tbuckley/cabot-search huggingface dataset:
Hepatic Inactivation of Renin
Authors: ROBERT HEACOX, ALICE M. HARVEY, ARTHUR J. VANDER
Journal: Circulation Research (1967)

Renin activities were measured in plasma from an artery and from the hepatic, portal, and renal veins of anesthetized dogs. A significant arterial-hepatic venous renin difference was observed during control periods and after elevation of arterial renin by stimulation of endogenous renin secretion (induced by acute salt depletion) or by infusion of exogenous renin. There was good quantitative agreement between the calculated rates of renin infusion and hepatic renin clearance. No significant arterial-portal venous renin difference was observed. Infusion of exogenous renin decreased the usual renal venous-arterial renin difference; slight net renal inactivation of renin was observed in only 2 of 12 periods. We conclude that the liver is the major site of renin inactivation.
Suppression of proHB-EGF Carboxy-Terminal Fragment Nuclear Translocation: A New Molecular Target Therapy for Gastric Cancer
Authors: Takaya Shimura, Hiromi Kataoka, Naotaka Ogasawara, Eiji Kubota, Makoto Sasaki, Satoshi Tanida, Takashi Joh
Journal: Clinical Cancer Research (2008)

Inactivation of epidermal growth factor (EGF) receptor (EGFR) represents a promising strategy for the development of selective therapies against epithelial cancers and has been extensively studied as a molecular target for cancer therapy. However, little attention has been paid to remnant cell-associated domains created by cleavage of EGFR ligands. The present study focused on recent findings that cleavage of membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF), an EGFR ligand, induces translocation of the carboxyl-terminal fragment (CTF) of HB-EGF from the plasma membrane to the nucleus and regulates cell cycle.Two gastric cancer cell lines, MKN28 and NUGC4, were used. KB-R7785, an inhibitor of proHB-EGF shedding, was used to suppress HB-EGF-CTF nuclear translocation with cetuximab, which inhibits EGFR phosphorylation. Cell growth was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay, apoptosis was evaluated by assay of caspase-3 and caspase-7, and cell cycle was investigated by flow cytometry.Immunofluorescence study confirmed that KB-R7785 inhibited HB-EGF-CTF nuclear translocation under conditions of proHB-EGF shedding induction by 12-O-tetradecanoylphorbol-13-acetate in gastric cancer cells. KB-R7785 inhibited cell growth in a dose-dependent manner and high-dose KB-R7785 induced apoptosis. Moreover, KB-R7785 induced cell cycle arrest and increased sub-G1 DNA content. KB-R7785 suppressed cyclin A and c-Myc expression. All effects of KB-R7785 were reinforced by combination with cetuximab.These results suggest that both inhibition of EGFR phosphorylation and inhibition of HB-EGF-CTF nuclear translocation play crucial roles in inhibitory regulation of cancer cell growth. Suppression of HB-EGF-CTF nuclear translocation might offer a new strategy for treating gastric cancer.
Observations on DIURETICS AND THEIR USES
Authors: D. M. Lyon
Journal: BMJ (1933)

organism, and some are more jealously guarded than Observations others.Among the most important are the blood volume ON and the physical and chemical composition of the blood.DIURETICS AND THEIR USES * l When the composition of the plasma changes an endeavour DIURETICS ANDTHEIR USES *is made to keep the osmotic pressure constant.The BY regulation of the water economy centres in the blood, D.
Adaptive Evolution of Genes Duplicated from the Drosophila pseudoobscura neo-X Chromosome
Authors: R. P. Meisel, B. B. Hilldorfer, J. L. Koch, S. Lockton, S. W. Schaeffer
Journal: Molecular Biology and Evolution (2010)

