tbuckley/cabot-search huggingface dataset:
Short course acid suppressive treatment for patients with functional dyspepsia: results depend on Helicobacter pylori status
Authors: A L Blum
Journal: Gut (2000)

<h3>BACKGROUND AND AIMS</h3> Treatment of functional dyspepsia with acid inhibitors is controversial and it is not known if the presence of<i>Helicobacter pylori</i> infection influences the response. <h3>METHODS</h3> After a complete diagnostic workup, 792 patients with functional dyspepsia unresponsive to one week of low dose antacid treatment were randomised to two weeks of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, or omeprazole 20 mg daily. Individual dyspeptic and other abdominal symptoms were evaluated before and after treatment according to <i>H pylori</i> status. <h3>RESULTS</h3> The proportions of patients considered to be in remission (intention to treat) at the end of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, and omeprazole 20 mg were, respectively, 42%, 50%, 48%, and 59% in the <i>H pylori</i> positive group and 66%, 73%, 64%, and 71% in the <i>H pylori </i>negative group. In <i>H pylori</i>positive patients, the therapeutic gain over placebo was significant for omeprazole 20 mg (17.6%, 95% confidence intervals (CI) 4.2–31.0; p&lt;0.014 using the Bonferroni-adjusted p level of 0.017) but not for omeprazole 10 mg (6.8%, 95% CI −6.7–20.4) or ranitidine 150 mg (8.9%, 95% CI −4.2–21.9). There was no significant therapeutic gain from active treatment over placebo in <i>H pylori</i> negative patients. Complete disappearance of symptoms and improvement in quality of life also occurred most frequently with omeprazole 20 mg and was significant in both <i>H pylori</i> positive and <i>H pylori</i> negative groups. The six month relapse rate of symptoms requiring treatment was low (&lt;20%) in all groups. <h3>CONCLUSIONS</h3> Omeprazole 20 mg per day had a small but significant favourable effect on outcome in <i>H pylori</i> positive patients. The differential response in these patients may be explained by an enhanced antisecretory response in the presence of <i>H pylori.</i> The effect of weaker acid inhibition was unsatisfactory.
Conference on the Role of the Renal Pressor System in Maintenance of Experimental Renal Hypertension
Authors: HARRY GOLDBLATT
Journal: Circulation (1958)

The hypothetical presence of increased circulating renin or hypertensin in chronic renal hypertension was debated; eventually it was agreed that methods were too insensitive for accurate assay. Pressor amounts of infused renin could not be detected by some methods of bioassay (Dr. Wakerlin). Hypertensinase activity in blood may destroy the end product before the assay can be performed (Dr. Blaquier). Perhaps rapid tissue removal from circulating blood may account for the inadequacy of the results (Dr. Skeggs). Previous experiments to detect these substances in circulating hypertensive blood have been indecisive (Dr. Braun-Menéndez) or only weakly positive (Drs. Goldblatt and Skeggs) and the clear-cut depressor effects of antirenin might act on a hypothetical nonpressor action of renin (Dr. Wakerlin). Dr. Helmer commented on the sustained pressor substance found in renal vein blood of hypertensive rats. Dr. Grollman believed chronic renal hypertension to be due to interference with an essential function of the kidney which in the normal animal prevents the blood pressure from rising. The failure of the blood pressure to rise when the kidneys from renal hypertensive dogs were perfused in situ by normotensive recipients was again discussed by Drs. Surtshin, Goldblatt and Grollman, and the possible fallacies involved in reasoning from such acute experiments were brought out. The nature of the stimulus to renin release was discussed again by Dr. Kolff. Non pulsatile flow was probably not a requirement (Dr. Kolff), nor was renal ischemia (Dr. Wakerlin), but some alteration in renal function seemed to be necessary (Dr. Goldblatt). Dr. Wakerlin and Dr. Rodbard advocated, respectively, the view that the primary stimulus might be the volume pulse or the transmural pressure in the renal arterial bed. An objection to renin as the cause of chronic hypertension based on tachyphylaxis experiments was raised by Dr. Findley. Dr. Goldblatt denied the presence of true tachyphylaxis and was supported by Drs. Helmer and Wakerlin. Dr. McCubbin suggested it might occur only with cruder preparations of renin, and Dr. Braun-Menéndez theorized that receptor sites might be occupied for a time after restoration of normal blood pressure, thus giving rise to a transient tachyphylaxis. Dr. Bumpus supported this explanation by reporting that a pressor response to crude angiotonin can sometimes not be maintained, while the response to pure angiotonin is persistent. Considerable discussion ensued between Drs. Goldblatt and Grollman concerning the mechanism of blood pressure reduction by removal of a single ischemic kidney. The human renal biopsy and autopsy studies suggesting the primacy of renal arteriolosclerosis in human hypertension were reviewed by Dr. Goldblatt.
Lost in Transition: Challenges and Opportunities for Improving the Quality of Transitional Care
Authors: Eric A. Coleman, Robert A. Berenson
Journal: Annals of Internal Medicine (2004)

