tbuckley/cabot-search huggingface dataset:
Low ileal interleukin 10 concentrations are predictive of endoscopic recurrence in patients with Crohn's disease
Authors: B Meresse
Journal: Gut (2002)

Background: Endoscopic recurrence after surgery in Crohn9s disease is frequent and unpredictable. Abnormal intestinal production of pro- (interleukin (IL)-1β, tumour necrosis factor α (TNF-α)) and anti- (IL-10) inflammatory cytokines has been associated with severe outcome in experimental models of colitis. Patients and methods: We evaluated if ileal TNF-α, IL-1β, or IL-10 mRNA levels measured at the time of surgery predict endoscopic recurrence, and if ileal IL-10 levels are associated with particular IL-10 promoter alleles. Ileal biopsies were obtained peroperatively from the healthy neoileum of patients undergoing a right ileocolectomy for Crohn9s disease. Mucosal TNF-α, IL-1β, and IL-10 mRNA levels were quantified by competitive polymerase chain reaction. A cut off value was determined using a receiver operating curve. IL-10.G promoter haplotypes were analysed using a polymorphic dinucleotide repeat in the IL-10 promoter region. Results: Three months after surgery, 53% of patients had endoscopic recurrence while 47% remained free of disease. The risk of endoscopic recurrence correlated with ileal IL-10 mRNA concentrations (<i>r</i><sup>2</sup>=0.81). Endoscopic recurrence occurred more frequently in patients classified as low IL-10 producers than in those that were high producers (80% <i>v</i> 40%) (p=0.02). Patients with at least one of the two alleles G7–8 or G10–13 produced, respectively, higher (p=0.006) and lower (p=0.029) ileal IL-10 mRNA. The distribution of IL-10.G microsatellite genotypes was similar in patients with or without endoscopic recurrence. Conclusion: Low ileal IL-10 mRNA concentration is a good marker of endoscopic recurrence in Crohn9s disease but the distribution of IL-10.G haplotypes cannot predict the postoperative evolution of the disease.
Novel Embryonic Genes Are Preferentially Expressed by Autonomously Replicating Rat Embryonic and Neointimal Smooth Muscle Cells
Authors: Mary C. M. Weiser-Evans, Philip E. Schwartz, Nicole A. Grieshaber, Bryan E. Quinn, Scott S. Grieshaber, James K. Belknap, Peter M. Mourani, Richard A. Majack, Kurt R. Stenmark
Journal: Circulation Research (2000)

Abstract —We sought to identify and characterize the expression pattern of genes expressed by smooth muscle cells (SMCs) during periods of self-driven replication during vascular development and after vascular injury. Primary screening of a rat embryonic aortic SMC–specific cDNA library was accomplished with an autonomous embryonic SMC–enriched, nonautonomous adult SMC–subtracted cDNA probe. Positive clones were rescreened in parallel with embryonic SMC–specific and adult SMC–specific cDNA probes. We identified 14 clones that hybridized only with the embryonic cDNA (“emb” clones), 11 of which did not share significant homology with sequences in any of the databases. Five of these novel emb genes (emb7, emb8, emb20, emb37, and emb41) were selectively and only transiently reexpressed in vivo by neointimal SMCs during periods of rapid replication. The emb8:embryonic growth–associated protein (EGAP), which was studied the most extensively, was expressed at high levels by cultured, autonomously replicating embryonic and neointimal SMCs but was detected only at low levels even in mitogenically stimulated adult SMCs. Finally, the administration of antisense EGAP oligonucleotides markedly attenuated embryonic and neointimal SMC replication rates. We suggest that autonomous replication of SMCs may be essential for normal vascular morphogenesis and for the vascular response to injury and that these newly identified “embryonic” genes may be part of the molecular machinery that drives this unique growth phenotype.
Levels of Hypoxia-Inducible Factor-1 During Breast Carcinogenesis
Authors: R. Bos, H. Zhong, C. F. Hanrahan, E. C. M. Mommers, G. L. Semenza, H. M. Pinedo, M. D. Abeloff, J. W. Simons, P. J. van Diest, E. van der Wall
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates gene expression in critical pathways involved in tumor growth and metastases. In this report, we investigated whether the level of HIF-1α is increased during carcinogenesis in breast tissue and is associated with other tumor biomarkers. Methods: Paraffin-embedded clinical specimens from five pathologic stages of breast tumorigenesis and from normal breast tissue were used. HIF-1α protein and the biomarkers vascular endothelial growth factor (VEGF), HER-2/neu, p53, Ki-67, and estrogen receptor (ER) were identified immunohistochemically, and microvessel density (a measure of angiogenesis) was determined. Associations among levels of HIF-1α and these biomarkers were tested statistically. All statistical tests are two-sided. Results: The frequency of HIF-1α-positive cells in a specimen increased with the specimen's pathologic stage (P<.001, χ2 test for trend) as follows: normal breast tissue (0 specimens with ≥1% HIF-1α-positive cells in 10 specimens tested), ductal hyperplastic lesions (0 in 10), well-differentiated ductal carcinomas in situ (DCIS) (11 in 20), well-differentiated invasive breast cancers (12 in 20), poorly differentiated DCIS (17 in 20), and poorly differentiated invasive carcinomas (20 in 20). Increased levels of HIF-1α were statistically significantly associated with high proliferation and increased expression of VEGF and ER proteins. In DCIS lesions, increased levels of HIF-1α were statistically significantly associated with increased microvessel density. HIF-1α showed a borderline association with HER-2/neu but no association with p53. Conclusions: The level of HIF-1α increases as the pathologic stage increases and is higher in poorly differentiated lesions than in the corresponding type of well-differentiated lesions. Increased levels of HIF-1α are associated with increased proliferation and increased expression of ER and VEGF. Thus, increased levels of HIF-1α are potentially associated with more aggressive tumors.
Angiogenesis inhibition suppresses collagen arthritis.
Authors: D J Peacock, M L Banquerigo, E Brahn
Journal: The Journal of Experimental Medicine (1992)