Drosophila X chromosomes are disproportionate sources of duplicated genes, and these duplications are usually the result of retrotransposition of X-linked genes to the autosomes.The excess duplication is thought to be driven by natural selection for two reasons: X chromosomes are inactivated during spermatogenesis, and the derived copies of retroposed duplications tend to be testis expressed.Therefore, autosomal derived copies of retroposed genes provide a mechanism for their X-linked paralogs to ''escape'' X inactivation.Once these duplications have fixed, they may then be selected for male-specific functions.Throughout the evolution of the Drosophila genus, autosomes have fused with X chromosomes along multiple lineages giving rise to neo-X chromosomes.There has also been excess duplication from the two independent neo-X chromosomes that have been examined-one that occurred prior to the common ancestor of the willistoni species group and another that occurred along the lineage leading to Drosophila pseudoobscura.To determine what role natural selection plays in the evolution of genes duplicated from the D. pseudoobscura neo-X chromosome, we analyzed DNA sequence divergence between paralogs, polymorphism within each copy, and the expression profiles of these duplicated genes.We found that the derived copies of all duplicated genes have elevated nonsynonymous polymorphism, suggesting that they are under relaxed selective constraints.The derived copies also tend to have testis-or male-biased expression profiles regardless of their chromosome of origin.Genes duplicated from the neo-X chromosome appear to be under less constraints than those duplicated from other chromosome arms.We also find more evidence for historical adaptive evolution in genes duplicated from the neo-X chromosome, suggesting that they are under a unique selection regime in which elevated nonsynonymous polymorphism provides a large reservoir of functional variants, some of which are fixed by natural selection.
Gender Differences in Posttraumatic Stress Disorder After Motor Vehicle Accidents
Authors: Carol S. Fullerton, Robert J. Ursano, Richard S. Epstein, Brian Crowley, Kelley Vance, Tzu-Cheg Kao, Angela Dougall, Andrew Baum
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Women have higher rates of posttraumatic stress disorder (PTSD) than men. The authors examined prior trauma, PTSD, major depression, anxiety disorder not including PTSD, and peritraumatic dissociation; current peritraumatic dissociation; and passenger injury as possible explanations for the different rates of acute PTSD in women and men after a serious motor vehicle accident. METHOD: Subjects age 18–65 years who had been in a serious motor vehicle accident (N=122) were assessed with the Structured Clinical Interview for DSM-III-R and the Peritraumatic Dissociative Experiences Questionnaire—Rater Version 1 month after the accident. RESULTS: Women did not differ from men in meeting the overall reexperiencing criterion for a diagnosis of PTSD (criterion B), but women were at greater risk for the specific reexperiencing symptoms of intense feelings of distress in situations similar to the motor vehicle accident and physical reactivity to memories of the motor vehicle accident. Women were 4.7 times more likely than men to meet the overall avoidance/numbing criterion (criterion C) and 3.8 times more likely to meet the overall arousal criterion (criterion D). Women were more likely than men to report the criterion C symptoms of avoiding thoughts and situations associated with the accident, loss of interest in significant activities, and a sense of foreshortened future and the criterion D symptoms of trouble sleeping, difficulty concentrating, and exaggerated startle response. Multiple logistic regression analysis indicated that the gender differences in acute PTSD were not associated with prior trauma, PTSD, peritraumatic dissociation, major depression, or anxiety disorder not including PTSD or with passenger injury. However, peritraumatic dissociative symptoms at the time of the accident were associated with a significantly higher risk for acute PTSD in women than in men. CONCLUSIONS: Gender differences in peritraumatic dissociation may help explain differences in risk for PTSD and for some PTSD symptoms in women and men.
Effect of oxidative stress on respiratory epithelium from children with Down syndrome
Authors: Martijn Bruijn, René Lutter, Eric Eldering, Albert P. Bos, Job B.M. van Woensel
Journal: European Respiratory Journal (2012)