Transitional care has been defined as a set of actions designed to ensure the coordination and continuity of health care as patients transfer between different locations or different levels of care in the same location. Transitional care, which primarily concerns the relatively brief time interval that begins with preparing a patient to leave one setting and concludes when the patient is received in the next setting, poses challenges that distinguish it from other types of care. Many transitions are unplanned, result from unanticipated medical problems, occur in “real time” during nights and on weekends, involve clinicians who may not have an ongoing relationship with the patient, and happen so quickly that formal and informal support mechanisms cannot respond in a timely manner. This article describes the challenges involved in and potential solutions for improving the quality of transitional care.
The hepatotoxic metabolite of acetaminophen directly activates the Keap1-Nrf2 cell defense system
Authors: Ian M. Copple, Christopher E. Goldring, Rosalind E. Jenkins, Alvin J. L. Chia, Laura E. Randle, John D. Hayes, Neil R. Kitteringham, B. Kevin Park
Journal: Hepatology (2008)

The transcription factor Nrf2 regulates the expression of numerous cytoprotective genes in mammalian cells. We have demonstrated previously that acetaminophen activates Nrf2 in mouse liver following administration of non-hepatotoxic and hepatotoxic doses in vivo, implying that Nrf2 may have an important role in the protection against drug-induced liver injury. Nrf2 activation has been proposed to occur through the modification of cysteine residues within Keap1, the cytosolic repressor of Nrf2. We hypothesized that acetaminophen activates Nrf2 via the formation of its reactive metabolite N-acetyl-p-benzoquinoneimine (NAPQI), which may disrupt the repression of Nrf2 through the modification of cysteine residues within Keap1. Here, we show that NAPQI can directly activate the Nrf2 pathway in mouse liver cells, inducing an adaptive defense response that is antagonized by RNA interference targeted against Nrf2. Furthermore, mass spectrometric analysis shows that NAPQI selectively modifies cysteine residues in Keap1, both in recombinant protein in vitro and in cells ectopically expressing Keap1. Using this cell-based model, we demonstrate that activation of Nrf2 by NAPQI and a panel of probe molecules [dexamethasone 21-mesylate, 15-deoxy-Δ-(12,14)-prostaglandin J2, 2,4-dinitrochlorobenzene, and iodoacetamide] correlates with the selective modification of cysteine residues located within the intervening region of Keap1. However, substantial depletion of glutathione (to less than 15 % of basal levels) by buthionine sulfoximine, which does not directly modify Keap1, is also sufficient to activate Nrf2. Conclusion: Nrf2 can be activated via the direct modification of cysteine residues located within the intervening region of Keap1, but also via the substantial depletion of glutathione without the requirement for direct modification of Keap1. It is possible that both of these mechanisms contribute to the activation of Nrf2 by acetaminophen. (HEPATOLOGY 2008.)
Incorporation of &lt;sup&gt;32&lt;/sup&gt;P Into Nucleic Acids in Mammary Tissue of Mice Susceptible and Resistant to Breast Cancer
Authors: Nandini A. Sheth, Sumati V. Bhide, Kamal J. Ranadive
Journal: JNCI Journal of the National Cancer Institute (1971)

Incorporation of 32P into RNA and DNA fractions of mammary and tumor tissue was studied in virgin C3H mice, which are susceptible to the development of breast cancer. Virgin C57BL mice, which are resistant to the development of breast cancer, were the controls. Virgin C3H and C57BL mice, 4 and 8 months old, and tumor-bearing C3H mice were used as the experimental groups. The incorporation of 32P into RNA and DNA fractions did not differ significantly among the 4- and 8-month-old, virgin C3H mice. The tumor tissue had the highest rate of uptake of 32P into both nucleic acids. In castrated C3H mice and C57BL females, the incorporation of 32P into nucleic acids in the mammary tissue of the C57BL females was significantly lowered, whereas in the C3H mice it remained comparable with that observed in the corresponding control groups.
The role of the novel Th17 cytokine IL-26 in intestinal inflammation
Authors: J Dambacher, F Beigel, K Zitzmann, E N De Toni, B Goke, H M Diepolder, C J Auernhammer, S Brand
Journal: Gut (2008)

