tbuckley/cabot-search huggingface dataset:
Autoimmune cholangiopathy: Part of the spectrum of autoimmune chronic active hepatitis
Authors: Ziv Ben-Ari, Amar Paul Dhillon, Sheila Sherlock
Journal: Hepatology (1993)

We describe four patients with features overlapping those of primary biliary cirrhosis and autoimmune chronic active hepatitis. Three were female and one was male; only one was symptomatic. Serum biochemical study showed increases in alkaline phosphatase and alpha-glutamyltranspeptidase levels. Markers of hepatitis B and C viruses were absent. In all four patients, serum mitochondrial antibodies could not be detected on immunofluorescence study and serum M2 antibodies were absent. All four patients had high titers of serum antinuclear antibody of diffuse type. Serum actin antibodies were detected in all four patients. Liver biopsy specimens showed histological features of primary biliary cirrhosis, with marked cellular infiltration of the portal areas and bile duct damage. Intralobular inflammation and piecemeal necrosis were mild. Three patients were treated with prednisolone and showed rapid clinical and biochemical remission. Serial liver biopsy specimens showed reduced inflammation, but bile duct lesions persisted. These patients probably form a subgroup of autoimmune chronic active type 1 with predominant bile duct damage. The subgroup might be termed autoimmune cholangiopathy.
Monkeys in space: Primate neural data suggest volumetric representations
Authors: Sidney R. Lehky, Anne B. Sereno, Margaret E. Sereno
Journal: Behavioral and Brain Sciences (2013)

The target article does not consider neural data on primate spatial representations, which we suggest provide grounds for believing that navigational space may be three-dimensional rather than quasi-two-dimensional. Furthermore, we question the authors' interpretation of rat neurophysiological data as indicating that the vertical dimension may be encoded in a neural structure separate from the two horizontal dimensions.
Long-Term Ambrisentan Therapy for the Treatment of Pulmonary Arterial Hypertension
Authors: Ronald J. Oudiz, Nazzareno Galiè, Horst Olschewski, Fernando Torres, Adaani Frost, Hossein A. Ghofrani, David B. Badesch, Michael D. McGoon, Vallerie V. McLaughlin, Ellen B. Roecker, Brooke C. Harrison, Darrin Despain, Christopher Dufton, Lewis J. Rubin
Journal: Journal of the American College of Cardiology (2009)
Are there differences in postural regulation according to the level of competition in judoists?
Authors: T Paillard, C Costes-Salon, C Lafont, P Dupui
Journal: British Journal of Sports Medicine (2002)

The aim of this work was to study the posturokinetic capacities and use of visual information by judoists according to their level of competition. Twenty male judoists aged between 16 and 19 took part. They were separated into two groups: those that competed at regional level and those that competed at national and international level. Static balance was measured on a force platform. No difference was seen between the two groups. However, it seems that visual information is more important to the higher level judoists. Perhaps the level of competition influences the sensory canals involved in balance.
IL-2–dependent adaptive control of NK cell homeostasis
Authors: Georg Gasteiger, Saskia Hemmers, Paula D. Bos, Joseph C. Sun, Alexander Y. Rudensky
Journal: The Journal of Experimental Medicine (2013)

Activation and expansion of T and B lymphocytes and myeloid cells are controlled by Foxp3+ regulatory T cells (T reg cells), and their deficiency results in a fatal lympho- and myeloproliferative syndrome. A role for T reg cells in the homeostasis of innate lymphocyte lineages remained unknown. Here, we report that T reg cells restrained the expansion of immature CD127+ NK cells, which had the unique ability to up-regulate the IL2Rα (CD25) in response to the proinflammatory cytokine IL-12. In addition, we observed the preferential accumulation of CD127+ NK cells in mice bearing progressing tumors or suffering from chronic viral infection. CD127+ NK cells expanded in an IL-2–dependent manner upon T reg cell depletion and were able to give rise to mature NK cells, indicating that the latter can develop through a CD25+ intermediate stage. Thus, T reg cells restrain the IL-2–dependent CD4+ T cell help for CD127+ immature NK cells. These findings highlight the adaptive control of innate lymphocyte homeostasis.
Signal transducer and activator of transcription (STAT)-3 regulates microRNA gene expression in chronic lymphocytic leukemia cells
Authors: Uri Rozovski, George A Calin, Tetsuro Setoyama, Lucilla D’Abundo, David M Harris, Ping Li, Zhiming Liu, Srdana Grgurevic, Alessandra Ferrajoli, Stefan Faderl, Jan A Burger, Susan O’Brien, William G Wierda, Michael J Keating, Zeev Estrov
Journal: Molecular Cancer (2013)

