tbuckley/cabot-search huggingface dataset:
Roles of Kruppel-like factor 4 in oesophageal epithelial cells in Barrett's epithelium development
Authors: H. Kazumori, S. Ishihara, Y. Takahashi, Y. Amano, Y. Kinoshita
Journal: Gut (2010)

<h3>Objectives</h3> The mechanism of transformation to intestinal metaplasia in Barrett9s oesophagus has not been clarified. We previously reported that bile acids activate the Cdx2 promoter via nuclear factor kappa B (NF-κB) and stimulate production of Cdx2 protein in oesophageal keratinocytes, resulting in production of intestinal-type mucin. Krüppel-like factor 4 (KLF4) is an important transcription factor in the development of intestinal mucosa and has similar functions as Cdx2. In the present study, we investigated the direct effects of bile acids on KLF4 expression as well as the precise mechanisms of expression in cultured oesophageal squamous epithelial cells. <h3>Methods</h3> We investigated the expression of KLF4 in rat and human Barrett9s epithelium specimens, while the response of that expression to bile acids was studied using a KLF4 promoter luciferase assay. In addition, oesophageal squamous epithelial cells were transfected with a KLF4 expression vector, after which their possible transformation into intestinal-type epithelial cells was investigated. <h3>Results</h3> In both rat and human tissues, Barrett9s epithelium strongly expressed KLF4. Furthermore, a bile acids mixture increased KLF4 promoter activity, and mRNA and protein expression in oesophageal epithelial cells. Results from mutation analysis of the KLF4 promoter suggested that the NF-κB binding site is responsible for bile acid-induced activation of the KLF4 promoter. In addition, KLF4 and Cdx2 stimulated each other by directly binding to the promoter of the other, while transfection of the KLF4 expression vector in oesophageal epithelial cells induced production of MUC2 protein. <h3>Conclusion</h3> Bile acid-induced sequential expression of KLF4 followed by MUC2 production may have an important role in the development of Barrett9s epithelium.
New Pharmacological Strategies to Increase cGMP
Authors: Alessia Buglioni, John C. Burnett
Journal: Annual Review of Medicine (2015)

The intracellular nucleotide cyclic guanosine monophosphate (cGMP) is found in many human organ tissues. Its concentration increases in response to the activation of receptor enzymes called guanylyl cyclases (GCs). Different ligands bind GCs, generating the second messenger cGMP, which in turn leads to a variety of biological actions. A deficit or dysfunction of this pathway at the cardiac, vascular, and renal levels manifests in cardiovascular diseases such as heart failure, arterial hypertension, and pulmonary arterial hypertension. An impairment of the cGMP pathway also may be involved in the pathogenesis of obesity as well as dementia. Therefore, agents enhancing the generation of cGMP for the treatment of these conditions have been intensively studied. Some have already been approved, and others are currently under investigation. This review discusses the potential of novel drugs directly or indirectly targeting cGMP as well as the progress of research to date.
Caspase-8 Promotes Cell Motility and Calpain Activity under Nonapoptotic Conditions
Authors: Brooke Helfer, Bernard C. Boswell, Darren Finlay, Angel Cipres, Kristiina Vuori, Tae Bong Kang, David Wallach, Andrea Dorfleutner, Jill M. Lahti, Daniel C. Flynn, Steven M. Frisch
Journal: Cancer Research (2006)

Abstract Significant caspase-8 activity has been found in normal and certain tumor cells, suggesting that caspase-8 possesses an alternative, nonapoptotic function that may contribute to tumor progression. In this article, we report that caspase-8 promotes cell motility. In particular, caspase-8 is required for the optimal activation of calpains, Rac, and lamellipodial assembly. This represents a novel nonapoptotic function of caspase-8 acting at the intersection of the caspase-8 and calpain proteolytic pathways to coordinate cell death versus cell motility signaling. (Cancer Res 2006; 66(8): 4273-8)
Reference values of exhaled nitric oxide in healthy Asian children aged 5 to 18 years
Authors: T-C. Yao, W-I. Lee, L-S. Ou, L-C. Chen, K-W. Yeh, J-L. Huang
Journal: European Respiratory Journal (2011)