<h3>Background and aims:</h3> Interleukin 26 (IL-26), a novel IL-10-like cytokine without a murine homologue, is expressed in T helper 1 (Th1) and Th17 cells. Currently, its function in human disease is completely unknown. The aim of this study was to analyse its role in intestinal inflammation. <h3>Methods:</h3> Expression studies were performed by reverse transcription-PCR (RT-PCR), quantitative PCR, western blot and immunohistochemistry. Signal transduction was analysed by western blot experiments and ELISA. Cell proliferation was measured by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. IL-26 serum levels were determined by an immunoluminometric assay (ILMA). <h3>Results:</h3> All examined intestinal epithelial cell (IEC) lines express both IL-26 receptor subunits IL-20R1 and IL-10R2. IL-26 activates extracellular signal-related kinase (ERK)-1/2 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) mitogen-activated protein (MAP) kinases, Akt and signal transducers and activators of transcription (STAT) 1/3. IL-26 stimulation increases the mRNA expression of proinflammatory cytokines but decreases cell proliferation. In inflamed colonic lesions of patients with Crohn’s disease, an elevated IL-26 mRNA expression was found that correlated highly with the IL-8 and IL-22 expression. Immunohistochemical analysis demonstrated IL-26 protein expression in colonic T cells including Th17 cells expressing the orphan nuclear receptor RORγt, with an increased number of colonic IL-26-expressing cells in active Crohn’s disease. <h3>Conclusion:</h3> Intestinal cells express the functional IL-26 receptor complex. IL-26 modulates IEC proliferation and proinflammatory gene expression and its expression is upregulated in active Crohn’s disease, indicating a role for this cytokine system in the innate host cell response during intestinal inflammation. For the first time, IL-26 expression is demonstrated in colonic RORγt-expressing Th17 cells in situ, supporting a role for this cell type in the pathogenesis of Crohn’s disease.
Relation between iron stores and non-insulin dependent diabetes in men: case-control study
Authors: J. T Salonen, T.-P. Tuomainen, K. Nyyssonen, H.-M. Lakka, K. Punnonen
Journal: BMJ (1998)

Non-insulin dependent diabetes mellitus is a common complication of diseases of iron overload such as haemochromatosis; 53-80% of patients with haemochromatosis develop diabetes.1 The development of diabetes in haemochromatosis is related to the magnitude of the excess iron.1 In a cross sectional, population based study of over 1000 middle aged men in eastern Finland we found that fasting concentrations of serum insulin and blood glucose were raised in men with high serum concentrations of ferritin (an indication of raised stores of iron).2 Iron is a catalyst of free radical stress, and it has been suggested that free radicals and lipid peroxidation play a part in the aetiology of diabetes.3 Formation of hydroxyl radicals catalysed by iron may play an important part in the development of diabetes since the cells that produce insulin are extraordinarily sensitive to damage from oxidation.3 In another cohort study low plasma concentrations of …
Synthesizing life history theory with sexual selection: Toward a comprehensive model of alternative reproductive strategies
Authors: Jenée James Jackson, Bruce J. Ellis
Journal: Behavioral and Brain Sciences (2009)

Abstract Del Giudice's model of sex-specific attachment patterns demonstrates the usefulness of infusing life history theory with principles of sexual selection. We believe a full synthesis between the two theories provides a foundation for a comprehensive model of alternative reproductive strategies. We extend Del Giudice's ideas based on our own program of research, focusing specifically on the importance of intrasexual competition and the individual phenotype during development.
A novel neurogenic vasodilator mechanism in bovine mesenteric artery.
Authors: K L Axelsson, M E Ljusegren, J Ahlner, N Grundström
Journal: Circulation Research (1989)

