococci, and epidemics have occurred as a result of contamination of milk supplies of those types. The administration of lactenin by mouth or intraperitoneal injection failed to protect mice from peritonitis or subcutaneous infection due to group A streptococcus.
Colorectal Cancer With Mutation in <i>BRAF</i>, <i>KRAS</i>, and Wild-Type With Respect to Both Oncogenes Showing Different Patterns of DNA Methylation
Authors: Takeshi Nagasaka, Hiromi Sasamoto, Kenji Notohara, Harry M. Cullings, Masanori Takeda, Keigo Kimura, Takeshi Kambara, Donald G. MacPhee, Joanne Young, Barbara A. Leggett, Jeremy R. Jass, Noriaki Tanaka, Nagahide Matsubara
Journal: Journal of Clinical Oncology (2004)

Purpose BRAF mutations are common in sporadic colorectal cancers (CRCs) with a DNA mismatch repair (MMR) deficiency that results from promoter methylation of hMLH1, whereas KRAS mutations are common in MMR proficient CRCs associated with promoter methylation of MGMT. The aim of this study was to further investigate the link between genetic alterations in the RAS/RAF/ERK pathway and an underlying epigenetic disorder. Patients and Methods Activating mutations of BRAF and KRAS were identified and correlated with promoter methylation of 11 loci, including MINT1, MINT2, MINT31, CACNA1G, p16 INK4a , p14 ARF , COX2, DAPK, MGMT, and the two regions in hMLH1 in 468 CRCs and matched normal mucosa. Results BRAF V599E mutations were identified in 21 (9%) of 234 CRCs, and KRAS mutations were identified in 72 (31%) of 234 CRCs. Mutations in BRAF and KRAS were never found in the same tumor. CRCs with BRAF mutations showed high-level promoter methylation in multiple loci, with a mean number of methylated loci of 7.2 (95% CI, 6.6 to 7.9) among 11 loci examined (P &lt; .0001). Tumors with KRAS mutations showed low-level promoter methylation, and CRCs with neither mutation showed a weak association with promoter methylation, with an average number of methylated loci of 1.8 (95% CI, 1.5 to 2.1) and 1.0 (95% CI, 0.79 to 1.3), respectively. Conclusion In CRC, the methylation status of multiple promoters can be predicted through knowledge of BRAF and, to a lesser extent, KRAS activating mutations, indicating that these mutations are closely associated with different patterns of DNA hypermethylation. These changes may be important events in colorectal tumorigenesis.
Attributed talent is a powerful myth
Authors: Clemens Tesch-Römer
Journal: Behavioral and Brain Sciences (1998)

Whereas the reality of “innate talent” is questioned by the authors, the role of “attributed talent” is not discussed fully. “Attributed talent” is the imputation of high, not yet unfolded ability to an individual. Only if talent is attributed to a novice will resources be invested in the development of expertise. An alternative for estimating future achievement is discussed.
1342 CHANGE IN SOLUBLE CD163, A MARKER OF ACTIVATED MACROPHAGES, IS ASSOCIATED WITH IMPROVEMENT IN LIVER ENZYMES AND METABOLIC PROFILE IN OBESE CHILDREN DURING LIFESTYLE INTERVENTION
Authors: K. Kazankov, H.J. Moller, A. Lange, N.H. Birkebak, P. Holland- Fischer, J. Solvig, A. Horlyck, K. Kristensen, S. Rittig, H. Vilstrup, H. Gronbak
Journal: Journal of Hepatology (2013)
SURGICAL TREATMENT FOR MIDPORTION ACHILLES TENDINOPATHY- A SYSTEMATIC REVIEW
Authors: Sina David, Tanja Nauk, Heinz Lohrer
Journal: British Journal of Sports Medicine (2013)

Background Purpose of this systematic review was (i) to provide means of judgement to assess the benefits and tradeoffs related with different surgical treatments for midportion Achilles tendinopathy and (ii) to highlight possible alternative treatments for Achilles tendinopathy in cases when conservative treatments fail to reach patient satisfaction. Methods To identify studies about surgical treatment of patients with mid-portion Achilles tendinopathy, MEDLINE, Cochrane Database and Google databases (1945 till November 2012) were searched. After excluding several articles due to our selection criteria, the remaining articles were analyzed and evaluated using the Coleman Methodology Score. Additionally, success rate and the complication rate were determined. Results Seven studies met our inclusion criteria. These reports evaluated five different operative techniques. A total of 353 tendons were treated in 347 patients with open or minimally invasive techniques. The mean patient satisfaction was 71.4% (range 48% to 100%). The mean rate of minor complications was 4.6% (range 0% to 9.5%). The average of major complications was 3.3% (rang 0% to 14%). The studies assessing minimally invasive techniques reported an average success rate of 62% (range 49% to 75%), 2.7%, minor complications (range 0% to 8%), and no major complications. The open invasive procedures show an average success rate of 78% (range 52% to 86%), a minor complication rate of 6% (range 0% to 9.5%), and a major complication rate of 5.8% (range 0% to 12%). Conclusions All investigated operative methods were demonstrated to improve patients's conditions, though success rates varied between operative techniques. The complication rate differs between used techniques. Minimal invasive operative techniques seem to be related with fewer complications but open techniques report on higher success rates. Results vary between subjects according to sex and activity level.
A novel tissue preservation medium for immunoperoxidase staining of skin biopsies
Authors: A. CARMICHAEL, G.R. COGHILL, I.A. CREE, S. GEORGE, J.G. LOWE
Journal: British Journal of Dermatology (1992)