Abstract Backgrounds Approximately 1,000 microRNAs (miRs) are present in the human genome; however, little is known about the regulation of miR transcription. Because miR levels are deregulated in chronic lymphocytic leukemia (CLL) and signal transducer and activator of transcription (STAT)-3 is constitutively activated in CLL, we sought to determine whether STAT3 affects the transcription of miR genes in CLL cells. Methods We used publically available data from the ENCODE project to identify putative STAT3 binding sites in the promoters of miR genes. Then we transfected CLL cells with STAT3-shRNA or with an empty vector, and to determine which miRs are differentially expressed, we used a miR microarray approach followed by validation of the microarray results for 6 miRs using quantitative real-time polymerase chain reaction (qRT-PCR). Results We identified putative STAT3 binding sites in 160 promoter regions of 200 miRs, including miR-21, miR-29, and miR-155, whose levels have been reported to be upregulated in CLL. Levels of 72 miRs were downregulated (n = 63) or upregulated (n = 9). qRT-PCR confirmed the array data in 5 of 6 miRs. Conclusions The presence of activated STAT3 has a profound effect on miR expression in CLL cells.
SIRT1 regulates oncogenesis via a mutant p53-dependent pathway in hepatocellular carcinoma
Authors: Zheng Yun Zhang, Doopyo Hong, Seung Hoon Nam, Jong Man Kim, Yong Han Paik, Jae Won Joh, Choon Hyuck David Kwon, Jae Berm Park, Gyu-Seong Choi, Kyu Yun Jang, Cheol Keun Park, Sung Joo Kim
Journal: Journal of Hepatology (2014)
Elevated autocrine EDIL3 protects hepatocellular carcinoma from anoikis through RGD-mediated integrin activation
Authors: Ming-Xuan Feng, Ming-Ze Ma, Ying Fu, Jun Li, Tao Wang, Feng Xue, Jian-Jun Zhang, Wen-Xin Qin, Jian-Ren Gu, Zhi-Gang Zhang, Qiang Xia
Journal: Molecular Cancer (2014)

A remolded microenvironment in hepatocellular carcinoma (HCC) caused by abnormally expressed matricellular proteins could promote HCC progression. The cell-matrix interactions mediated by integrins play an important role in tumor microenvironment. Epidermal Growth Factor-like repeats and Discoidin I-Like Domains 3 (EDIL3), an extracellular matrix (ECM) protein with angiogenic and anti-inflammatory effects, is abnormally highly expressed in HCC. Here we aim to analyze its expression in liver and HCC tissues, investigate the underlined mechanisms accounted for HCC progression.EDIL3 expression level is examined in normal liver, cirrhotic liver and HCC at both mRNA and protein level. The association between EDIL3 and clinical outcomes is analyzed. The pattern of EDIL3 expression and location is examined using Immunofluorescence and ELISA. Overexpression or knock-down of EDIL3 in a panel of cell lines are subjected to assays related to proliferation, invasion, and anoikis to investigate the mechanisms of this matrix protein in HCC progression. Recombinant EDIL3 treatment is applied to confirm the results.Compared with normal liver and cirrhotic liver, EDIL3 is elevated in HCC. High level of EDIL3 protein is much more commonly in patients with larger tumor or portal vein tumor thrombus (PVTT) formation, associated with poor prognosis. EDIL3 is abundantly expressed in HCC cells and secreted by cancer cells. In vitro and in vivo studies indicate that EDIL3, probably in an autocrine manner, inhibits anoikis and promotes anchorage-independent growth of HCC cells. Further mechanistic studies suggest integrin ligation by EDIL3 and thus that the sustained activation of the FAK-Src-AKT signal is responsible for the anoikis resistance and anchorage independence. Both the administration of cilengitide, a RGD-containing integrin antagonist, and silencing of integrin αV, an important RGD-binding integrin, results in the blockade of anoikis-resistance induced by EDIL3.Our study suggests that high levels of autocrine EDIL3 may contribute to a receptive microenvironment for the survival of detached HCC cells and may involve in cancer cell spreading. We also highlight the importance of interaction between EDIL3 and integrin αV and suggest disrupting the ligation of EDIL3 to integrins via RGD-blocking in selected patients may bear potential therapeutic value.
Enhanced Levels of Soluble and Membrane-Bound CD40 Ligand in Patients With Unstable Angina
Authors: Pål Aukrust, Fredrik Müller, Thor Ueland, Trude Berget, Elinor Aaser, Anne Brunsvig, Nils Olav Solum, Kolbjørn Forfang, Stig S. Frøland, Lars Gullestad
Journal: Circulation (1999)

