tbuckley/cabot-search huggingface dataset:
What activates visceral afferents?
Authors: D Grundy
Journal: Gut (2004)

Vagal and spinal afferents represent the information superhighways that convey sensory information from the gut to the central nervous system. These afferents are sensitive to both mechanical and chemical stimuli. Vagal afferents terminate in the muscle layers and in the mucosa. Muscle afferents are activated at physiological levels of distension and during peristalsis. In contrast, spinal afferents encode supraphysiological levels of intestinal pressure. Vagal and spinal afferents also express a wide range of membrane receptors to a variety of chemical mediators generated from both within and outside the gut wall. Some of these receptors are part of a modality specific transduction pathway involved in sensory signalling from the gut lumen to vagal afferent endings in the mucosa. Others, which are activated by substances derived from multiple cellular sources during ischaemia, injury, or inflammation act in a synergistic way to cause acute or chronic sensitisation of the afferent nerves to mechanical and chemical stimuli. Understanding the mechanisms that underlie hypersensitivity may have implications for the pharmaceutical approach to the treatment of functional bowel disorders like irritable bowel syndrome.
BILIARY EXCRETION OF RADIOACTIVE IRON AND TOTAL IRON AS INFLUENCED BY RED CELL DESTRUCTION
Authors: W. B. Hawkins, P. F. Hahn
Journal: The Journal of Experimental Medicine (1944)

Iron is eliminated in the bile of normal dogs at a low but quite constant rate, 0.2 mg. per day. The feeding of large amounts of iron to normal dogs does not cause an increased iron excretion in the bile nor does the injection of considerable quantities of colloidal iron by vein. When red cell destruction is brought about by acetyl-phenylhydrazine the elimination of biliary iron may increase tenfold and parallels the increased output of bile pigment. When red cells containing radioactive iron are destroyed by acetyl-phenylhydrazine there is a significant increase in radioactive iron excreted in the bile which parallels the bile pigment excretion-Charts A and C. The excretion of iron and bile pigment is independent of the volume of bile. When hemoglobin is destroyed the pigment radicle is totally excreted as bile pigment but only 3 per cent of the released iron is eliminated in the bile with conservation of the remainder. The importance of the liver and spleen as storehouses of iron is again confirmed. The body conserves iron even when it is present in marked excess.
Simulated-daylight photodynamic therapy with BF-200 aminolaevulinic acid for actinic keratosis: assessment of the efficacy and tolerability in a retrospective study
Authors: C. Kellner, S. Bauriedl, S. Hollstein, U. Reinhold
Journal: British Journal of Dermatology (2014)

Journal Article Simulated‐daylight photodynamic therapy with BF‐200 aminolaevulinic acid for actinic keratosis: assessment of the efficacy and tolerability in a retrospective study Get access C. Kellner, C. Kellner Dermatology Center Bonn Friedensplatz Bonn Germany Search for other works by this author on: Oxford Academic Google Scholar S. Bauriedl, S. Bauriedl Dermatology Center Bonn Friedensplatz Bonn Germany Search for other works by this author on: Oxford Academic Google Scholar S. Hollstein, S. Hollstein Dermatology Center Bonn Friedensplatz Bonn Germany Search for other works by this author on: Oxford Academic Google Scholar U. Reinhold U. Reinhold Dermatology Center Bonn Friedensplatz Bonn Germany Correspondence: Uwe Reinhold. E‐mail: u.reinhold@derma-bonn.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 4, 1 April 2015, Pages 1146–1148, https://doi.org/10.1111/bjd.13420 Published: 01 April 2015
Somatic<i>STAT3</i>Mutations in Large Granular Lymphocytic Leukemia
Authors: Hanna L.M. Koskela, Samuli Eldfors, Pekka Ellonen, Arjan J. van Adrichem, Heikki Kuusanmäki, Emma I. Andersson, Sonja Lagström, Michael J. Clemente, Thomas Olson, Sari E. Jalkanen, Muntasir Mamun Majumder, Henrikki Almusa, Henrik Edgren, Maija Lepistö, Pirkko Mattila, Kathryn Guinta, Pirjo Koistinen, Taru Kuittinen, Kati Penttinen, Alun Parsons, Jonathan Knowles, Janna Saarela, Krister Wennerberg, Olli Kallioniemi, Kimmo Porkka, Thomas P. Loughran, Caroline A. Heckman, Jaroslaw P. Maciejewski, Satu Mustjoki
Journal: New England Journal of Medicine (2012)

