tbuckley/cabot-search huggingface dataset:
Failure of Women’s Hearts
Authors: Mark C. Petrie, Nuala F. Dawson, David R. Murdoch, Andrew P. Davie, John J. V. McMurray
Journal: Circulation (1999)

R ecently, differences in the management of men and women with ischemic heart disease have been highlighted. 1Although at least as great, sex differences in heart failure have received little attention.In this article, we review the evidence that men and women with heart failure may differ with respect to epidemiology, etiology, diagnosis, prognosis, and treatment. EpidemiologyTo date, most studies of the prevalence and incidence of heart failure have identified cases on clinical grounds and, in some instances, with the aid of an ECG and chest radiograph.Thus, the precise type of heart failure (eg, left ventricular systolic dysfunction, or valvular disease) is unclear in most reports.This is important in view of the evidence that left ventricular systolic dysfunction is less common in women than in men with suspected heart failure (see the "Diagnosis" section below). PrevalenceWith these caveats in mind, the major epidemiological surveys of heart failure (see the Figure) [2][3][4][5] show that the overall prevalence rate of heart failure is similar in men and women.This balance, however, reflects a much lower female prevalence Ͻ70 to 75 years of age and a higher prevalence in older women than in older men.Overall, within the population, there appear to be more women than men with heart failure. 6-8a Although age-adjusted rates for both sexes have decreased from 1988 -1995, rates for women have fallen less than those for men.8b IncidenceAlthough the absolute incidence rate is lower than the prevalence rate, the effect of age on sex incidence is similar. 3 EtiologyRisk factors for heart failure appear to differ markedly between the sexes.
Inhibition of inducible nitric oxide synthase protects against liver injury induced by mycobacterial infection and endotoxins
Authors: Reto Guler, Maria L. Olleros, Dominique Vesin, Roumen Parapanov, Christian Vesin, Salomé Kantengwa, Laura Rubbia-Brandt, Noury Mensi, Anne Angelillo-Scherrer, Eduardo Martinez-Soria, Fabienne Tacchini-Cottier, Irene Garcia
Journal: Journal of Hepatology (2004)
Involvement of interleukin-21 in the regulation of colitis-associated colon cancer
Authors: Carmine Stolfi, Angelamaria Rizzo, Eleonora Franzè, Angela Rotondi, Massimo Claudio Fantini, Massimiliano Sarra, Roberta Caruso, Ivan Monteleone, Pierpaolo Sileri, Luana Franceschilli, Flavio Caprioli, Stefano Ferrero, Thomas T. MacDonald, Francesco Pallone, Giovanni Monteleone
Journal: The Journal of Experimental Medicine (2011)

Chronic inflammation is a major driving force in the development of cancer in many tissues, but the array of factors involved in this neoplastic transformation are not well understood. We have investigated the role of interleukin (IL)-21 in colitis-associated colon cancer (CAC), as this cytokine is overexpressed in the gut mucosa of patients with ulcerative colitis (UC), a chronic inflammatory disease associated with colon cancer. IL-21 was increased in the gut of patients with UC-associated colon cancer, and in mice with CAC induced by azoxymethane (AOM) and dextran sulfate sodium (DSS). After AOM+DSS treatment, IL-21 KO mice showed reduced mucosal damage, reduced infiltration of T cells, and diminished production of IL-6 and IL-17A. IL-21–deficient mice also developed fewer and smaller tumors compared with wild-type (WT) mice. Absence of IL-21 reduced signal transducer and activator of transcription 3 activation in tumor and stromal cells. Administration of a neutralizing IL-21 antibody to WT mice after the last DSS cycle decreased the colonic T cell infiltrate and the production of IL-6 and IL-17A and reduced the number of tumors. These observations indicate that IL-21 amplifies an inflammatory milieu that promotes CAC, and suggest that IL-21 blockade may be useful in reducing the risk of UC-associated colon cancer.
Comparison of different methods for enumeration of Langerhans cells in vertical cryosections of human skin
Authors: T. BIEBER, J. RING, O. BRAUN-FALCO
Journal: British Journal of Dermatology (1988)

