tbuckley/cabot-search huggingface dataset:
Inhibition of neutral endopeptidase 3.4.24.11 in conscious dogs with pacing induced heart failure
Authors: A. A Seymour, M. M Asaad, V. M Lanoce, S. A Fennell, H. S Cheung, W L. Rogers
Journal: Cardiovascular Research (1993)

The effects of a selective neutral endopeptidase inhibitor, SQ 28,603 (N-[2-(mercaptomethyl)-1-oxo-3-phenylpropyl]-beta-alanine), were determined in an experimental model of heart failure.The symptoms of heart failure were induced by rapid ventricular pacing for one or three weeks in dogs with surgically implanted catheters for measurement of atrial pressures and mean arterial pressure and with ultrasonic flow probes for determination of cardiac output and renal blood flow.Inhibition of neutral endopeptidase by 10, 30, or 100 mumol.kg-1 SQ 28,603 given intravenously increased sodium excretion, cyclic GMP excretion, and plasma concentrations of atrial natriuretic peptide in a dose related manner in conscious dogs paced for one week. SQ 28,603 (100 mumol.kg-1) stimulated similar natriuretic and cyclic GMP responses in dogs paced for three weeks although baseline glomerular filtration rate was reduced. Because the natriuresis was maintained despite the smaller filtered sodium load, the increase in fractional sodium excretion was significantly greater after three weeks of pacing (from 0.5(0.2) to 3.7(0.7)%) than after one week of tachycardia (from 0.1(0.0) to 2.0(0.3)%). By contrast, SQ 28,603 (100 mumol.kg-1) did not affect renal, haemodynamic, or hormonal variables in normal conscious dogs where baseline atrial natriuretic peptide (18(3) fmol.ml-1) was lower than in the paced animals (104(10) fmol.ml-1).Inhibition of neutral endopeptidase in dogs with pacing induced heart failure protected endogenous atrial natriuretic peptide from degradation and stimulated sustained natriuresis, presumably via a tubular mechanism.
Ratio of visceral fat to subcutaneous fat area is a predictive biomarker for complicated crohn's disease
Authors: V. Subramanian, B. Erhayiem, R. Dhingsa, C. J. Hawkey
Journal: Gut (2011)

<h3>Introduction</h3> Fat wrapping and mesenteric hypertrophy are considered hallmarks of Crohn9s disease (CD). Mesenteric adipose tissue in patients with CD has been shown to release higher levels of adiponectin, which could result in upregulated production of TNF-α and increased risk of developing more aggressive disease. We aimed to study if a higher visceral to abdominal fat ratio was associated with more aggressive subtypes (fistulating or stricturing) of CD. <h3>Methods</h3> We identified patients with a confirmed diagnosis of CD and selected patients who had had CT scans of their abdomen. Subcutaneous and visceral fat areas were measured in one cross-sectional scan taken at the level of the umbilicus. The mesenteric fat index (MFI) defined as a ratio of visceral to subcutaneous fat area. The MFI was compared between patients with complicated Crohn9s (strictures and fistulas) and inflammatory Crohn9s (non-stricturing and non-penetrating). <h3>Results</h3> CT scans from 50 patients with CD were evaluated. The mean age of the patients with complications (n=29) was 37.7±14.9 years and in patients with no complications (n=21) was 30.1±18.3 years. The MFI was significantly higher (p=0.001) in patients with complicated disease (0.67±0.29) than in those with uncomplicated disease (0.23±0.10) and was the only variable that remained significantly different on multivariate analysis. The area under the receiver operating curve for the MFI was 0.95 (95%CI 0.89 to 1.0) and an MFI of 0.29 was 93% sensitive and 81% specific in detecting patients with complicated CD. <h3>Conclusion</h3> Higher MFI is indicative of more aggressive fistulating and stricturing subtypes of CD. Further work is needed to address whether this is a primary or secondary phenomenon.
SynGAP: a Synaptic RasGAP that Associates with the PSD-95/SAP90 Protein Family
Authors: Jee Hae Kim, Dezhi Liao, Lit-Fui Lau, Richard L Huganir
Journal: Neuron (1998)