T-cell large granular lymphocytic leukemia is a rare lymphoproliferative disorder characterized by the expansion of clonal CD3+CD8+ cytotoxic T lymphocytes (CTLs) and often associated with autoimmune disorders and immune-mediated cytopenias.
Hepatocyte growth factor signaling pathway inhibits cholesterol 7α-hydroxylase and bile acid synthesis in human hepatocytes
Authors: Kwang-Hoon Song, Ewa Ellis, Stephen Strom, John Y.L. Chiang
Journal: Hepatology (2007)

Bile acid synthesis in the liver is regulated by the rate-limiting enzyme cholesterol 7alpha-hydroxylase (CYP7A1). Transcription of the CYP7A1 gene is inhibited by bile acids and cytokines. The rate of bile acid synthesis is reduced immediately after partial hepatectomy and during the early stage of liver regeneration. Hepatocyte growth factor (HGF) released from stellate cells activates a receptor tyrosine kinase c-Met, in hepatocytes and stimulates signaling pathways that regulate cell growth, proliferation, and apoptosis. This study demonstrated that HGF strongly and rapidly repressed CYP7A1 mRNA expression and the rate of bile acid synthesis in primary human hepatocytes. HGF rapidly induced c-Jun and small heterodimer partner mRNA and protein expression and increased phosphorylation of ERK1/2, JNK, and c-Jun. Specific inhibitors of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) blocked HGF inhibition of CYP7A1 expression. Knockdown of c-Met by small interfering RNA resulted in a significant increase in CYP7A1 and blocked HGF inhibition of CYP7A1 mRNA expression. Chromatin immunoprecipitation assays showed that HGF induced recruitment of c-Jun and small heterodimer partner (SHP) but reduced recruitment of the coactivators peroxisome proliferators activated receptor rho coactivator 1alpha (PGC-1alpha) and cAMP response element binding protein (CREB)-binding protein (CBP) to chromatin.This study demonstrated that HGF is a novel regulator of CYP7A1 and bile acid synthesis in human hepatocytes and may protect hepatocytes from accumulating toxic bile acids and developing intrahepatic cholestasis during the early stage of liver regeneration.
Collagen accumulation in heart ventricles as a function of growth and aging
Authors: M. EGHBALI, M. EGHBALI, T. F ROBINSON, S. SEIFTER, O. O BLUMENFELD
Journal: Cardiovascular Research (1989)

Increase in resting tension of left ventricular papillary muscle with age has been attributed to the amount of collagen present. We therefore studied the total amount and structure of myocardial collagen as a function of age in the hearts of male Fischer 344 rats. Using amino acid analysis and quantification of hydroxyproline, we showed that collagen accumulates in relation to ventricular protein after 3 months of age and continues in that mode with increased age of the animal, levelling off at 22 months. In this strain of rats, collagen increased in the left ventricle from 5.5% of total protein in a 1 month old animal to approximately 12% in 22 and 26 month old animals; in the right ventricle the increase was from 7% in the 1 month old animal to approximately 19.5% in 22-26 month old animals. The larger percentages of collagen in the right ventricle relative to the left agree with findings of others. Collagen accumulates in intrinsic collagenous structures where the pre-existing fibres are thickened and are more extensive. These structures were detected with light microscopy and scanning electron microscopy and include perimysial weaves, coiled perimysial fibres and struts. Regions of fibrosis were also increased in size and volume in older animals.
The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Antibodies against uncitrullinated peptides seem to occur prior to the antibodies to the corresponding citrullinated peptides
Authors: Mikael Brink, Monika Hansson, Johan Rönnelid, Lars Klareskog, Solbritt Rantapää Dahlqvist
Journal: Annals of the Rheumatic Diseases (2014)

The autoantibody repertoire in periodontitis : a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Antibodies against uncitrullinated peptides seem to occur prior to the antibodies to the corresponding citrullinated peptides
Impact of preoperative weight loss and body composition changes on postoperative outcome in surgery for inflammatory bowel disease.
Authors: C S Higgens, M R Keighley, R N Allan
Journal: Gut (1984)