Neovascularization is observed in a spectrum of diseases such as solid tumors, diabetic retinopathy, and rheumatoid arthritis. It is also evident in rat collage-induced arthritis (CIA), an animal model with histologic, clinical, and radiographic manifestations resembling rheumatoid arthritis. To evaluate the effects of angioinhibition in CIA, Louvain rats were immunized with type II collagen to induce arthritis and then administered an angiogenesis inhibitor, AGM-1470, in an attempt to either prevent arthritis or suppress established disease. Using clinical and radiographic criteria, AGM-1470 prevented CIA and significantly suppressed established disease without evidence of immunosuppression. Histologic sections from control ankle joints manifested pannus and neovascularization, which were absent in experimental animals. This is the first study to investigate this novel agent in an autoimmune disease, and additional evaluation of this promising compound in other diseases that are potentially angiogenesis dependent, such as rheumatoid arthritis, might be warranted.
Cytomegalovirus Infection With Interleukin-6 Response Predicts Cardiac Mortality in Patients With Coronary Artery Disease
Authors: Stefan Blankenberg, Hans J. Rupprecht, Christoph Bickel, Christine Espinola-Klein, Gerd Rippin, Gerd Hafner, Manfred Ossendorf, Katja Steinhagen, Jürgen Meyer
Journal: Circulation (2001)

Background —Prospective data relating previous exposure to cytomegalovirus (CMV) to the risk of cardiac mortality are controversial. We investigated the effect of previous exposure to CMV infection on the risk of future cardiac disease–related death in relation to an underlying inflammatory response. Methods and Results —Coronary angiography was performed in 1134 subjects, and 989 patients with documented coronary artery disease were studied prospectively. CMV-IgG titers and interleukin (IL)-6 levels were measured before angiography. Increasing titers of CMV correlated with the elevation of IL-6 levels ( P &lt;0.001) after adjustment for possible confounders. All patients were followed up for a median of 3.1 years (maximum 4.3 years). During follow-up, 96 patients died, 70 of cardiac disease. Overall, CMV seropositivity was not related to cardiac mortality after adjustment for confounding variables ( P =0.19). In contrast, in patients with elevated IL-6 levels (≥11.9 pg/mL, median level), CMV seropositivity was independently associated with a 3.2-fold (95% CI 1.4 to 7.3, P =0.007) increase in risk of future cardiac death, whereas in individuals without IL-6 elevation, previous CMV infection had no effect on cardiac mortality. Conclusions —CMV seropositivity in patients with an inflammatory response is independently associated with future cardiac mortality, whereas this association is lost in patients who do not demonstrate an inflammatory response. These data support the hypothesis that the atherosclerotic effects of CMV are mediated through an underlying inflammatory response.
Specific Recruitment of Antigen-presenting Cells by Chemerin, a Novel Processed Ligand from Human Inflammatory Fluids
Authors: Valérie Wittamer, Jean-Denis Franssen, Marisa Vulcano, Jean-François Mirjolet, Emmanuel Le Poul, Isabelle Migeotte, Stéphane Brézillon, Richard Tyldesley, Cédric Blanpain, Michel Detheux, Alberto Mantovani, Silvano Sozzani, Gilbert Vassart, Marc Parmentier, David Communi
Journal: The Journal of Experimental Medicine (2003)

Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein-coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42-p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.
Localized doxorubicin chemotherapy with a biopolymeric nanocarrier improves survival and reduces toxicity in xenografts of human breast cancer
Authors: Shuang Cai, Sharadvi Thati, Taryn R. Bagby, Hassam-Mustafa Diab, Neal M. Davies, Mark S. Cohen, M. Laird Forrest
Journal: Journal of Controlled Release (2010)
THE INFLUENCE OF VISUAL AND AUDITORY STIMULI ON THE ELECTROENCEPHALOGRAPHIC TRACING OF PETIT MAL
Authors: ROBERT S. SCHWAB
Journal: American Journal of Psychiatry (1941)

1. Light stimuli affect the alpha rhythm according to the "all or none" law. 2. Light stimuli have a delayed reaction time in short petit-mal attacks. 3. Light stimuli are not perceived in long petit-mal attacks. 4. Both light and sound stimuli tend to terminate moderately severe petit-mal seizures-the sound being much more effective. 5. When both fail to provoke a response, unconsciousness may be presumed. 6. This method of determining the impairment of consciousness may be useful in: (a) Estimating the severity of petit-mal seizures. (b) The effectiveness of anticonvulsant therapy on the spells.
Address prepared for the Section of Obstetric Medicine
Authors: J. B. Hicks
Journal: BMJ (1873)

More than any man living(y I have a right to take a warm interest, and to which I shall owe till the day of my death a profound loyalty-has made the subject of Public Medicine prominent as one of its Sections.I trust that, great and glorious as the efforts of the profession have been in all ages for the alleviation of suffering and cure of disease, its fature glory will be still greater in the prevention of disease, in elevating the stanidard of lhealtlh, and thereby the happiness and prosperity of all among whom they live.I trust that future history will have to record that it was owing in no small dearee to the efforts of the British Medical Association that this English nation became at last, what it is not now, but what it can be if it so will, a thoroughly healthy people, a people endowed with unalloyed vigour, both of body and mind, who will have ceased tolament an amount of preventable suffering and morta- lity, disgraceful to the civilisation which permits them to exist among us.
AKI in an HIV Patient
Authors: P. Matthew Hartle, Mariu E. Carlo, Jamie P. Dwyer, Agnes B. Fogo
Journal: Journal of the American Society of Nephrology (2013)

The renal manifestations of patients infected with HIV are diverse. Patients may have podocytopathies ranging from a minimal-change-type lesions to FSGS or collapsing glomerulopathy. Furthermore, such patients produce a variety of autoantibodies without clinical signs of the disease. Antiretroviral drugs also cause renal injury, including crystals and tubular injury, acute interstitial nephritis, or mitochondrial toxicity. In these circumstances, it is essential to perform a renal biopsy for diagnosis and to guide treatment. Here we describe a patient with HIV who presented with AKI and hematuria without concomitant systemic manifestations. Renal biopsy elucidated the cause of acute deterioration of kidney function.
A Tissue Engineering Solution for Segmental Defect Regeneration in Load-Bearing Long Bones
Authors: Johannes C. Reichert, Amaia Cipitria, Devakara R. Epari, Siamak Saifzadeh, Pushpanjali Krishnakanth, Arne Berner, Maria A. Woodruff, Hanna Schell, Manav Mehta, Michael A. Schuetz, Georg N. Duda, Dietmar W. Hutmacher
Journal: Science Translational Medicine (2012)

A polycaprolactone-tricalcium phosphate scaffold with recombinant human BMP-7 heals critical-sized bone defects in sheep.
Transport proteins and molecular biology: Is cloning the beginning or the end?
Authors: Decherd Stump, Richard A. Weisiger, Paul D. Berk
Journal: Hepatology (1995)