The PSD-95/SAP90 family of proteins has recently been implicated in the organization of synaptic structure. Here, we describe the isolation of a novel Ras-GTPase activating protein, SynGAP, that interacts with the PDZ domains of PSD-95 and SAP102 in vitro and in vivo. SynGAP is selectively expressed in brain and is highly enriched at excitatory synapses, where it is present in a large macromolecular complex with PSD-95 and the NMDA receptor. SynGAP stimulates the GTPase activity of Ras, suggesting that it negatively regulates Ras activity at excitatory synapses. Ras signaling at the postsynaptic membrane may be involved in the modulation of excitatory synaptic transmission by NMDA receptors and neurotrophins. These results indicate that SynGAP may play an important role in the modulation of synaptic plasticity.
TRPC1 Channels Are Critical for Hypertrophic Signaling in the Heart
Authors: Malini Seth, Zhu-Shan Zhang, Lan Mao, Victoria Graham, Jarrett Burch, Jonathan Stiber, Leonidas Tsiokas, Michelle Winn, Joel Abramowitz, Howard A. Rockman, Lutz Birnbaumer, Paul Rosenberg
Journal: Circulation Research (2009)

Rationale: Cardiac muscle adapts to increase workload by altering cardiomyocyte size and function resulting in cardiac hypertrophy. G protein–coupled receptor signaling is known to govern the hypertrophic response through the regulation of ion channel activity and downstream signaling in failing cardiomyocytes. Objective: Transient receptor potential canonical (TRPC) channels are G protein–coupled receptor operated channels previously implicated in cardiac hypertrophy. Our objective of this study is to better understand how TRPC channels influence cardiomyocyte calcium signaling. Methods and Results: Here, we used whole cell patch clamp of adult cardiomyocytes to show upregulation of a nonselective cation current reminiscent of TRPC channels subjected to pressure overload. This TRPC current corresponds to the increased TRPC channel expression noted in hearts of mice subjected to pressure overload. Importantly, we show that mice lacking TRPC1 channels are missing this putative TRPC current. Moreover, Trpc1 − / − mice fail to manifest evidence of maladaptive cardiac hypertrophy and maintain preserved cardiac function when subjected to hemodynamic stress and neurohormonal excess. In addition, we provide a mechanistic basis for the protection conferred to Trpc1 − / − mice as mechanosensitive signaling through calcineurin/NFAT, mTOR and Akt is altered in Trpc1 − / − mice. Conclusions: From these studies, we suggest that TRPC1 channels are critical for the adaptation to biomechanical stress and TRPC dysregulation leads to maladaptive cardiac hypertrophy and failure.
Diagnosis and management of right ventricle-dependent coronary circulation in pulmonary atresia with intact ventricular septum.
Authors: T M Giglia, V S Mandell, A R Connor, J E Mayer, J E Lock
Journal: Circulation (1992)

BACKGROUND Coronary artery anomalies including 1) right ventricle (RV)-to-coronary artery fistulas, 2) coronary artery stenoses, and 3) coronary occlusions occur in patients with pulmonary atresia with intact ventricular septum (PA-IVS). In some, a large part of the coronary blood supply may depend on the RV. This RV-dependent coronary circulation may determine survival after right ventricular decompression (RVD): RVD may cause RV "steal" in the presence of fistulas alone and ischemia, coronary isolation, or myocardial infarction in the presence of coronary stenoses. METHODS AND RESULTS Eighty-two patients with PA-IVS who presented between January 1979 and January 1990 were reviewed; 26 (32%) had RV-to-coronary artery fistulas. Of these 26, 23 had adequate preoperative coronary angiograms for analysis. RVD was achieved in 16. Seven of 16 had fistulas only; each survived RVD. Six of 16 had stenosis of a single coronary artery [left anterior descending coronary artery (LAD), four; right coronary artery (RCA), two]; four of six survived RVD. Three of 16 had stenoses and/or occlusion of both the RCA and LAD; all three died shortly after RVD of acute left ventricular dysfunction. CONCLUSIONS 1) Potential RV steal alone does not preclude successful RVD. 2) Fistulas with stenoses to a single coronary artery may not preclude successful RVD. 3) RVD appears to be contraindicated in the presence of stenoses and/or occlusion involving both the right and left coronary systems. Nonsurvival after RVD seems to depend on the amount of the left ventricular myocardium at risk, i.e., that which is distal to coronary artery stenoses, especially when involvement of both coronary arteries limits effective collateralization. Precise definition of coronary arterial anatomy is mandatory in neonates with PA-IVS.
Infection and inflammation in liver failure: Two sides of the same coin
Authors: Raza Malik, Rajeshwar P. Mookerjee, Rajiv Jalan
Journal: Journal of Hepatology (2009)