Children with Down syndrome are at high risk for acute respiratory distress syndrome. In Down syndrome, both regulation of inflammation and apoptosis, important in acute respiratory distress syndrome pathophysiology, are abnormal. This has been linked to an imbalance in free radical scavengers. We investigated the expression of free radical scavengers and the effect of oxidative stress in terms of apoptosis and inflammation in respiratory epithelium from children with Down syndrome compared with control subjects. We cultured primary nasal epithelial cells from Down syndrome children (n=12) and controls (n=17) and exposed them to oxidative stress by supplementing superoxide. First we showed that the expression of the free radical scavengers CuZn-superoxide dismutase was 28% higher (p=0.06), catalase was 36% lower (p=0.04) and glutathione peroxidase was 73% lower (p=0.004) in Down syndrome children compared with controls. We found no significant difference in apoptosis, between Down syndrome and control subjects after exposure to oxidative stress. We also found no significant difference in levels of interleukin (IL)-1β, IL-6, IL-8, vascular endothelial growth factor and granulocyte colony-stimulating factor in primary nasal epithelial cell supernatant after exposure to oxidative stress between Down syndrome and control subjects. We found an imbalance in free radical scavengers in respiratory epithelial cells from children with Down syndrome, but this did not result in increased levels of either apoptosis or inflammation upon exposure to oxidative stress.
Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk
Authors: Dalemari Crowther-Swanepoel, Peter Broderick, Maria Chiara Di Bernardo, Sara E Dobbins, María Torres, Mahmoud Mansouri, Clara Ruiz-Ponte, Anna Enjuanes, Richard Rosenquist, Angel Carracedo, Jesper Jurlander, Elias Campo, Gunnar Juliusson, Emilio Montserrat, Karin E Smedby, Martin J S Dyer, Estella Matutes, Claire Dearden, Nicola J Sunter, Andrew G Hall, Tryfonia Mainou-Fowler, Graham H Jackson, Geoffrey Summerfield, Robert J Harris, Andrew R Pettitt, David J Allsup, James R Bailey, Guy Pratt, Chris Pepper, Chris Fegan, Anton Parker, David Oscier, James M Allan, Daniel Catovsky, Richard S Houlston
Journal: Nature Genetics (2010)
CLINICAL STUDIES ON a-(2-PIPERIDYL) BENZHYDROL HYDROCHLORIDE, A NEW ANTIDEPRESSANT DRUG
Authors: HOWARD D. FABING, J. ROBERT HAWKINS, JAMES A. L. MOULTON
Journal: American Journal of Psychiatry (1955)

1. The pharmacology of a new antidepressant drug, Meratran, is reviewed briefly. 2. Clinical trial in 320 cases disclosed that the therapeutic indications of this compound are roughly similar to those of the amphetamines. 3. Reactive depressions responded effectively in 90% of our relatively small series. 4. Endogenous depressions responded favorably in 65% of our cases. 5. The drug has proved valuable in office practice because the appetite loss and the cardiovascular pressor reactions sometimes observed after the administration of the amphetamines are not encountered. In addition the drug seldom interferes with nocturnal sleep, and when it produces anxiety side reactions these are less severe and less disturbing subjectively than those encountered with the amphetamines. 6. When anxiety or agitation comprise a sizable proportion of the clinical picture the drug should be used with caution. 7. Preliminary observations indicate that the drug may have therapeutic usefulness, in addition to the depressive states, in some of the tics, in narcolepsy, and as an adjunct in the management of certain epileptics. 8. Effective dosage ranges (except in narcolepsy) vary between 3.0 and 25.0 mg. daily. 9. Wider clinical trial of this compound appears justified.
Regulation of TCR δ and α repertoires by local and long-distance control of variable gene segment chromatin structure
Authors: Abbas Hawwari, Michael S. Krangel
Journal: The Journal of Experimental Medicine (2005)