Background —The CD40 ligand (CD40L) on activated T cells and platelets may be activating matrix metalloproteinases, inducing procoagulant activity, and be involved in the pathogenesis of acute coronary syndromes by promoting plaque rupture in atheroma. Methods and Results —To study the role of CD40L-CD40 interaction in coronary disease, we analyzed levels of soluble (s) and membrane-bound CD40L in the peripheral blood from 29 patients with stable angina, 26 with unstable angina, and 19 controls. Our main findings follow. (1) Patients with unstable angina had significantly raised serum levels of sCD40L when compared with patients with stable angina and controls. (2) Platelets could release large amounts of sCD40L when stimulated ex vivo with the thrombin receptor–agonist peptide SFLLRN in both patients and controls. (3) Platelets in patients with unstable angina were characterized ex vivo by decreased intracellular levels and decreased SFLLRN-stimulated release of sCD40L, which may possibly represent a higher percentage of degranulated platelets in these patients. (4) T cells in patients with unstable angina had enhanced surface expression of CD40L and increased release of sCD40L on anti-CD3/anti-CD28 stimulation in vitro when compared with patients with stable angina and controls. (5) Recombinant CD40L and serum from patients with unstable angina who had high sCD40L levels induced enhanced release of monocyte chemoattractant peptide-1 from mononuclear cells, a CC-chemokine involved in the pathogenesis of atherosclerosis. Conclusions —This first demonstration of enhanced levels of soluble and membrane-bound forms of CD40L in angina patients, with particularly high levels in patients with unstable angina, suggests that CD40L-CD40 interaction may play a pathogenic role in both the long-term atherosclerotic process and in the triggering and propagation of acute coronary syndromes.
The role of potassium in the metabolic control of coronary vascular resistance of the dog.
Authors: P A Murray, F L Belloni, H V Sparks
Journal: Circulation Research (1979)

We tested the hypothesis that potassium ion (K+) is involved in the local control of the coronary circulation. The left coronary artery was perfused at constant flow in closed-chest, anesthetized dogs. Step increases in heart rate caused transient (six dogs) or sustained (three dogs) increases in coronary sinus plasma [K+] averaging 0.53 mEq/liter. When the effects of vascular transit delay were accounted for, we found that [K+] changes preceded the vasodilation seen with increased heart rate. We used a mathematical model to calculate changes in interstitial [K+] from arterial and venous [K+] and K+ release rate. The magnitude of the changes in interstitial [K+] appeared to be sufficient to account for a considerable portion but not all of the initial changes in coronary vascular resistance associated with increased heart rate. Thus potassium seems to be involved at least transiently, and, in three of nine dogs, for a more sustained period, in heart rate-induced coronary vasodilation. Cessations (for 15 seconds) of coronary blood flow resulted in transient postischemic increases of coronary sinus [K+] averaging 0.55 mEq/liter. In this case, correction for vascular transit disclosed that the recovery of [K+] preceded the return of vascular tone to baseline for only the second half of the recovery, implying only a limited role for potassium in this response. Potassium appears to play a significant but transient role in the local control of the coronary circulation.
A Prospective, Randomized Comparison of the Metabolic Effects of Pioglitazone or Rosiglitazone in Patients With Type 2 Diabetes Who Were Previously Treated With Troglitazone
Authors: Mehmood A. Khan, John V. St. Peter, Jay L. Xue
Journal: Diabetes Care (2002)