This study was undertaken to establish reference values of exhaled nitric oxide fraction ( F eNO ) and its determinants in healthy Asian children. 693 healthy Asian children aged 5–18 yrs were assessed using a single-breath online F eNO measurement (exhaled flow 50 mL·s −1 ), questionnaires, anthropometric measurements, spirometry and total and specific immunoglobulin (Ig) E. Geometric mean F eNO and the upper 95% CI were 13.7 ppb and 49.7 ppb, respectively, for healthy children, and 11.2 ppb and 30.2 ppb, respectively, for those without allergic sensitisation. F eNO was positively associated with age, allergic sensitisation, total IgE, ambient nitric oxide, measurement in the afternoon, and drinking water within 1 h before testing, and was negatively associated with weight. In healthy children without allergic sensitisation, age was the single best explanatory variable. The F eNO predicted values were 1–2 ppb higher in Asian than in Caucasian children in earlier studies, while the upper 95% CI were 9–10 ppb higher. In conclusion, the upper limits of normal F eNO in Asian children depend on age, from 21 ppb in young children to 39 ppb in adolescents. Ethnicity, age, allergic sensitisation, total IgE, ambient nitric oxide, time of testing, drinking water and weight are important determinants.
Vascular transmigration of synovial fibroblasts from patients with rheumatoid arthritis is influenced by extracellular RNA/DNA and the type of endothelial cells
Authors: B. Zimmermann, S. Fischer, S. Lefevre, T. Umscheid, K. Preissner, U. Muller-Ladner, E. Neumann
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Cartilage destruction in joints of patients with rheumatoid arthritis (RA) is driven by synovial fibroblasts (SF). We demonstrated that RASF migrate to distant cartilage within the blood stream in the SCID-mouse model. Previous work showed that extracellular RNA is required for endothelial permeability and lymphocyte transmigration. Influence on RASF transmigration and invasion by intravenous injection of extracellular RNA/DNA and use of different endothelial cells (EC) was analysed. <h3>Material and methods</h3> To determine the adherence of RASF and OASF to EC we used a cell-to-cell binding assays. The RASF transmigration was examined using two-chamber-assays with different EC (HUVEC, HUAEC and primary venous EC). Cartilage was coimplanted with RASF subcutaneously at the ipsilateral side (I) and without RASF at the contralateral side (C) of a SCID mouse. The animals were divided into three groups: Group (1) received 42μg DNase/kg; group (2) received 42 μg RNase/kg; group (3) received saline solution injected intravenous prior to the surgery and every other day. After 45 days the implants were removed and RASF invasion was analysed. <h3>Results</h3> The adherence of RASF to EC monolayers was medium-dependent and increased in comparison to OASF. RASF are able to pass all EC monolayers. In vivo, a significant reduction of cartilage invasion at the ipsilateral side was detectable after treatment with RNase and DNase ((I) control: 2.3±0.7, RNase: 1.2±0.6, p=0.048; DNase: 0.8±0.3, p=0.007). In contrast, contralateral cartilage invasion was not affected ((C) control, 1.3±0.7 vs RNase: 1.2±1.2, p=0.74; DNase: 1.1±0.6, p=0.73). RNase or DNase injection did not inhibit RASF invasion and migration (RNase (I) vs (C): p=0.77; DNase (I) vs (C): p=0.35). <h3>Conclusion</h3> The potential of RASF to attach to and to pass EC monolayers at the arterial and especially the venous side underline the ability for vascular transmigration. The ipsilateral RASF invasion is reduced by intravenous injection of RNase and DNase but the invasion at the contralateral side is unaffected. That showed that the migration of RASF is not inhibited, but the effect of RNase and DNase is higher on non-migrating RASF in contrast to migrating RASF.
Human sperm carbohydrate antigens defined by an antisperm human monoclonal antibody derived from an infertile woman bearing antisperm antibodies in her serum.
Authors: Y Tsuji, H Clausen, E Nudelman, T Kaizu, S Hakomori, S Isojima
Journal: The Journal of Experimental Medicine (1988)

The epitope structure of the human sperm antigen reacting with antibodies present in sera of infertile women has been studied using mAb H6-3C4, which produces immobilization of human sperm in the presence of complement. Another antibody, NUH2, which also induces human sperm immobilization, was used to substantiate the presence of a receptor on sperm involved in susceptibility to immobilization. Both antibodies defined type 2 chain polylactosamine structure. H6-3C4 is directed to internally located repetitive N-acetyllactosamine, i.e., sialyl-i, i, or fucosyl-i. NUH2 defines binary alpha 2----3 sialyl type 2 chain, i.e., sialyl-I. Thus, the presence of antibodies in the sera of infertile women directed to sperm lactosaminoglycan or lactosaminolipid could be the basis for infertility in these cases.
The Silent Crisis
Authors: Julia R. Köhler, Martha Sola-Visner
Journal: JAMA Pediatrics (2013)