Acute deterioration in the clinical condition of a cirrhotic patient due to the effects of a precipitating illness leading to hospital admission is associated with widely variable clinical outcomes. A proportion of patients makes an appropriate response to treatment of the precipitating event and can be discharged relatively quickly from hospital. There are a second group of patients, who despite treatment of the precipitating event progress to organ dysfunction, developing complications of cirrhosis and this is the group that is associated with high mortality rates and is referred to broadly as ‘Acute on Chronic Liver Failure’ (ACLF) [1].
Abstract 2171: Viral infection as an etiological risk factor for diffuse large B cell lymphoma (DLBCL): A comparative study between Egypt and Sweden
Authors: Therese AS Jacobson, Abeer A. Bahnassy, Ali Moshfeg, Abdel Rahman N. Zekri, Anna Porwit Porwit, Joachim Lundahl, Nadia M. Mokhtar, Nayera A. Abdel-Hamid, hussein M. Khaled, Håkan Mellstedt
Journal: Cancer Research (2010)

Abstract Objective: Previous studies have reported an association between increased risk of diffuse large B cell lymphoma (DLBCL) and hepatitis B, hepatitis C, Epstein Barr viruses infection in some countries including Egypt. We therefore assume that the progression of DLBCL might be enhanced by chronic viral infection and that specific pathways can be targeted for the prevention and therapy of DLBCL. Our aim is to assess the possible role of viral infections in the development and progression of DLBCL by determining the genetic profile of DLBCL cases from areas with different prevalence of viral infection. Methods: Gene expression profile of well-characterized cases of DLBCL (30 from Egypt and 16 from Sweden) together with their normal matched controls was studied using the Affymetrix Human GeneShip U133 plus 2.0. Data sets were assigned to two groups (Swedish and Egyptian) and the expression profiles were compared to identify genes that were differentially expressed between the groups. Lists were compiled of all genes for which expression was differentially either induced or suppressed &amp;gt;2-fold between groups. The gene lists were categorized according to their biological functions as described in GeneSpring and Ingenuity. Validation studies were done using RT-PCR, in situ hybridization and immunohistovhemistry. Results: After statistical analysis and filtration by fold change more than 2 times, 2790 genes entities were differentially expressed in the two groups. 1) STAT 2 was highly expressed in Swedish patients and the difference between the two patient groups is clearly indicated in the IFN signaling pathway, 2) higher expression of antigen presentation gene in Egyptian patients compared to Swedish patients (HLA-DQA1, HLA-B, MHCIIα, MHCIα), and 3) higher expression genes in wnt signaling pathway in Egyptian patients compared to Swedish patients (wnt7A, β catenine, CK1). Conclusions: Chronic viral infection could be a risk factor for DLBCL in Egypt (which represents an area with high prevalence of viral infection) but not in Sweden. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2171.
Sodium Salicylate for Arthritis
Authors: Armand J. Quick
Journal: JAMA (1974)

<h3>To the Editor.—</h3> On reading the comments on new drugs supplementing aspirin in treating arthritis (229:505, 1974), no mention was made of sodium salicylate in the treatment of inflammatory arthritis. It seems to have been forgotten that prior to the introduction of aspirin into therapy in 1899, sodium salicylate was successfully employed in treating acute rheumatic fever and also inflammatory rheumatism. No satisfactory explanation has ever been offered why aspirin has so completely replaced sodium salicylate in therapy. At the International Symposium on Salicylates in 1962,<sup>1</sup>it was stated that sodium salicylates possess certain unpleasant side effects, notably gastric disturbance, and that many patients develop a strong aversion to the tests. This has not been my experience, either in years of experimental study nor in the clinical employment of sodium salicylate. The acetylation of salicylic acid, which produces aspirin, definitely potentiates the analgesic action of salicylic acid, thus making
Successful endoscopic treatment for Mirizzi syndrome type II under direct peroral cholangioscopy using an ultraslim upper endoscope
Authors: Dong Kim, Jong Moon, Hyun Choi, Moon Choi, Tae Lee, Sang-Woo Cha
Journal: Endoscopy (2014)

Surgery is standard management for patients with Mirizzi syndrome. In cases of Mirizzi syndrome type II, laparoscopic surgery is even more complicated because of the cholecystocholedochal fistula. Endoscopic treatment for Mirizzi syndrome is still controversial except to relieve a bile duct obstruction [1] [2]. This report describes a successful endoscopic treatment for Mirizzi syndrome type II with laser lithotripsy under direct peroral cholangioscopy (POC) using an ultraslim upper endoscope.
Breast cancer in women with primary biliary cirrhosis.
Authors: B M Goudie, A D Burt, P Boyle, G Macfarlane, G G Birnie, P R Mills, C R Gillis, R N MacSween, G Watkinson
Journal: BMJ (1985)