Journal Article A novel tissue preservation medium for immunoperoxidase staining of skin biopsies Get access A. CARMICHAEL, A. CARMICHAEL Departments of Pathology Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar G.R. COGHILL, G.R. COGHILL Departments of Pathology Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar I.A. CREE, I.A. CREE Departments of Pathology Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Dr I. A. Cree, Department of Pathology, University of Dundee, Ninewells Hospital and Medical School, Dundee DDI 9SY, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. GEORGE, S. GEORGE Departments of Dermatology, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.G. LOWE J.G. LOWE Departments of Dermatology, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 6, 1 December 1992, Pages 580–584, https://doi.org/10.1111/j.1365-2133.1992.tb14869.x Published: 01 December 1992
Determinants of perception of heartburn and regurgitation
Authors: A J Bredenoord
Journal: Gut (2005)

It is not known why some reflux episodes evoke symptoms and others do not. We investigated the determinants of perception of gastro-oesophageal reflux.In 32 patients with symptoms suggestive of gastro-oesophageal reflux, 24 hour ambulatory pH and impedance monitoring was performed after cessation of acid suppressive therapy. In the 20 patients who had at least one symptomatic reflux episode, characteristics of symptomatic and asymptomatic reflux episodes were compared.A total of 1807 reflux episodes were detected, 203 of which were symptomatic. Compared with asymptomatic episodes, symptomatic episodes were associated with a larger pH drop (p<0.001), lower nadir pH (p<0.05), and higher proximal extent (p<0.005). Symptomatic reflux episodes had a longer volume and acid clearance time (p<0.05 and p<0.002). Symptomatic episodes were preceded by a higher oesophageal cumulative acid exposure time (p<0.05). The proximal extent of episodes preceding regurgitation was larger than those preceding heartburn; 14.8% of the symptomatic reflux episodes were weakly acidic. In total, 426 pure gas reflux episodes occurred, of which 12 were symptomatic. Symptomatic pure gas reflux was more frequently accompanied by a pH drop than asymptomatic gas reflux (p<0.05).Heartburn and regurgitation are more likely to be evoked when the pH drop is large, proximal extent of the refluxate is high, and volume and acid clearance is delayed. Sensitisation of the oesophagus occurs by preceding acid exposure. Weakly acidic reflux is responsible for only a minority of symptoms in patients off therapy. Pure gas reflux associated with a pH drop ("acid vapour") can be perceived as heartburn and regurgitation.
Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism
Authors: Fang Yan, Hanwei Cao, Timothy L. Cover, M. Kay Washington, Yan Shi, LinShu Liu, Rupesh Chaturvedi, Richard M. Peek, Keith T. Wilson, D. Brent Polk
Journal: Journal of Clinical Investigation (2011)

Probiotic bacteria can potentially have beneficial effects on the clinical course of several intestinal disorders, but our understanding of probiotic action is limited. We have identified a probiotic bacteria-derived soluble protein, p40, from Lactobacillus rhamnosus GG (LGG), which prevents cytokine-induced apoptosis in intestinal epithelial cells. In the current study, we analyzed the mechanisms by which p40 regulates cellular responses in intestinal epithelial cells and p40's effects on experimental colitis using mouse models. We show that the recombinant p40 protein activated EGFR, leading to Akt activation. Activation of EGFR by p40 was required for inhibition of cytokine-induced apoptosis in intestinal epithelial cells in vitro and ex vivo. Furthermore, we developed a pectin/zein hydrogel bead system to specifically deliver p40 to the mouse colon, which activated EGFR in colon epithelial cells. Administration of p40-containing beads reduced intestinal epithelial apoptosis and disruption of barrier function in the colon epithelium in an EGFR-dependent manner, thereby preventing and treating DSS-induced intestinal injury and acute colitis. Furthermore, p40 activation of EGFR was required for ameliorating colon epithelial cell apoptosis and chronic inflammation in oxazolone-induced colitis. These data define what we believe to be a previously unrecognized mechanism of probiotic-derived soluble proteins in protecting the intestine from injury and inflammation.
Responses of the Sino-atrial Node to Change in Pressure in the Sinus Node Artery
Authors: KOROKU HASHIMOTO, SHIGEO TANAKA, MINORU HIRATA, SHIGEOTOSHI CHIBA
Journal: Circulation Research (1967)

The sino-atrial node area was perfused selectively through the right atrial artery in 76 dogs. The relationship between changes in the blood pressure in this artery and sinus node rhythmicity was studied in 56 hearts in which the major blood supply to the sinus node artery came from the right atrial artery. A reciprocal relation was observed between changes of blood pressure in the sinus node artery and the sinus rate. Some characteristics were: (1) The negative chronotropic effect induced by raising the blood pressure was linearly related to the Degrees of pressure change and more prominent than the positive chronotropic effect induced by reducing the pressure. (2) This relationship was most prominent in a limited range between 20 and 100 mm Hg. (3) Dichloroisoproterenol, atropine, hexamethonium, reserpine and vagotomy did not modify these responses. It is concluded that this localized mechanosensitivity of the sinus node to changes in arterial pressure may be responsible for the regulation of the heart rate in the lower range of blood pressure and that complete regulation of the heart rate is achieved physiologically in combination with the reflexes through the carotid and aortic nerves.