One hundred and twenty seven patients undergoing elective surgery for inflammatory bowel disease were divided into three groups according to their preoperative ideal body weight (less than 80%, 80-90%, and greater than 90%). The groups were well matched in respect of age, sex, corticosteroid therapy, pre-existing sepsis, peroperative antimicrobial chemotherapy, and resection site. None received peroperative nutritional support. The postoperative outcome was similar in each of the three nutritional groups including the incidence of postoperative sepsis, duration of hospital stay, and mortality. Serial peroperative changes in weight, fat, and muscle bulk were assessed by anthropometric measurements in 21 of these patients. The deficits in weight, fat, and muscle bulk were similar at 10 and 21 days postoperatively in the three groups. At 84 days those malnourished preoperatively had recovered their nutritional status faster than the well nourished patients. We conclude that in these patients undergoing elective resection for inflammatory bowel disease preoperative weight loss did not adversely affect the postoperative outcome.
Sex and limb differences in hip and knee kinematics and kinetics during anticipated and unanticipated jump landings: implications for anterior cruciate ligament injury
Authors: T N Brown, R M Palmieri-Smith, S G McLean
Journal: British Journal of Sports Medicine (2009)

In this study, the effects of temporal changes in unanticipated (UN) prelanding stimuli on lower limb biomechanics and the impact of sex and limb dominance on these variables during single-leg landings were determined. It was hypothesised that reductions in the time of prelanding UN stimuli, female sex, and the non-dominant limb would significantly increase high-risk landing biomechanics during UN jump landings.26 (13 men and 13 women) had initial contact (IC) and peak stance (0-50%) phase (PS) lower limb joint kinematics and kinetics quantified during anticipated (AN) and UN single-leg (left and right) landings. Postlanding jump direction was governed via one of two randomly ordered light stimuli, presented either before initiation of the jump (AN), or 600 ms (UN1), 500 ms (UN2) or 400 ms (UN3) immediately before ground contact.Statistically significant (p<0.05) differences in IC hip posture and PS hip and knee internal rotation moments occurred in UN compared with AN landings. Differences were not observed, however, among UN conditions for any biomechanical comparisons. Significant (p<0.05) differences in specific IC and PS hip and knee postures and loads occurred between sexes and limbs. Neither of these factors, however, influenced movement condition effects.UN landings induce modifications in landing biomechanics that may increase anterior cruciate ligament injury risk in both men and women. These modifications, however, do not appear overly sensitive to the timing of the UN stimulus, at least within a temporal range affording a successful movement response. Expanding UN training to include even shorter stimulus-response times may promote the additional central control adaptations necessary to manoeuvre safely within the random sports setting.
Pulmonary atresia with left ventricular-right atrial communication: basis for circular shunt.
Authors: K L Jue, G Noren, J E Edwards
Journal: Thorax (1966)

In the usual instance of an intracardiac right-to- left shunt the blood participating in the shunt traverses a capillary bed before it returns to the chamber from which it originated.In an uncommon instance some of the shunted blood returns to the chamber of origin through intra- cardiac channels, yielding a phenomenon which may be termed a 'circular' shunt.This term was first used with reference to a case reported from our group by Shone, Anderson, Elliott, Amplatz, Lillehei, and Edwards (1962).In that case it was assumed that some of the right atrial blood had been shunted in a right-to-left direction into the left atrium.Some of this blood then escaped from the left ventricle through a small ventricular septal defect into the right ventricle.Then, in the presence of pulmonary stenosis and of tricuspid insufficiency, some of the blood which had originated in the right atrium returned to that chamber to complete a 'circular' shunt in which each of the four cardiac chambers had participated.We have studied two additional cases which fulfil the foregoing definition of a 'circular' shunt.In each there was pulmonary valvular atresia in association with a left ventricular-right atrial communication.In the first, the left ventricular- right atrial communication was of the classical variety.In the second, this communication resulted from a combination of Ebstein's mal- formation of the tricuspid valve and a ventricular septal defect in which the defect opened into that part of the right ventricle which lay proximal to the attachments of the malformed tricuspid valve.
Naproxen sodium and piroxicam in acute musculo-skeletal disorders.
Authors: T. A. Bouchier-Hayes
Journal: British Journal of Sports Medicine (1984)

Of one hundred patients originally entered for this trial eighty-three with acute musculo-skeletal disorders were treated with either naproxen sodium (SYNFLEX, Syntex), 550 mg initially followed by 275 mg four times daily, or piroxicam (FELDENE, Pfizer), 20 mg twice daily for two days then 20 mg once daily. Patients were assessed at admission, on day 4 and on day 8. Pain on passive movement, tenderness, swelling and limitation of function were evaluated and patients also completed a daily self-assessment form. Pain relief was recorded by the patient for 4 hours following the first dose. No statistically significant differences were detected between the treatment groups for any of the efficacy measurements. Of the eighty-three patients analysed, twenty-four patients withdrew from treatment twenty of whom did not need further analgesia (13 in the naproxen sodium group and 7 in the piroxicam group). Three patients experienced side-effects; all were in the piroxicam group, and one patient withdrew from the study because of epigastric pain. Both naproxen sodium and piroxicam proved effective in the treatment of musculo-skeletal disorders. Naproxen sodium did not give rise to any side-effects.
Massive Hepatic Necrosis in a Patient Receiving Allopurinol Concomitant Medication
Authors: S. MOHSIN Shah
Journal: JAMA (1977)