The occurrence of extrahepatic malignancy was studied in 195 unselected patients who satisfied predetermined biochemical, immunological, and histological criteria for the diagnosis of primary biliary cirrhosis. The incidence of breast cancer in women with primary biliary cirrhosis was found to be significantly higher than in an age and sex matched control population from the same well defined geographical area (p less than 0.0015). The association of breast cancer and primary biliary cirrhosis remains unexplained, though diminished immunological surveillance, fat soluble vitamin deficiency, or endocrine dysfunction may play a part.
Alternative Treatments of Vasomotor Symptoms of Menopause
Authors: Baoming Ge
Journal: Annals of Internal Medicine (2007)

Letters4 September 2007Alternative Treatments of Vasomotor Symptoms of MenopauseBaoming Ge, MD, MClScBaoming Ge, MD, MClScFrom China Clinical Trial Coordination Center, Beijing 100025, China.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-147-5-200709040-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read the paper on Newton and colleagues' excellent work (1) with great interest. My study group has just finished a pilot study of a black cohosh ethanol extract in Beijing, China, and we are on track to conduct a nationwide, multicenter, randomized, controlled trial. The double-blind pilot study enrolled 120 Chinese women with climacteric symptoms who were stratified into perimenopausal and postmenopausal groups, according to the standard of STRAW (Stages of Reproductive Aging Workshop). We divided each group into 3 intervention groups—low-dose black cohosh (1 pill twice daily), high-dose black cohosh (1 pill thrice daily), and ...References1. Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006;145:869-79. [PMID: 17179056] LinkGoogle Scholar2. Altman DG, Bland JM. Absence of evidence is not evidence of absence. BMJ. 1995;311:485. [PMID: 7647644] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From China Clinical Trial Coordination Center, Beijing 100025, China.Disclosures: Dr. Ge is the medical director of a clinical research organization, China Clinical Trial Coordination Center, Beijing, China. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTreatment of Vasomotor Symptoms of Menopause with Black Cohosh, Multibotanicals, Soy, Hormone Therapy, or Placebo Katherine M. Newton , Susan D. Reed , Andrea Z. LaCroix , Louis C. Grothaus , Kelly Ehrlich , and Jane Guiltinan Alternative Treatments of Vasomotor Symptoms of Menopause Jonathan R. Byron Alternative Treatments of Vasomotor Symptoms of Menopause Katherine M. Newton , Susan D. Reed , and Andrea Z. LaCroix Alternative Treatments of Vasomotor Symptoms of Menopause Jonathan P. Krueger Metrics Cited ByBlack cohosh…a cautionary tale! 4 September 2007Volume 147, Issue 5Page: 346KeywordsAdverse eventsAgingClinical trialsConflicts of interestEthanolHormone replacement therapyMenopausePilot studiesSafetySafety studies ePublished: 4 September 2007 Issue Published: 4 September 2007 CopyrightCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Inhibition of natural killer cells protects the liver against acute injury in the absence of glycine N-methyltransferase
Authors: Laura Gomez-Santos, Zigmund Luka, Conrad Wagner, Sara Fernandez-Alvarez, Shelly C. Lu, Jose M. Mato, Maria L. Martinez-Chantar, Naiara Beraza
Journal: Hepatology (2012)

Glycine N-methyltransferase (GNMT) catabolizes S-adenosylmethionine (SAMe), the main methyl donor of the body. Patients with cirrhosis show attenuated GNMT expression, which is absent in hepatocellular carcinoma (HCC) samples. GNMT−/− mice develop spontaneous steatosis that progresses to steatohepatitis, cirrhosis, and HCC. The liver is highly enriched with innate immune cells and plays a key role in the body's host defense and in the regulation of inflammation. Chronic inflammation is the major hallmark of nonalcoholic steatohepatitis (NASH) progression. The aim of our study was to uncover the molecular mechanisms leading to liver chronic inflammation in the absence of GNMT, focusing on the implication of natural killer (NK) / natural killer T (NKT) cells. We found increased expression of T helper (Th)1- over Th2-related cytokines, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-R2/DR5, and several ligands of NK cells in GNMT−/− livers. Interestingly, NK cells from GNMT−/− mice were spontaneously activated, expressed more TRAIL, and had strong cytotoxic activity, suggesting their contribution to the proinflammatory environment in the liver. Accordingly, NK cells mediated hypersensitivity to concanavalin A (ConA)-mediated hepatitis in GNMT−/− mice. Moreover, GNMT−/− mice were hypersensitive to endotoxin-mediated liver injury. NK cell depletion and adoptive transfer of TRAIL−/− liver-NK cells protected the liver against lipopolysaccharide (LPS) liver damage. Conclusion: Our data allow us to conclude that TRAIL-producing NK cells actively contribute to promote a proinflammatory environment at early stages of fatty liver disease, suggesting that this cell compartment may contribute to the progression of NASH. (HEPATOLOGY 2012)
Kupffer cell and interleukin-12-dependent loss of natural killer T cells in hepatosteatosis
Authors: Michael Kremer, Emmanuel Thomas, Richard J. Milton, Ashley W. Perry, Nico van Rooijen, Michael D. Wheeler, Steven Zacks, Michael Fried, Richard A. Rippe, Ian N. Hines
Journal: Hepatology (2009)