"My father went into that house and never came out. Now my mother went into that house. If she doesn't come out, who will take care of me? Will you take care of me?" 4-year-old Jessie asked a woman she had just met that morning, who had accompanied her mother to an office building.
Evidence for genetic anticipation in nodal osteoarthritis
Authors: G. D Wright, M. Regan, C. M Deighton, G. Wallis, M. Doherty
Journal: Annals of the Rheumatic Diseases (1998)

<h3>Objective</h3> Antimicrobial C-type lectin regenerating islet-derived 3 gamma (REG3G) is suppressed in the small intestine during chronic ethanol feeding. Our aim was to determine the mechanism that underlies REG3G suppression during experimental alcoholic liver disease. <h3>Design</h3> Interleukin 22 (IL-22) regulates expression of REG3G. Therefore, we investigated the role of IL-22 in mice subjected to chronic-binge ethanol feeding (NIAAA model). <h3>Results</h3> In a mouse model of alcoholic liver disease, we found that type 3 innate lymphoid cells produce lower levels of IL-22. Reduced IL-22 production was the result of ethanol-induced dysbiosis and lower intestinal levels of indole-3-acetic acid (IAA), a microbiota-derived ligand of the aryl hydrocarbon receptor (AHR), which regulates expression of IL-22. Importantly, faecal levels of IAA were also found to be lower in patients with alcoholic hepatitis compared with healthy controls. Supplementation to restore intestinal levels of IAA protected mice from ethanol-induced steatohepatitis by inducing intestinal expression of IL-22 and REG3G, which prevented translocation of bacteria to liver. We engineered <i>Lactobacillus reuteri</i> to produce IL-22 (<i>L. reuteri</i>/IL-22) and fed them to mice along with the ethanol diet; these mice had reduced liver damage, inflammation and bacterial translocation to the liver compared with mice fed an isogenic control strain and upregulated expression of REG3G in intestine. However, <i>L. reuteri</i>/IL-22 did not reduce ethanol-induced liver disease in <i>Reg3g<sup>–/–</sup></i> mice. <h3>Conclusion</h3> Ethanol-associated dysbiosis reduces levels of IAA and activation of the AHR to decrease expression of IL-22 in the intestine, leading to reduced expression of REG3G; this results in bacterial translocation to the liver and steatohepatitis. Bacteria engineered to produce IL-22 induce expression of REG3G to reduce ethanol-induced steatohepatitis.
A New Method for Estimating Species Age Supports the Coexistence of Malaria Parasites and Their Mammalian Hosts
Authors: Joana C. Silva, Amy Egan, Cesar Arze, John L. Spouge, David G. Harris
Journal: Molecular Biology and Evolution (2015)

Species in the genus Plasmodium cause malaria in humans and infect a variety of mammals and other vertebrates. Currently, estimated ages for several mammalian Plasmodium parasites differ by as much as one order of magnitude, an inaccuracy that frustrates reliable estimation of evolutionary rates of disease-related traits. We developed a novel statistical approach to dating the relative age of evolutionary lineages, based on Total Least Squares regression. We validated this lineage dating approach by applying it to the genus Drosophila. Using data from the Drosophila 12 Genomes project, our approach accurately reconstructs the age of well-established Drosophila clades, including the speciation event that led to the subgenera Drosophila and Sophophora, and age of the melanogaster species subgroup. We applied this approach to hundreds of loci from seven mammalian Plasmodium species. We demonstrate the existence of a molecular clock specific to individual Plasmodium proteins, and estimate the relative age of mammalian-infecting Plasmodium. These analyses indicate that: 1) the split between the human parasite Plasmodium vivax and P. knowlesi, from Old World monkeys, occurred 6.1 times earlier than that between P. falciparum and P. reichenowi, parasites of humans and chimpanzees, respectively; and 2) mammalian Plasmodium parasites originated 22 times earlier than the split between P. falciparum and P. reichenowi. Calibrating the absolute divergence times for Plasmodium with eukaryotic substitution rates, we show that the split between P. falciparum and P. reichenowi occurred 3.0–5.5 Ma, and that mammalian Plasmodium parasites originated over 64 Ma. Our results indicate that mammalian-infecting Plasmodium evolved contemporaneously with their hosts, with little evidence for parasite host-switching on an evolutionary scale, and provide a solid timeframe within which to place the evolution of new Plasmodium species.
Ocular Biomechanics and Biotransport
Authors: C. Ross Ethier, Mark Johnson, Jeff Ruberti
Journal: Annual Review of Biomedical Engineering (2004)