Long chain fatty acids (LCFAs) are an important energy substrate used by cardiac myocytes and other cells, but the mechanism whereby these molecules cross the plasma membrane is poorly understood. We used an expression cloning strategy and a cDNA library from 3T3-L1 adipocytes to identify a cDNA that, when expressed in cultured cells, augments uptake of LCFAs. This cDNA encodes a novel 646 amino acid fatty acid transport protein (FATP) with six predicted membrane spanning regions and that is integrally associated with membranes. Immunocytochemistry and subcellular fractionation of 3T3-L1 adipocytes show that FATP is localized to the plasma membrane. We propose that FATP is a plasma membrane transporter for LCFAs.
Bile Acid Kinetics in Relation to Sex, Serum Lipids, Body Weights, and Gallbladder Disease in Patients with Various Types of Hyperlipoproteinemia
Authors: Kurt Einarsson, Kjell Hellström, Mora Kallner
Journal: Journal of Clinical Investigation (1974)

Bile acid kinetics were determined in 15 normolipidemic and 61 hyperlipidemic subjects with the aid of [(14)C]cholic acid and [(3)H]chenodeoxycholic acid. The diet was standardized and of natural type. The total bile acid formation was within normal limits in patients with hyperlipoproteinemia types IIa and IIb. On the average the production of cholic acid (C) represented less than 50% of the total bile acid synthesis in both groups. The corresponding value recorded for the controls was 64+/-2% (mean+/-SEM). The synthesis of C in hyperlipoproteinemia type IIa was significantly below normal. Of the 27 patients with the type IV pattern, 18 had a synthesis of C and C + chenodeoxycholic acid (CD) that exceeded the upper range recorded for the controls. In these subjects the C formation represented 73+/-3% of the total bile acid synthesis. Similar findings were also encountered in the five patients with the type V lipoprotein pattern studied. The bile acid pool size of the 11 patients with hyperlipoproteinemia type IV, who had been cholecystectomized or suffered from cholelithiasis, was 900 mg smaller on the average than that of the other subjects with the same type of hyperlipoproteinemia. However, the pool size in the former subjects still tended to be higher than that of the control subjects without evidence of gallbladder "disease". In all groups of subjects the formation of bile acids tended to be higher in the male than in the female subjects. Bile acid synthesis showed no linear correlation to actual body weight, relative body weight, or body surface area. A moderate weight reduction in five patients (one with type IIb and four with type IV pattern) was followed by a 50% reduction of the C and CD synthesis.
Polymerase ζ Activity Is Linked to Replication Timing in Humans: Evidence from Mutational Signatures
Authors: Vladimir B. Seplyarskiy, Georgii A. Bazykin, Ruslan A. Soldatov
Journal: Molecular Biology and Evolution (2015)

Replication timing is an important determinant of germline mutation patterns, with a higher rate of point mutations in late replicating regions. Mechanisms underlying this association remain elusive. One of the suggested explanations is the activity of error-prone DNA polymerases in late-replicating regions. Polymerase zeta (pol ζ), an essential error-prone polymerase biased toward transversions, also has a tendency to produce dinucleotide mutations (DNMs), complex mutational events that simultaneously affect two adjacent nucleotides. Experimental studies have shown that pol ζ is strongly biased toward GC→AA/TT DNMs. Using primate divergence data, we show that the GC→AA/TT pol ζ mutational signature is the most frequent among DNMs, and its rate exceeds the mean rate of other DNM types by a factor of approximately 10. Unlike the overall rate of DNMs, the pol ζ signature drastically increases with the replication time in the human genome. Finally, the pol ζ signature is enriched in transcribed regions, and there is a strong prevalence of GC→TT over GC→AA DNMs on the nontemplate strand, indicating association with transcription. A recurrently occurring GC→TT DNM in HRAS and SOD1 genes causes the Costello syndrome and amyotrophic lateral sclerosis correspondently; we observe an approximately 1 kb long mutation hotspot enriched by transversions near these DNMs in both cases, suggesting a link between these diseases and pol ζ activity. This study uncovers the genomic preferences of pol ζ, shedding light on a novel cause of mutational heterogeneity along the genome.
1038 MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) ACTS AS AN ANTI-FIBROTIC CYTOKINE IN EXPERIMENTAL LIVER FIBROSIS VIA CD74 AND AMPK
Authors: P. Heinrichs, M. Jung, C. Offermanns, M.-L. Berres, A. Nellen, P. Schmitz, L. Leng, R. Bucala, C. Trautwein, C. Weber, J. Bernhagen, H.E. Wasmuth
Journal: Journal of Hepatology (2011)
Effects of Tezosentan on Symptoms and Clinical Outcomes in Patients With Acute Heart Failure
Authors: John J. V. McMurray, John R. Teerlink, Gadi Cotter, Robert C. Bourge, John G. F. Cleland, Guillaume Jondeau, Henry Krum, Marco Metra, Christopher M. O’Connor, John D. Parker, Guillermo Torre-Amione, Dirk J. van Veldhuisen, Jim Lewsey, Aline Frey, Maurizio Rainisio, Isaac Kobrin, for the VERITAS Investigators
Journal: JAMA (2007)