<h3>To the Editor.—</h3> In response to an inquiry, we welcome the opportunity to provide some important information not included in our article. "Massive Hepatic Necrosis in a Patient Receiving Allopurinol" (237:473, 1977). Concomitant medications included hydralazine hydrochloride, propranolol hydrochloride, and hydrochlorthiazide. The patient had been receiving these drugs intermittently for four years and continuously for the previous two years, with normal liver functions. This, and the strong temporal relationship between the initiation of allopurinol and the onset of the hypersensitivity reaction, convinced us that allopurinol was responsible for her death. Previous reports of severe allopurinol hypersensitivity have emphasized the association with thiazides.<sup>1</sup>Since thiazides cause hyperuricemia, the concomitant use of allopurinol is probably common. The association in cases of severe hypersensitivity may be coincidental.
Prognostic Relevance of Hypoglycemia Following an Oral Glucose Challenge for Cystic Fibrosis–Related Diabetes
Authors: Kerstin Radike, Katharina Molz, Reinhard W. Holl, Britta Poeter, Helge Hebestreit, Manfred Ballmann
Journal: Diabetes Care (2011)

An annual oral glucose tolerance test (OGTT) has become part of standard care in cystic fibrosis (CF) to screen for CF-related diabetes (CFRD) in patients older than 10 years of age (1). Up to 15% of patients with CF develop hypoglycemia during an OGTT (2), and there is some discussion whether such a response indicates an increased risk for the development of CFRD. In fact, a reactive hypoglycemia has been considered as an early stage of CFRD (3). However, the prognostic value of such a reactive hypoglycemia with respect to future glucose control has never been studied. Based on a delayed insulin secretion in CF, which might be relevant to both a hypoglycemic as well as a hyperglycemic response to a glucose challenge (4), we hypothesized that the hypoglycemic response to a glucose …
Cytochrome<i>P</i>450 Epoxygenase Promotes Human Cancer Metastasis
Authors: Jian-Gang Jiang, Yao-Gui Ning, Chen Chen, Ding Ma, Zhen-Jun Liu, Shilin Yang, Jianfeng Zhou, Xiao Xiao, Xin A. Zhang, Matthew L. Edin, Jeffrey W. Card, Jianing Wang, Darryl C. Zeldin, Dao Wen Wang
Journal: Cancer Research (2007)

Cytochrome P450 (CYP) epoxygenases convert arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EET), which exert diverse biological activities in a variety of systems. We previously reported that the CYP2J2 epoxygenase is overexpressed in human cancer tissues and cancer cell lines and that EETs enhance tumor growth, increase carcinoma cell proliferation, and prevent apoptosis of cancer cells. Herein, we report that CYP epoxygenase overexpression or EET treatment promotes tumor metastasis independent of effects on tumor growth. In four different human cancer cell lines in vitro, overexpression of CYP2J2 or CYP102 F87V with an associated increase in EET production or addition of synthetic EETs significantly induced Transwell migration (4.5- to 5.5-fold), invasion of cells (3- to 3.5-fold), cell adhesion to fibronectin, and colony formation in soft agar. In contrast, the epoxygenase inhibitor 17-ODYA or infection with the antisense recombinant adeno-associated viral vector (rAAV)-CYP2J2 vector inhibited cell migration, invasion, and adhesion with an associated reduction in EET production. CYP overexpression also enhanced metastatic potential in vivo in that rAAV-CYP2J2-infected MDA-MB-231 human breast carcinoma cells showed 60% more lung metastases in athymic BALB/c mice and enhanced angiogenesis in and around primary tumors compared with control cells. Lung metastasis was abolished by infection with the antisense rAAV-CYP2J2 vector. CYP epoxygenase overexpression or EET treatment up-regulated the prometastatic matrix metalloproteinases and CD44 and down-regulated the antimetastatic genes CD82 and nm-23. Together, these data suggest that CYP epoxygenase inhibition may represent a novel approach to prevent metastasis of human cancers.
Role of Phosphodiesterase 3 in NO/cGMP-Mediated Antiinflammatory Effects in Vascular Smooth Muscle Cells
Authors: Toru Aizawa, Heng Wei, Joseph M. Miano, Jun-ichi Abe, Bradford C. Berk, Chen Yan
Journal: Circulation Research (2003)