Murine Tcrd and Tcra gene segments reside in a single genetic locus and undergo recombination in CD4−CD8− (double negative [DN]) and CD4+CD8+ (double positive [DP]) thymocytes, respectively. TcraTcrd locus variable gene segments are subject to complex regulation. Only a small subset of ∼100 variable gene segments contributes substantially to the adult TCRδ repertoire. Moreover, although most contribute to the TCRα repertoire, variable gene segments that are Jα proximal are preferentially used during primary Tcra recombination. We investigate the role of local chromatin accessibility in determining the developmental pattern of TcraTcrd locus variable gene segment recombination. We find variable gene segments to be heterogeneous with respect to acetylation of histones H3 and H4. Those that dominate the adult TCRδ repertoire are hyperacetylated in DN thymocytes, independent of their position in the locus. Moreover, proximal variable gene segments show dramatic increases in histone acetylation and germline transcription in DP thymocytes, a result of super long-distance regulation by the Tcra enhancer. Our results imply that differences in chromatin accessibility contribute to biases in TcraTcrd locus variable gene segment recombination in DN and DP thymocytes and extend the distance over which the Tcra enhancer can regulate chromatin structure to a remarkable 525 kb.
Tissue Inhibitor of Metalloproteinases-4. The road less traveled
Authors: Jorge Melendez-Zajgla, Luis Pozo, Gisela Ceballos, Vilma Maldonado
Journal: Molecular Cancer (2008)

Tissue inhibitors of metalloproteinases (TIMPs) regulate diverse processes, including extracellular matrix (ECM) remodeling, and growth factors and their receptors' activities through the inhibition of matrix metalloproteinases (MMPs). Recent evidence has shown that this family of four members (TIMP-1 to TIMP-4) can also control other important processes, such as proliferation and apoptosis, by a mechanism independent of their MMP inhibitory actions. Of these inhibitors, the most recently identified and least studied is TIMP-4. Initially cloned in human and, later, in mouse, TIMP-4 expression is restricted to heart, kidney, pancreas, colon, testes, brain and adipose tissue. This restricted expression suggests specific and different physiological functions. The present review summarizes the information available for this protein and also provides a putative structural model in order to propose potential relevant directions toward solving its function and role in diseases such as cancer.
Thymus-Derived Lymphocytes in Patients With Bilharzial Urinary Bladder Cancer: Brief Communication
Authors: Adel M. A. El-Asfahani, Faiza Hammouda, Hassan N. Tawfik, Mahmoud Sherif, Amal S. Ibrahim, Gene I. Higashi, Mahmoud Daw, Mohamed Safwat, Rolf F. Barth
Journal: JNCI Journal of the National Cancer Institute (1977)

The purpose of the present study was to determine the levels of peripheral blood thymus-derived (T) lymphocytes in a series of 43 Egyptian patients with bilharzial bladder cancer and 15 with chronic bilharziasis and to compare these to normal Egyptian controls. Both active and total T-cell rosettes were significantly reduced in patients with stages III and IV bladder cancer, whereas only total T-cell rosettes were reduced in patients with stages I and II disease when compared to normal controls. Patients with chronic bilharziasis had intermediate values between those with cancer and normal controls, but this difference was significant only for total T-cell rosettes. Only those patients with advanced disease (stages III and IV) had significantly lower percentages of active T-lymphocytes when compared to patients with bilharziasis. Since total T-cell levels were reduced significantly in cancer patients with both early (stages I and II) and advanced (stages III and IV) disease when compared to normal controls and patients with bilharziasis, only the number of active T-cells could be correlated with the clinical stage of disease.
Reliability of ratings of perceived exertion during progressive treadmill exercise.
Authors: K L Lamb, R G Eston, D Corns
Journal: British Journal of Sports Medicine (1999)