Journal Article Comparison of different methods for enumeration of Langerhans cells in vertical cryosections of human skin Get access T. BIEBER, T. BIEBER Department of Dermatology, Ludwig‐Maximilian University, Munich, West Germany Dr Thomas Bieber, Department of Dermatology, University of Munich, Frauenlobstrasse 9‐11, D‐8000 Munich 2, West Germany. Search for other works by this author on: Oxford Academic Google Scholar J. RING, J. RING Department of Dermatology, Ludwig‐Maximilian University, Munich, West Germany Search for other works by this author on: Oxford Academic Google Scholar O. BRAUN‐FALCO O. BRAUN‐FALCO Department of Dermatology, Ludwig‐Maximilian University, Munich, West Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 118, Issue 3, 1 March 1988, Pages 385–392, https://doi.org/10.1111/j.1365-2133.1988.tb02432.x Published: 01 March 1988
Heterogeneity in mouse spasmolytic polypeptide-expressing metaplasia lineages identifies markers of metaplastic progression
Authors: Victoria G Weis, Josane F Sousa, Bonnie J LaFleur, Ki Taek Nam, Jared A Weis, Paul E Finke, Nadia A Ameen, James G Fox, James R Goldenring
Journal: Gut (2012)

Spasmolytic polypeptide-expressing metaplasia (SPEM) develops as a preneoplastic lesion in the stomachs of mice and humans after parietal cell loss. To identify the commonalities and differences between phenotypic SPEM lineages, SPEM were studied from three different mouse models of parietal cell loss: with chronic inflammation with Helicobacter felis infection; with acute inflammation with L635 treatment; and without inflammation following DMP-777 treatment.RNA transcripts from laser capture microdissected normal chief cells and SPEM lineages were compared using gene microarray. Alterations in transcripts were validated by quantitative real-time PCR. Clusterin and cystic fibrosis transmembrane conductance regulator (CFTR) were selected for immunohistochemical analysis in all mouse models as well as in human SPEM, intestinal metaplasia and gastric cancer.Transcript expression patterns demonstrated differences among the phenotypic SPEM models. Clusterin expression was significantly upregulated in all three mouse SPEM models as well as in human SPEM. The highest clusterin expression in human gastric cancers correlated with poor survival. Conversely, CFTR expression was upregulated only in SPEM with inflammation in mice. In humans, intestinal metaplasia, but not SPEM, expressed CFTR.While markers such as clusterin are expressed in all phenotypic SPEM lineages, distinct patterns of upregulated genes including CFTR are present in murine metaplasia associated with inflammation, indicative of progression of metaplasia towards a more intestinalised metaplastic phenotype.
A natural experiment on the impact of fruit supplementation on asthma symptoms in children
Authors: A. W. Fogarty, M. Antoniak, A. J. Venn, L. Davies, A. Goodwin, N. Salfield, J. R. Britton, S. A. Lewis
Journal: European Respiratory Journal (2009)

A high fruit intake may reduce the risk of asthma. The English National School Fruit Scheme was introduced in the East Midlands region of the UK in June 2003 and in the Eastern region in September 2004. Questionnaires were distributed to children aged 4–6 yrs in schools in May 2003. This was repeated in May 2004 when those in the East Midlands had received free fruit for 1 yr and those in the Eastern region had not. Responses were obtained in 2004 for 4,971 (53%) and 5,770 (54%) children in the intervention and control regions, respectively. Despite an increase in fruit consumption in the intervention compared with the control region between 2003 and 2004, there was no difference between the two regions in the prevalence or severity of asthma symptoms after 1 yr of fruit supplementation (odds ratio for wheeze in the past 12 months in intervention compared with control region 1.00, 95% confidence interval 0.88–1.14). Providing free fruit at school for 1 yr does not have any immediate effect on prevalence or severity of asthma in young children, although these data do not refute the hypothesis that a higher increase in fruit intake improves measures of asthma control.
Renal functional reserve is impaired in patients with systemic sclerosis without clinical signs of kidney involvement
Authors: R Livi
Journal: Annals of the Rheumatic Diseases (2002)