The eye transduces light, and we usually do not think of it as a biomechanical structure. Yet it is actually a pressurized, thick-walled shell that has an internal and external musculature, a remarkably complex internal vascular system, dedicated fluid production and drainage tissues, and a variety of specialized fluid and solute transport systems. Biomechanics is particularly involved in accommodation (focusing near and far), as well as in common disorders such as glaucoma, macular degeneration, myopia, and presbyopia. In this review, we give a (necessarily brief) overview of many of the interesting biomechanical aspects of the eye, concluding with a list of open problems.
Response of plasma prorenin and active renin to chronic and acute alterations of renin secretion in normal humans. Studies using a direct immunoradiometric assay.
Authors: E B Toffelmire, K Slater, P Corvol, J Menard, M Schambelan
Journal: Journal of Clinical Investigation (1989)

We employed a novel immunoradiometric assay to measure plasma levels of active renin and prorenin in physiologic and pharmacologic studies designed to characterize renin biosynthesis and processing in response to both chronic and acute stimuli of renin secretion in normal human subjects. Stimulation of renin secretion with prolonged dietary sodium restriction or amiloride resulted in marked increases in the plasma levels of prorenin, active renin, and plasma renin activity (PRA); suppression of renin secretion with indomethacin resulted in parallel decreases in prorenin, active renin, and PRA. In contrast, acute stimulation with upright activity or administration of an angiotensin-converting enzyme inhibitor, which increased active renin and PRA from 2- to 15-fold, had no effect on prorenin levels. Based on studies in cultured human juxtaglomerular tumor cells, it has been proposed that prorenin is secreted constitutively whereas active renin is stored in and released from secretory granules through a regulated pathway. Our studies are consistent with such a model: the parallel changes in active renin and prorenin with experimental maneuvers of long duration suggest that both the constitutive and regulated pathways are altered under these conditions. The increase in active renin levels in the absence of a change in prorenin that occurs in response to acute stimuli presumably represents the release of preformed active enzyme that is stored in secretory granules.
Insulin acutely decreases hepatic fatty acid synthase activity
Authors: Sonia M. Najjar, Yan Yang, Mats A. Fernström, Sang-Jun Lee, Anthony M. DeAngelis, George A. Abou Rjaily, Qusai Y. Al-Share, Tong Dai, Tiffany A. Miller, Shobha Ratnam, Randall J. Ruch, Stuart Smith, Sue-Hwa Lin, Nicole Beauchemin, Ana Maria Oyarce
Journal: Cell Metabolism (2005)
Impact of Disease Duration on Vascular Surrogates of Early Atherosclerosis in Childhood‐Onset Systemic Lupus Erythematosus
Authors: Julie Barsalou, Timothy J. Bradley, Pascal N. Tyrrell, Cameron Slorach, Lawrence W. K. Ng, Deborah M. Levy, Earl D. Silverman
Journal: Arthritis & Rheumatology (2015)

To determine whether longer disease duration negatively impacts carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and pulse wave velocity (PWV) in a cohort of patients with childhood-onset systemic lupus erythematosus (SLE), and to compare CIMT, FMD, and PWV in patients with childhood-onset SLE with those in healthy children and explore determinants of vascular test results in childhood-onset SLE.Cross-sectional analysis was performed in a prospective longitudinal cohort of patients with childhood-onset SLE at the latest followup visit. Clinical and laboratory data were collected for patients with childhood-onset SLE. CIMT, FMD, and PWV were measured using standardized protocols in patients with childhood-onset SLE and healthy children. Correlations between disease duration and results of the 3 vascular tests were performed. Vascular data in patients with childhood-onset SLE were compared with those in healthy children. Multivariable linear regression was used to identify determinants of CIMT, FMD, and PWV in childhood-onset SLE.Patients with childhood-onset SLE (n = 149) and healthy controls (n = 178) were enrolled. The median age of the patients was 17.2 years (interquartile range [IQR] 15.7-17.9 years), and their median disease duration was 3.2 years (IQR 1.8-4.9 years). The median age of the healthy children was 14.7 years (IQR 13.1-15.9 years). Longer disease duration correlated with worse FMD (r = -0.2, P = 0.031) in patients with childhood-onset SLE. Patients with childhood-onset SLE had smaller (better) CIMT, higher (better) FMD, and similar PWV compared with healthy controls. Linear regression analysis explained <24% of the variation in vascular test results in patients with childhood-onset SLE, suggesting that other variables should be explored as important determinants of CIMT, FMD, and PWV.In this cohort of 149 patients with childhood-onset SLE, patients did not have worse CIMT, FMD, or PWV than did healthy controls. Longer disease duration was associated with worse FMD, suggesting progressive endothelial dysfunction over time.
Effectiveness of an Adjuvant Chemotherapy Regimen for Early-Stage Breast Cancer
Authors: Takeo Fujii, Fanny Le Du, Lianchun Xiao, Takahiro Kogawa, Carlos H. Barcenas, Ricardo H. Alvarez, Vicente Valero, Yu Shen, Naoto T. Ueno
Journal: JAMA Oncology (2015)