The presence of a neurogenic vasodilator mechanism was investigated in isolated bovine mesenteric arteries (BMAs) that were precontracted with phenylephrine. Electrical field stimulation induced tetrodotoxin-sensitive relaxations in guanethidine-pretreated BMAs. The relaxation occurred after a delay of about 5-8 seconds and amounted to 25-35% in different sets of experiments. The relaxation was not affected by classical receptor antagonists such as atropine (1 microM), cimetidine (3.9 microM), clemastine (2.8 microM), naloxone (1.2 microM), 8-phenyltheophylline (1 microM), propranolol (3.4 microM), ritanserin (5 microM), or droperidol (13 microM). The nicotinic acetylcholine-receptor stimulant 1,1-dimethyl-4-phenyl-piperazinium iodide (10 microM) was without effect on the relaxation, and removal of the endothelium of the arteries also had no effect. The bee venom component apamin (1 microM), which has been shown to block the nonadrenergic, noncholinergic relaxation in intestinal and vascular smooth muscle from other species, was also found to be without effect on the relaxation induced by electrical field stimulation in BMAs. Pretreatment of the arteries with capsaicin (1 microM) had no effect per se and did not affect the relaxation induced by a subsequent stimulation. Capsaicin has been suggested to release neurotransmitter and eventually deplete neurons containing substance P and calcitonin gene-related peptide. Furthermore, exogenously applied calcitonin gene-related peptide (1-100 nM), substance P (10 nM-1 microM), and vasoactive intestinal peptide (0.3-30 nM) gave relaxations amounting to less than 10%. It is postulated that electrical field stimulation induces a neurogenic relaxation of a nonadrenergic, noncholinergic nature in BMAs.(ABSTRACT TRUNCATED AT 250 WORDS)
Disruption of the lung structure maintenance programme: a comprehensive view of emphysema development
Authors: J.A. Barberà, V.I. Peinado
Journal: European Respiratory Journal (2011)

The lung is highly exposed to the external environment and must cope with a number of challenges from inhaled particles, toxic gases and invading microorganisms. Defence against these external injuries depends on various mechanisms (antioxidants, antiproteases and the immune response), and an efficient system for removing and replacing apoptotic cells. Failure to cope with external injury may lead to lung damage and destruction.

Emphysema is a characteristic feature in the lungs of patients with chronic obstructive pulmonary disease (COPD). Its pathogenesis is far from being completely understood. More than 40 yrs ago, investigators reported that the instillation of proteolytic enzymes in rats caused airspace enlargement 1 and that genetic deficiency in the neutrophil elastase inhibitor α1-antitripsin was also associated with emphysema 2. These observations led to the hypothesis that emphysema was the result of an imbalance between proteolytic and antiproteolytic agents. The subsequent demonstration of increased numbers of neutrophils and macrophages in the lungs of smokers, and the known capacity of these cells to produce proteolytic enzymes, pointed to a connection between the inflammatory reaction characteristic of COPD and proteolytic/antiproteolytic imbalance, leading to the prevalent theory of an inflammatory–proteolytic origin of lung destruction in COPD. This theory does not, however, explain all the features in the lung of patients with COPD 3. In recent years, alternative or complementary hypotheses have been proposed, including oxidative stress 4, apoptosis 5, cell senescence 6 and autoimmunity 7, providing a more complex and comprehensive view of the pathogenesis of emphysema in COPD.