To assess the test-retest reliability (repeatability) of Borg's 6-20 rating of perceived exertion (RPE) scale using a more appropriate statistical technique than has been employed in previous investigations. The RPE scale is used widely in exercise science and sports medicine to monitor and/or prescribe levels of exercise intensity. The "95% limits of agreement" technique has recently been advocated as a better means of assessing within-subject (trial to trial) agreement than traditional indicators such as Pearson and intraclass correlation coefficients.Sixteen male athletes (mean (SD) age 23.6 (5.1) years) completed two identical multistage (incremental) treadmill running protocols over a period of two to five days. RPEs were requested and recorded during the final 15 seconds of each three minute stage. All subjects successfully completed at least four stages in each trial, allowing the reliability of RPE responses to be examined at each stage.The 95% limits of agreement (bias +/- 1.96 x SDdiff) were found to widen as exercise intensity increased: 0.88 (2.02) RPE units (stage 1), 0.25 (2.53) RPE units (stage 2), -0.13 (2.86) RPE units (stage 3), and -0.13 (2.94) RPE units (stage 4). Pearson correlations (0.81, 0.72, 0.65, and 0.60) and intraclass correlations (0.82, 0.80, 0.77, and 0.75) decreased as exercise intensity increased.These findings question the test-retest reliability of the RPE scale when used to monitor subjective estimates of exercise intensity in progressive (or graded) exercise tests.
The interpersonal foundations of thinking
Authors: R. Peter Hobson
Journal: Behavioral and Brain Sciences (2005)

Tomasello et al. provide a convincing account of the origins of cultural cognition. I highlight how emotionally grounded sharing of experiences (not merely or predominantly intentions) is critical for the development of interpersonal understanding and perspective-sensitive thinking. Such sharing is specifically human in quality as well as motivation, and entails forms of self–other connectedness and differentiation that are essential to communication and symbolic functioning.
Effect of Blood Pressure Lowering and Antihypertensive Drug Class on Progression of Hypertensive Kidney Disease&lt;SUBTITLE&gt;Results From the AASK Trial&lt;/SUBTITLE&gt;
Authors: Jackson T. Wright, Jr
Journal: JAMA (2002)

ContextHypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD.ObjectiveTo compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension.DesignRandomized 3 × 2 factorial trial with enrollment from February 1995 to September 1998.Setting and ParticipantsA total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m2) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years.InterventionsParticipants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a β-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals.Main Outcome MeasuresRate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or ≥25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol.ResultsAchieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (−2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (−1.95 [0.17] mL/min per 1.73 m2 per year; P = .24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], −22% to 21%; P = .85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P = .04) and 38% (95% CI, 14%-56%; P = .004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups.ConclusionsNo additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than β-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.
MEASUREMENT OF SENSORY CHRONAXIE AS A DIAGNOSTIC PROCEDURE IN SCLERODERMA
Authors: Stefania Jablonska
Journal: British Journal of Dermatology (1975)

Journal Article MEASUREMENT OF SENSORY CHRONAXIE AS A DIAGNOSTIC PROCEDURE IN SCLERODERMA Get access Stefania Jablonska Stefania Jablonska Department of Dermatology, Warsaw School of Medicine, 02–008 Warsaw, 82A Koszykowa ST Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 92, Issue 2, 1 February 1975, Pages 223–226, https://doi.org/10.1111/j.1365-2133.1975.tb03064.x Published: 01 February 1975
Hypoxia and Hypercapnia From Bedcovers
Authors: Allen B. King
Journal: JAMA (1972)

<h3>To the Editor.—</h3> This letter calls attention to the effects of pulling bedcoverings over the head upon retiring, thus creating a mild but potentially dangerous hypoxic and hypercapnic environment. <h3>Methods.—</h3> The effect on the inspired oxygen and carbon dioxide concentrations was studied in five healthy men, 25 to 30 years old. Each volunteer rested quietly though not sleeping, in the left lateral decubitus position on a sheet-covered mattress. The head was covered for ten minutes by one sheet and one standard AUS blanket weighing 3 to 4 lb and then by one sheet and<i>two</i>blankets for an additional ten minutes. All coverings were tucked under the mattress except the headward edge which was laid flat on the top surface. Samples of air from under the covers were obtained at one, five, and ten minutes from a catheter placed adjacent to the mouth of the subject. The subject held his