Different adjuvant chemotherapy regimens are available for early-stage breast cancer. Because conventional meta-analysis does not allow comparing all regimens, we performed a network meta-analysis to identify the most effective adjuvant chemotherapy regimen.To find the most effective adjuvant therapy regimen for early-stage breast cancer.We searched MEDLINE, Embase, and the Cochrane Library for articles published before June 2015; the American Society of Clinical Oncology annual meeting abstracts from January 1983 through December 2014; and the American Association for Cancer Research annual meeting abstracts from January 1916 through December 2014. Additionally, we manually searched bibliographies for related references.We included randomized clinical trials of adjuvant treatments for early-stage breast cancer that compared 2 or more of the following: no adjuvant chemotherapy; sequential anthracycline-cyclophosphamide and taxane (AC-T); concurrent anthracycline-cyclophosphamide and taxane (ACT); anthracycline-cyclophosphamide without taxane (AC); docetaxel and cyclophosphamide (TC); cyclophosphamide, methotrexate, and fluorouracil (CMF); and platinum-containing regimens.We followed the PRISMA guidelines. Two investigators independently selected the articles and extracted information. Disagreements were resolved by discussion with another author. Quality was assessed by Cochrane risk-of-bias method. Data were pooled using random-effects models.We used network meta-analysis to test the most effective adjuvant therapy regimen in terms of overall survival (OS) by comparing regimens listed in the National Comprehensive Cancer Network guidelines and platinum-containing regimens.We identified 24 trials. The TC and platinum-containing regimens had OS benefit similar to that of sequential AC-T (TC hazard ratio [HR], 0.93; 95% CI, 0.62-1.40; and platinum HR, 0.93; 95% CI, 0.66-1.31). Patients treated with CMF or AC had significantly worse OS than those treated with sequential AC-T (CMF HR, 1.56; 95% CI, 1.32-1.85; and AC HR, 1.22; 95% CI, 1.10-1.37). Platinum-containing regimens tended to be more toxic than sequential AC-T. The toxicity of TC was similar to or less than that of sequential AC-T. Meta-regression analysis showed that hormone receptor status did not impact the HRs for OS for any regimen.Sequential AC-T is likely to be the most effective adjuvant therapy regimen for early-stage breast cancer regardless of hormone receptor status.
Comparison of the antianginal effectiveness of nifedipine, verapamil, and isosorbide dinitrate in patients receiving propranolol: a double-blind study.
Authors: M M Bassan, D Weiler-Ravell, O Shalev
Journal: Circulation (1983)

Ten men with stable angina not fully relieved by optimal doses of propranolol were given on each of four mornings a single dose of 10 mg nifedipine, 120 mg verapamil, isosorbide dinitrate (5 to 30 mg, previously titrated to lower systolic blood pressure by 15 to 20 mm Hg), or placebo, in double-blind fashion. Bicycle exercise to angina was performed hourly for 8 hr thereafter. All three vasodilators increased exercise time by at least 50% by the first hour (p less than .001), with a gradually diminishing effect persisting for 6 to 8 hr (p less than .01). Although for the group there were no differences in magnitude and duration of effect among the three drugs, in five of the individual patients there were important differences in response favoring one or another vasodilator. We conclude that nifedipine, verapamil, and isosorbide dinitrate are equally effective and reasonably long-acting antianginal supplements to propranolol, although some patients may benefit more from one than another of the three.
THE PROGNOSIS IN "ORGANIC BRAIN" SYNDROMES
Authors: SAMUEL B. GUZE, DENNIS P. CANTWELL
Journal: American Journal of Psychiatry (1964)

A study of 117 patients with "organic brain" syndrome seen in consultation over a 4-year period indicated that this syndrome is associated with a poor prognosis. A high mortality rate, frequent subsequent psychiatric hospitalization, and frequent dementia were noted on follow-up. Significant anatomical and chemical abnormalities were found in most of those who died and were autopsied to provide an explanation for the psychiatric illness.