Atherosclerosis involves cellular immune responses and altered vascular smooth muscle cell (VSMC) function. Nitric oxide (NO)/cGMP is uniquely capable of inhibiting key processes in atherosclerosis. In this study, we determined the effects of NO/cGMP and their molecular mechanisms in the regulation of NF-kappaB-dependent gene expression in VSMCs. We found that cGMP-elevating agents such as the NO donor S-nitroso-N-acetylpenicillamine (SNAP) and C-type natriuretic peptide (CNP), reduced TNF-alpha-induced NF-kappaB-dependent reporter gene expression in rat aortic VSMCs in a cGMP-dependent manner. The effects of SNAP and CNP on NF-kappaB are mediated by cAMP-dependent protein kinase (PKA) but not cGMP-dependent protein kinase (PKG) based on the findings that the selective PKA inhibitor, PKI, abolished the effects of SNAP and CNP on NF-kappaB, whereas the PKG inhibitor Rp-8-Br-PET-cGMP had no effect. Inhibition of cGMP-inhibited cAMP-hydrolyzing phosphodiesterase 3 (PDE3) blocked SNAP- and CNP-elicited effects on NF-kappaB-dependent transcription. Furthermore, cGMP analogues such as 8-pCPT-cGMP, which selectively activates PKG but does not inhibit PDE3, had no effect on NF-kappaB-mediated transcription. Activation of PKA by SNAP or cAMP-elevating agents not only inhibited TNF-alpha-induced NF-kappaB-dependent reporter gene expression but also reduced endogenous NF-kappaB-dependent adhesion molecule and chemokine expression. These results suggest that SNAP and CNP exert inhibitory effects on NF-kappaB-dependent transcription by activation of PKA via cGMP-dependent inhibition of PDE3 activity. Therefore, PDE3 is a novel mediator of inflammation in VSMCs.
The role of humoral mucosal immunity in the induction and maintenance of chronic airway infections.
Authors: P Brandtzaeg
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The respiratory mucosa is protected primarily by a secretory immune system that is under complex and only partly understood immunoregulatory control. Secretory immunoglobulins (SIgA and SIgM) protect the mucosal surface by immune exclusion of antigens. However, the fact that most IgA produced in the respiratory tract belongs to the IgA1 subclass renders SIgA in this region susceptible to IgA-specific proteases produced by Haemophilus influenzae, Streptococcus pneumonia, and Neisseria meningitidis. Immunoglobulin G can also perform immune exclusion at respiratory surfaces but, like IgE, it reaches the secretions merely by passive diffusion. The phlogistic properties of antibodies belonging to these classes explain their potential involvement in maintaining mucosal inflammation. In patients with selective IgA deficiency, SIgA is lacking and is not regularly compensated for satisfactorily by SIgM. In such patients unexplained immunoregulatory mechanisms, perhaps involving the local microbiota, give rise to a large number of IgD-producing cells in the upper respiratory tract. Immunoglobulin D cannot act as a secretory antibody and might block the protective properties of IgG; this could explain why these patients are particularly prone to recurrent infections. Our observations show that there are large individual variations in the mucosal immune system with regard to humoral immunity in the upper respiratory tract.
Emotion-Related Self-Regulation and Its Relation to Children's Maladjustment
Authors: Nancy Eisenberg, Tracy L. Spinrad, Natalie D. Eggum
Journal: Annual Review of Clinical Psychology (2010)

The development of children's emotion-related self-regulation appears to be related to, and likely involved in, many aspects of children's development. In this review, the distinction between effortful self-regulatory processes and those that are somewhat less voluntary is discussed, and literature on the former capacities is reviewed. Emotion-related self-regulation develops rapidly in the early years of life and improves more slowly into adulthood. Individual differences in children's self-regulation are fairly stable after the first year or two of life. Such individual differences are inversely related to at least some types of externalizing problems. Findings for internalizing problems are less consistent and robust, although emotion-related self-regulation appears to be inversely related to internalizing problems after the early years. Self-regulatory capacities have been related to both genetic and environmental factors and their interaction. Some interventions designed to foster self-regulation and, hence, reduce maladjustment, have proved to be at least partially effective.