OBJECTIVE—To characterize potential differences in glycemic control, plasma lipid level, and weight in a cohort of patients previously treated with troglitazone (TROG) who were switched to either pioglitazone or rosiglitazone. RESEARCH DESIGN AND METHODS—After a 2-week washout from TROG, 186 patients were randomly assigned to receive either pioglitazone (PIO) or rosiglitazone (ROSI). Weight, HbA1c, and fasting lipid profile were documented before discontinuing TROG and at 4 months after starting either pioglitazone or rosiglitazone. Secondarily, the effect of concurrent medications on study outcomes was assessed. RESULTS—A total of 127 patients completed follow-up: 67 individuals in the PIO group (32 women, 35 men) and 60 individuals in the ROSI group (33 women, 27 men). There were no significant differences in gender mix, age, weight, fasting lipid profile, or HbA1c between the ROSI and PIO groups. After 4 months of randomized treatment, no change in HbA1c from baseline between or within groups was noted. Both groups experienced an equal and significant increase in weight from baseline of ∼2.0 kg. Thiazolidinedione and HMG-CoA reductase inhibitor therapy had significant and independent effects on lipid profile (P &amp;lt; 0.005). Significant improvements in lipid profile were noted in the PIO group (P &amp;lt; 0.01), whereas none were detected with conversion to ROSI. Specifically, the PIO group experienced an average decrease in total cholesterol of ∼20 mg/dl. CONCLUSIONS—Differing effects on lipid profile were apparent after random conversion from TROG to either PIO or ROSI, despite similar weight increase and glycemic control. The clinical significance of these differences remains to be determined, and further comparative research is warranted.
Affinity-Tuned ErbB2 or EGFR Chimeric Antigen Receptor T Cells Exhibit an Increased Therapeutic Index against Tumors in Mice
Authors: Xiaojun Liu, Shuguang Jiang, Chongyun Fang, Shiyu Yang, Devvora Olalere, Edward C. Pequignot, Alexandria P. Cogdill, Na Li, Melissa Ramones, Brian Granda, Li Zhou, Andreas Loew, Regina M. Young, Carl H. June, Yangbing Zhao
Journal: Cancer Research (2015)

Target-mediated toxicity is a major limitation in the development of chimeric antigen T-cell receptors (CAR) for adoptive cell therapy of solid tumors. In this study, we developed a strategy to adjust the affinities of the scFv component of CAR to discriminate tumors overexpressing the target from normal tissues that express it at physiologic levels. A CAR-expressing T-cell panel was generated with target antigen affinities varying over three orders of magnitude. High-affinity cells recognized target expressed at any level, including at levels in normal cells that were undetectable by flow cytometry. Affinity-tuned cells exhibited robust antitumor efficacy similar to high-affinity cells, but spared normal cells expressing physiologic target levels. The use of affinity-tuned scFvs offers a strategy to empower wider use of CAR T cells against validated targets widely overexpressed on solid tumors, including those considered undruggable by this approach.
Gastric emptying in patients with fundal gastritis and gastric cancer.
Authors: M Tatsuta, H Iishi, S Okuda
Journal: Gut (1990)

Gastric emptying was compared in patients with gastric cancers and fundal gastritis to determine its value in identifying patients at high risk of gastric cancer. Gastric emptying was measured by the acetaminophen absorption method, and the extent of fundal gastritis was determined by the endoscopic Congo red test. The results showed that gastric emptying was significantly slower in patients with severe fundal gastritis than in those without. Gastric emptying in patients with differentiated adenocarcinomas was significantly slower than in those with undifferentiated adenocarcinoma, its value being similar to that in patients with severe fundal gastritis. The Congo red test showed that the incidence of severe fundal gastritis was significantly greater in patients with differentiated adenocarcinomas than in those with undifferentiated cancers. These findings suggest that delayed gastric emptying may allow prolonged contact between dietary carcinogens and the stomach.
Microscopic colitis: a common diarrhoeal disease. An epidemiological study in Orebro, Sweden, 1993-1998
Authors: M Olesen
Journal: Gut (2004)