To evaluate the functional response of the kidney to an amino acid challenge (the so called renal functional reserve (RFR)) in patients with systemic sclerosis (SSc) with no clinical sign of renal involvement.Before and after an intravenous amino acid load (Freamine III Baxter, 8.5% solution, 4.16 ml/min for two hours), glomerular filtration rate (GFR, as creatinine clearance), effective renal plasma flow (ERPF, as para-aminohyppurate clearance), and calculated total renal vascular resistance (TRVR) were measured in 21 patients with SSc with apparently normal renal function and 10 normal controls.In basal conditions, patients had lower ERPF (403.5 (SD 43.8) v 496.4 (SD 71.3) ml/min, p<0.0002) and higher TRVR (10 822 (SD 2044) v 8874 (SD 1639) dyne/sxcm(-5), p<0.014) than controls. The RFR, evaluated as the percentage increase of GFR after the amino acid load, was significantly reduced in patients with SSc (SSc +1.9 (SD18.6)%, controls +34.8 (SD 13.9)%; p<0.0002). However, the response of patients was not uniform. Multiple regression analysis showed that the RFR was inversely dependent on the patients' mean arterial pressure at admission and basal GFR (R(2)=65%, p<0.0001).Most patients with SSc cannot increase renal filtration under the challenge of a protein overload. This defective renal response to the amino acid load test sustains the concept of the prevalence of vasoconstrictor over vasodilating factors in the kidney of these patients.
Distribution of therapeutic response in asthma control between oral montelukast and inhaled beclomethasone
Authors: R.A. Baumgartner, G. Martinez, J.M. Edelman, G.G. Rodriguez Gomez, M. Bernstein, S. Bird, R. Angner, A. Polis, S.B. Dass, S. Lu, T.F. Reiss
Journal: European Respiratory Journal (2003)

The distribution of responses in study populations provides a novel method of comparing the benefit of two treatments. This 6‐week, randomised, placebo-controlled, double-blind study compared the effectiveness of oral montelukast with inhaled beclomethasone in chronic asthma by assessing the distribution and overlap of patient responses to therapy, as measured by a clinical outcome (asthma control days). A total of 730 adult patients with asthma, age 15–65 yrs, with a forced expiratory volume in one second (FEV 1 ) at baseline of 50–85% of predicted and ≥15% improvement in FEV 1 after inhaled β‐agonist were enrolled. After a 2–week placebo run-in period, patients were randomly allocated to receive montelukast (10 mg once daily), inhaled beclomethasone (200 µg twice daily) or placebo. The primary end-point (per cent of asthma control days) was compared between treatments as the overlap in the response distributions. The overlap of the distribution of responses between the montelukast and beclomethasone groups was 89% for per cent asthma control days and 96% for change from baseline in FEV 1 . The mean (±sd) per cent asthma control days in the montelukast and beclomethasone groups was significantly higher than that in the placebo group (placebo 40.0±35.8, montelukast 50.7±37.1, beclomethasone 57.9±36.1). The mean differences between montelukast and placebo, beclomethasone and placebo, and montelukast and beclomethasone were significant. The mean per cent change (±sd) from baseline in FEV 1 was 12.1±18.7 and 13.9±20.8 in the montelukast and beclomethasone groups, respectively, and significantly greater than that in the placebo group (6.4±20.1); there was no significant difference between the montelukast and beclomethasone groups in mean values or response distribution. There was also no difference among treatment groups in the frequency of adverse experiences. A comparison of the response distribution is an important approach to comparing therapies; montelukast and beclomethasone provided similar response distributions for the end-point of per cent asthma control days over a 6‐week treatment period.
Cloning and expression of intercellular adhesion molecule 3 reveals strong homology to other immunoglobulin family counter-receptors for lymphocyte function-associated antigen 1.
Authors: A R de Fougerolles, L B Klickstein, T A Springer
Journal: The Journal of Experimental Medicine (1993)

Based on protein sequence, we have isolated a cDNA for intercellular adhesion molecule 3 (ICAM-3), the most recently defined counter-receptor for lymphocyte function-associated antigen 1 (LFA-1). Expression of the cDNA yields a product that reacts with monoclonal antibody to ICAM-3 and functions as a ligand for LFA-1. The deduced 518-amino acid sequence of the predicted mature protein defines a highly glycosylated type I integral membrane protein with five immunoglobulin (Ig)-like domains. The five Ig-like domains of ICAM-3 are highly homologous with those of human ICAM-1 (52% identity) and human ICAM-2 (37% identity).
Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase, in healthy volunteers.
Authors: J A Tobert, G D Bell, J Birtwell, I James, W R Kukovetz, J S Pryor, A Buntinx, I B Holmes, Y S Chao, J A Bolognese
Journal: Journal of Clinical Investigation (1982)