Plasma concentrations of the vasoconstrictor peptide endothelin-1 are increased in patients with heart failure, and higher concentrations are associated with worse outcomes. Tezosentan is an intravenous short-acting endothelin receptor antagonist that has favorable hemodynamic actions in heart failure.To determine if tezosentan improves outcomes in patients with acute heart failure.The Value of Endothelin Receptor Inhibition With Tezosentan in Acute Heart Failure Studies, 2 independent, identical, and concurrent randomized, double-blind, placebo-controlled, parallel-group trials conducted from April 2003 through January 2005 at sites in Australia, Europe, Israel, and North America. Patients admitted within the previous 24 hours with persisting dyspnea and a respiratory rate of 24/min or greater were eligible provided they fulfilled 2 of 4 criteria: (1) elevated plasma concentrations of B-type or N-terminal pro-B-type natriuretic peptide, (2) clinical pulmonary edema, (3) radiologic pulmonary congestion or edema, or (4) left ventricular systolic dysfunction.Infusion of tezosentan (5 mg/h for 30 minutes, followed by 1 mg/h for 24 to 72 hours [n = 730]) or placebo (n = 718).The coprimary end points were change in dyspnea (measured at 3, 6, and 24 hours using a visual analog scale from 0-100) over 24 hours (as area under the curve) in the individual trials and incidence of death or worsening heart failure at 7 days in both trials combined.Of the 1435 patients who received treatment as assigned, 855 (60%) were men; mean age was 70 years. Mean left ventricular ejection fraction (measured in 779 patients [54%]) was 29% (SD, 11%). Baseline dyspnea scores were similar in the 2 treatment groups. Tezosentan did not improve dyspnea more than placebo in either trial, with a mean treatment difference of -12 (95% confidence interval [CI], -105 to 81) mm . h (P = .80) in the first trial and -25 (95% CI, -119 to 69) mm x h (P = .60) in the second. The incidence of death or worsening heart failure at 7 days in the combined trials was 26% in each treatment group (odds ratio, 0.99; 95% confidence interval, 0.82-1.21; P = .95).The endothelin receptor antagonist tezosentan did not improve symptoms or clinical outcomes in patients with acute heart failure.clinicaltrials.gov Identifiers: NCT00525707 (VERITAS-1) and NCT00524433 (VERITAS-2).
Effects of in-vivo and in-vitro environments on the metabolism of the cumulus-oocyte complex and its influence on oocyte developmental capacity
Authors: M L Sutton, R B Gilchrist, J G Thompson
Journal: Human Reproduction Update (2003)

There has been an improvement in the blastocyst rates achieved following in-vitro embryo production that can largely be attributed to improved embryo culture conditions based on an increased knowledge of the in-vivo environment, as well as the metabolic needs of the embryo. Despite this, in-vitro oocyte maturation (IVM) conditions have remained largely unchanged. Within the antral follicle, numerous events affect oocyte maturation and the acquisition of developmental competency, including: interactions between somatic cells of the follicle (in particular cumulus cells) and the oocyte; the composition of follicular fluid; and the temperature and vascularity of the follicular environment. Many of these factors change with follicle size and oocyte growth. In contrast, culture conditions for IVM are based on somatic cells that often do not reflect the follicular environment, and/or have complex compositions or additives such as macromolecule supplements that are undefined in nature. Metabolites included in media such as glucose, pyruvate, oxygen and amino acids have been shown to have differential influences on oocyte maturation and competency. Manipulation of these factors and application of gained knowledge of the in-vivo environment may result in improved in-vitro oocyte maturation and overall in-vitro embryo production.