Microscopic colitis, including collagenous colitis and lymphocytic colitis, mainly affects middle aged and older subjects, with a female predominance in collagenous colitis. The diseases have previously been regarded as rare. We present an epidemiological study of microscopic colitis in a well defined Swedish population.Patients were retrospectively searched for in colonoscopy reports of those who had a colonoscopy in the period 1993-1998 for non-bloody diarrhoea. All colonic mucosal biopsies were reassessed using strict diagnostic criteria.Biopsies from 1018 patients were reassessed. Fifty one (45 female) collagenous colitis patients and 46 (31 female) lymphocytic colitis patients were diagnosed. Median age at diagnosis was 64 years in collagenous colitis and 59 years in lymphocytic colitis. The mean annual incidence of collagenous colitis was 4.9/10(5) inhabitants (95% confidence interval (CI) 3.6-6.2/10(5)) and of lymphocytic colitis 4.4/10(5) inhabitants (95% CI 3.1-5.7/10(5)). The annual incidence of collagenous colitis increased from 3.7/10(5) in 1993-1995 to 6.1/10(5) in 1996-1998 (difference 2.4/10(5) (95% CI -0.3-5.1/10(5))) whereas the incidence of lymphocytic colitis increased from 3.1/10(5) to 5.7/10(5) (difference 2.6/10(5) (95% CI 0.1-5.2/10(5))).The annual incidences of collagenous colitis and lymphocytic colitis are higher than considered previously and are now equal to the incidence of Crohn's disease in Sweden, and combined rates approach the incidence of ulcerative colitis. Microscopic colitis was diagnosed in 10% of all patients with non-bloody diarrhoea referred for colonoscopy and in almost 20% of those older than 70 years.
Synthesis and biodistribution of immunoconjugates of a human IgM and polymeric drug carriers
Authors: C.J.T. Hoes, J. Grootoonk, J. Feijen, P.J. Boon, F. Kaspersen, P. Loeffen, I. Schlachter, M. Winters, E.S. Bos
Journal: Journal of Controlled Release (1992)
Penile ulceration in fatal malignant atrophic papulosis (Degos’ disease)
Authors: K.F. Thomson, A.S. Highet
Journal: British Journal of Dermatology (2000)

Journal Article Penile ulceration in fatal malignant atrophic papulosis (Degos' disease) Get access K.F. Thomson, K.F. Thomson Department of Dermatology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K. *York District Hospital, Wigginton Road, York YO31 8HE, U.K.E‐mail: kfthomson@aol.com Search for other works by this author on: Oxford Academic Google Scholar A.S. Highet A.S. Highet Department of Dermatology, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, U.K. *York District Hospital, Wigginton Road, York YO31 8HE, U.K.E‐mail: kfthomson@aol.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 143, Issue 6, 1 December 2000, Pages 1320–1322, https://doi.org/10.1046/j.1365-2133.2000.03911.x Published: 01 December 2000
From Mouse to Whale
Authors: Sami F. Noujaim, Elena Lucca, Viviana Muñoz, Dharmendra Persaud, Omer Berenfeld, Frits L. Meijler, José Jalife
Journal: Circulation (2004)

On the ECG, the PR interval measures the time taken by an electrical impulse generated in the sinoatrial node to propagate from atria to ventricles. From mouse to whale, the PR interval increases approximately 10(1), whereas body mass (BM) augments approximately 10(6). Scaling of many biological processes (eg, metabolic rate, life span, aortic diameter) is described by the allometric equation Y=Y(0) x BM(b), where Y is the biological process and b is the scaling exponent that is an integer multiple of 1/4. Hierarchical branching networks have been proposed to be the underlying mechanism for the 1/4 power allometric law.We first derived analytically the allometric equation for the PR interval. We assumed that the heart behaves as a set of "fractal-like" networks that tend to minimize propagation time across the conducting system while ensuring a hemodynamically optimal atrioventricular activation sequence. Our derivation yielded the relationship PR proportional, variant BM1/4. We subsequently obtained previously published values of PR interval, heart rate, and BM of 541 mammals representing 33 species. Double-logarithmic analysis demonstrates that PR interval increases as heart rate decreases, and both variables relate to BM following the 1/4 power law. Most important, the best fit for PR versus BM is described by the equation PR=53 x BM0.24. Hence, the empirically determined exponent (0.24) is close to 1/4, as predicted.We have demonstrated that the PR interval of mammals scales as the 1/4 power of the BM, following the universal law for allometric scaling to ensure an optimal atrioventricular activation sequence.
Jones’ Clinical Paediatric Surgery: Diagnosis and Management
Authors: R. Lawrence Moss
Journal: JAMA (2009)

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