Central to our current understanding of the pathogenesis of emphysema is the concept of a lung structure maintenance programme 8, 9, which considers that the lung is a metabolically active organ designed for gas exchange and the processing of endogenous substances constantly exposed …
Multicenter phase II study of trabectedin in patients with metastatic castration-resistant prostate cancer
Authors: M.D. Michaelson, J. Bellmunt, G.R. Hudes, S. Goel, R.J. Lee, P.W. Kantoff, C.A. Stein, P. Lardelli, I. Pardos, C. Kahatt, A. Nieto, M. Cullell-Young, N.L. Lewis, M.R. Smith
Journal: Annals of Oncology (2011)
Lamina-Specific Alterations in the Dopamine Innervation of the Prefrontal Cortex in Schizophrenic Subjects
Authors: M Akil, J N Pierri, R E Whitehead, C L Edgar, C Mohila, A R Sampson, D A Lewis
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: Abnormalities in dopamine neurotransmission in the prefrontal cortex have been implicated in the pathophysiology of schizophrenia. However, the integrity of the dopamine projections to the prefrontal cortex in this disorder has not been directly examined. METHOD: The authors employed immunocytochemical methods and antibodies against tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis, and the dopamine membrane transporter to examine dopamine axons in the dorsomedial prefrontal cortex (area 9) from 16 pairs of schizophrenic and matched control subjects. RESULTS: Compared to the control subjects, the total length of tyrosine hydroxylase-immunoreactive axons was unchanged in the superficial and middle layers of the schizophrenic subjects but was reduced by an average of 33.6% in layer 6. The total length of tyrosine hydroxylase-positive axons in layer 6 was decreased in 13 of the schizophrenic subjects compared to their control subjects. Axons immunoreactive for the dopamine membrane transporter showed a similar pattern of change. In contrast, axons labeled for the serotonin transporter did not differ between schizophrenic and control subjects in any layer examined. In addition, the density of tyrosine hydroxylase-containing axons did not differ between monkeys chronically treated with haloperidol and matched control animals. CONCLUSIONS: These findings reveal that schizophrenia is associated with an altered dopamine innervation of prefrontal cortex area 9 that is lamina- and neurotransmitter-specific and that does not appear to be a consequence of pharmacological treatment. Together, these data provide direct evidence for a disturbance in dopamine neurotransmission in the prefrontal cortex of schizophrenic subjects.
The punishment that sustains cooperation is often coordinated and costly
Authors: Samuel Bowles, Robert Boyd, Sarah Mathew, Peter J. Richerson
Journal: Behavioral and Brain Sciences (2012)

Abstract Experiments are not models of cooperation; instead, they demonstrate the presence of the ethical and other-regarding predispositions that often motivate cooperation and the punishment of free-riders. Experimental behavior predicts subjects' cooperation in the field. Ethnographic studies in small-scale societies without formal coercive institutions demonstrate that disciplining defectors is both essential to cooperation and often costly to the punisher.
Noninvasive ventilation or paradigm paralysis?
Authors: J.R. Bach, M.R. Gonçalves
Journal: European Respiratory Journal (2004)

<h3>ABSTRACT</h3> Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. MS prevalence varies geographically, both between and within countries and is notably high in Scotland. Disease trajectory varies significantly between individuals and the causes for this are largely unclear. Biomarkers predictive of disease course are urgently needed to allow improved stratification for current disease modifying therapies and future targeted treatments aimed at neuroprotection and remyelination, and as endpoints for clinical trials. Magnetic resonance imaging (MRI) can detect disease activity and underlying neurological damage non-invasively <i>in vivo</i> at the micro and macro structural level. FutureMS is a prospective Scottish longitudinal multi-centre cohort study which focuses on deeply phenotyping and genotyping patients with recently diagnosed relapsing-remitting MS (RRMS) to identify predictors of disease activity and severity. Neuroimaging is a central component of the study and provides two main primary endpoints for disease activity and neurodegeneration. The aim of the current paper is to provide an overview of MRI data acquisition, management and processing in FutureMS. MRI is acquired at baseline (N=431) and 1-year follow-up, in Dundee, Glasgow and Edinburgh (3T Siemens) and in Aberdeen (3T Philips), and managed and processed in Edinburgh. The core structural MRI protocol comprises T1-weighted, T2-weighted, 2D/3D FLAIR and proton density images. The original study primary imaging outcome measures are new/enlarging white matter lesions (WML) assessed by neuroradiological visual read and reduction in brain volume over one year. Secondary imaging outcomes comprise WML volume as an additional quantitative structural MRI outcome measure, rim lesions on susceptibility-weighted imaging (SWI), and microstructural MRI measures, including diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics, relaxometry, magnetisation transfer (MT) ratio, MT saturation and derived g-ratio measures. FutureMS aims to reduce uncertainty around disease course and allow for targeted treatment in RRMS by exploring the role of conventional and advanced MRI measures as biomarkers of disease severity and progression in a large population of RRMS patients in Scotland.
E-Z Reader's assumptions about lexical processing: Not so easy to define the two stages of word identification?
Authors: Sally Andrews
Journal: Behavioral and Brain Sciences (2003)

E-Z Reader's account of the interaction between oculomotor and cognitive processes depends critically on distinguishing between early and late stages of lexical processing, because this distinction allows saccadic programming to be decoupled from shifts of attention. Precisely specifying the nature of this distinction has important implications both for current models of lexical retrieval and for the development of E-Z Reader 8.