Hepatosteatosis is associated with increased expression of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-12, major T helper (Th) 1 cytokines, and reduced hepatic natural killer T (NKT) cell numbers. The relationship between lipid accumulation, cytokine expression, and hepatic NKT cells is not known. This study was conducted to assess the role of IL-12 in the development of hepatic steatosis and its potential impact on liver NKT cells. Male C57Bl/6 wildtype (WT) and IL-12-deficient (IL-12(-/-)) mice were fed a choline-deficient diet (CDD) for 0, 10, or 20 weeks. CDD led to marked hepatosteatosis, reduced hepatic but not splenic NKT cell numbers and function, and increased hepatic expression of the T(h)1-type cytokines IL-12, interferon gamma (IFN-gamma), and TNF-alpha in WT mice. The absence of IL-12 resulted in similar CDD-induced hepatosteatosis, but preserved hepatic NKT cells and significantly reduced hepatic IFN-gamma and TNF-alpha expression. Treatment of CDD-fed mice with lipopolysaccharide led to a significant increase in hepatic IL-12 expression, and Kupffer cell (KC) depletion reduced liver IL-12 expression and restored NKT cells in CDD-induced fatty liver. Interestingly, KCs from CDD-fed mice failed to produce increased quantities of IL-12 upon activation in vitro when compared to similarly treated KCs from control fed mice, suggesting that secondary factors in vivo promote heightened IL-12 production. Finally, human livers with severe steatosis showed a substantial decrease in NKT cells.Hepatosteatosis reduces the numbers of hepatic NKT cells in a KC-and IL-12-dependent manner. Our results suggest a pivotal and multifunctional role of KC-derived IL-12 in the altered immune response in steatotic liver, a process that is likely active within human nonalcoholic fatty liver disease.
1171 ROLE OF IRON METABOLISM IN CHRONIC HEPATITIS C TREATMENT
Authors: M. Nakamuta, M. Kohjima, Y. Shimonaka, R. Yada, A. Taketomi, K. Gotoh, T. Yoshimoto, N. Fukushima, K. Fukuizumi, K. Kawabe, T. Mizutani, N. Harada, S. Morizono, Y. Maehara, M. Enjoji
Journal: Journal of Hepatology (2011)
Comparison of the adrenal and renal responses to angiotensin II fetal lambs and adult sheep.
Authors: J E Robillard, R A Gomez, D VanOrden, F G Smith
Journal: Circulation Research (1982)

The adrenal and renal responses to similar increases in plasma angiotensin II (AII) were studied in chronically catheterized fetal lambs (112-131 days gestation: term 145 days) and adult nonpregnant sheep. The rate of AII infusion was adjusted to compare the effect of similar rises in plasma AII concentration between fetuses and adult ewes. Increases in plasma AII were associated with a decrease in plasma renin activity (PRA) in both fetuses (5.55 +/- 1.53 to 2.11 +/- 0.59 ng/ml per hr, P less than 0.05) and adult ewes (1.28 +/- 0.34 to 0.62 +/- 0.16 ng/ml per hr, P less than 0.05), but the percent changes in PRA for similar increases in plasma AII were not different when fetuses were compared to adult ewes. Contrary to the effect of AII on PRA, the increase in plasma AII did not produce parallel changes in plasma aldosterone concentration when fetuses were compared to adult ewes. The percent changes in plasma aldosterone concentration for similar increases in AII concentration were significantly higher in adult ewes (+165 +/- 37%) than in fetuses (+58 +/- 15%)(P less than 0.01). Finally, there were no significant changes in fetal urinary excretion of PGE and PGF2alpha when a significant rise (P less than 0.05) was observed in adult ewes at the highest level of plasma AII concentration. In summary, the present results tend to suggest that there are differences between fetuses and adult ewes in the response to AII, the response being smaller in fetuses.