Mevinolin reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The safety and effectiveness of this agent was evaluated in a double-blind, placebo-controlled study in 59 healthy men (serum cholesterol 3.88--7.76 mmol/liter) in five centers. Subjects maintained their usual diet and activities. Doses of 6.25, 12.5, 25, or 50 mg twice daily for 4 wk produced mean reductions of total serum cholesterol fo 23--27% [vs. placebo (4%), P less than 0.01]. Mean low density lipoprotein cholesterol fell 35--45%, while high density lipoprotein and very low density lipoprotein cholesterol, and triglycerides were not significantly affected. Mean apolipoprotein B fell 27--34%. 50 mg was not significantly more effective than 6.25 mg. Mevinolin was generally well tolerated, and no serious clinical or laboratory abnormalities occurred. One subject (12.5 mg) was withdrawn because of abdominal pain and diarrhea. These results suggest that if long-term safety can be demonstrated, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase are likely to prove useful in the treatment of hypercholesterolemia.
Cooperative Interactions of p53 Mutation, Telomere Dysfunction, and Chronic Liver Damage in Hepatocellular Carcinoma Progression
Authors: Paraskevi A. Farazi, Jonathan Glickman, James Horner, Ronald A. DePinho
Journal: Cancer Research (2006)

Abstract Hepatocellular carcinoma is among the most common and lethal cancers in humans. Hepatocellular carcinoma is commonly associated with physical or functional inactivation of the p53 tumor suppressor, high levels of chromosomal instability, and disease conditions causing chronic cycles of hepatocyte death and regeneration. Mounting evidence has implicated regeneration-induced telomere erosion as a potential mechanism fueling genome instability. In mouse models of hepatocellular carcinoma, telomere dysfunction has been shown to enhance initiation of hepatic neoplasias yet constrain full malignant progression of these neoplasms possibly due to activation of a p53-dependent checkpoint and/or intolerable levels of genomic instability. Here, in a hepatocellular carcinoma–prone model brought about through toxin-induced hepatocyte injury and regeneration, we sought to determine the cooperative interactions of germ line p53 mutation and telomere dysfunction [produced by telomerase reverse transcriptase (mTERT) gene knockout]. In the setting of intact telomeres, p53 mutation had no effect on hepatocarcinogenesis, whereas in the setting of telomere dysfunction, p53 mutation enabled advanced hepatocellular carcinoma disease. Notably, there was no evidence of deletion or mutation of the wild-type p53 allele in the late generation mTert−/−p53+/− mice, suggesting that reduced levels of p53 potently enable hepatocellular carcinoma progression in the setting of telomere dysfunction. Thus, this study supports a model that, in the face of chronic liver damage, attenuated p53 function and telomere-induced chromosomal instability play critical and cooperative roles in the progression of hepatocellular carcinoma. (Cancer Res 2006; 66(9): 4766-73)
Differing Evolutionary Histories of WFDC8 (Short-Term Balancing) in Europeans and SPINT4 (Incomplete Selective Sweep) in Africans
Authors: Z. Ferreira, B. Hurle, J. Rocha, S. Seixas
Journal: Molecular Biology and Evolution (2011)

The whey acidic protein four-disulfide core (WFDC) gene cluster on human chromosome 20q13, harbors 15 small serine protease inhibitor genes with roles in innate immunity, reproduction, and regulation of endogenous proteases kallikreins. The WFDC cluster has emerged as a prime example of rapid diversification and adaptive evolution in primates. This study sought a better understanding of the evolutionary history of WFDC genes in humans and focused on exploring the adaptive selection signatures found in populations of European (Utah residents with ancestry from northern and western Europe [CEU]) and African (Yoruba from Ibadan, in Nigeria [YRI]) ancestry in a genome-wide scan for putative targets of recent adaptive selection. Our approach included resequencing coding and noncoding regions of WFDC6, EPPIN, and WFDC8 in 20 CEU and of SPINT4 in 20 YRI individuals. We generated 302 kb and 60 kb of high-quality sequence data from CEU and of YRI populations, respectively, enabling the identification of 72 single nucleotide polymorphisms. Using classic neutrality tests, empirical and haplotype-based analysis, we pinpointed WFDC8 and SPINT4 as the likely targets of short-term balancing selection in the CEU population, and recent positive selection (incomplete selective sweep) in the YRI population. Putative candidate variants targeted by selection include 44A (rs7273669A) for WFDC8, which may downregulate gene expression by abolishing the binding site of two transcription factors; and a haplotype configuration [Ser73+98A] (rs6017667A-rs6032474A) for SPINT4, which may simultaneously affect protein function and gene regulation. We propose that the evolution of WFDC8 and SPINT4 has been shaped by complex selective scenarios due to the interdependence of variant fitness and ecological variables.
Natural Killer Cells Efficiently Reject Lymphoma Silenced for the Endoplasmic Reticulum Aminopeptidase Associated with Antigen Processing
Authors: Loredana Cifaldi, Elisa Lo Monaco, Matteo Forloni, Ezio Giorda, Silvia Lorenzi, Stefania Petrini, Elisa Tremante, Daniela Pende, Franco Locatelli, Patrizio Giacomini, Doriana Fruci
Journal: Cancer Research (2011)

Abstract The endoplasmic reticulum aminopeptidase ERAAP is involved in the final trimming of peptides for presentation by MHC class I (MHC-I) molecules. Herein, we show that ERAAP silencing results in MHC-I peptide-loading defects eliciting rejection of the murine T-cell lymphoma RMA in syngeneic mice. Although CD4 and CD8 T cells are also involved, rejection is mainly due to an immediate natural killer (NK) cell response and depends on the MHC-I-peptide repertoire because replacement of endogenous peptides with correctly trimmed, high-affinity peptides is sufficient to restore an NK-protective effect of MHC-I molecules through the Ly49C/I NK inhibitory receptors. At the crossroad between innate and adaptive immunity, ERAAP is therefore unique in its two-tiered ability to control tumor immunogenicity. Because a large fraction of human tumors express high levels of the homologous ERAP1 and/or ERAP2, the present findings highlight a convenient, novel target for cancer immunotherapy. Cancer Res; 71(5); 1597–606. ©2011 AACR.
Stillbirths, Sudden Infant Deaths, and Long-QT Syndrome
Authors: Peter J. Schwartz
Journal: Circulation (2004)

tillbirths contribute substantially to perinatal mortality in developed countries. 12][3] Despite careful investigation, at least 25%, 4 and possibly 50%, 1 remain unexplained.Another mysterious cause of early sudden death is represented by sudden infant death syndrome (SIDS), 5,6 which is still the leading cause of mortality during the first year of life.Finally, a relatively large number of sudden deaths in the young (infants, children, and teenagers) is due to long-QT syndrome (LQTS). 7-10Are these entities completely unrelated or is there a link between them, such that the latter might be a contributor to the former?As a matter of fact, this specific hypothesis has already been proposed. 11,12Its interest lies in the fact that, beyond the scientific and conceptual implications, if proven correct it could offer an opportunity to prevent those fetal or infant deaths sharing the same genetic and arrhythmogenic mechanism.
Characterization of human rheumatoid factors with seven antiidiotypes induced by synthetic hypervariable region peptides.
Authors: P P Chen, F Gõni, R A Houghten, S Fong, R Goldfien, J H Vaughan, B Frangione, D A Carson
Journal: The Journal of Experimental Medicine (1985)

Recently, we have used synthetic peptides corresponding to the complementarity-determining regions (CDR) of Ig molecules to induce antiidiotypic antisera. Peptide PSH3, representing the third CDR of the IgM rheumatoid factor (RF) Sie heavy (H) chain, induced a private antiidiotype that reacted with only one out of five IgM-RF. Peptide PSL2, corresponding to the second CDR of Sie light (L) chain, induced an antibody against a crossreactive idiotype (CRI), expressed by 10 out of 12 human IgM-RF analyzed. Herein, we report that five additional antiidiotypic antibodies were generated by immunization with synthetic peptides identical to the third L chain CDR of IgM-RF Sie (PSL3), the second and third H chain CDR of IgM-RF Wol, and the second and third CDR of IgM-RF Pom. As analyzed by immunoblot assay, both anti-PSL3 and anti-PSL2 reacted with the majority of 16 IgM-RF. In contrast, all five antiidiotypes induced by the H chain peptides reacted only with the parent proteins, except anti-PSH3, which reacted weakly with one additional RF. These results suggest that one (or very few) VL gene(s), but a larger number of VH genes, are used to encode IgM-RF autoantibodies.
Defibrillatory Effects of Low Sodium Solutions on Ventricular Fibrillation in Isolated Hearts of Rabbits
Authors: LEONARD GRUMBACH, J. Wimbert, A. K. Pierson
Journal: Circulation Research (1957)

Isolated hearts in ventricular fibrillation can be defibrillated without interfering with the conduction of normal impulses arriving from the atria by the perfusion of solutions containing only about half of the normal sodium content. Reversion to a sinus rhythm occurs without a pause. The action of these solutions, which closely resembles that of normal solutions containing an excess of KCl or procaine, supports the hypothesis that these agents defibrillate by interfering with the entrance of sodium ions in the rising phase of the action potential. Defibrillation by this mechanism would be possible if ventricular fibrillation were the result of the discharge of premature impulses having a low safety factor of propagation from one or more ectopic foci.