tbuckley/cabot-search huggingface dataset:
Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral Regurgitation
Authors: Michael A. Acker, Michael K. Parides, Louis P. Perrault, Alan J. Moskowitz, Annetine C. Gelijns, Pierre Voisine, Peter K. Smith, Judy W. Hung, Eugene H. Blackstone, John D. Puskas, Michael Argenziano, James S. Gammie, Michael Mack, Deborah D. Ascheim, Emilia Bagiella, Ellen G. Moquete, T. Bruce Ferguson, Keith A. Horvath, Nancy L. Geller, Marissa A. Miller, Y. Joseph Woo, David A. D'Alessandro, Gorav Ailawadi, Francois Dagenais, Timothy J. Gardner, Patrick T. O'Gara, Robert E. Michler, Irving L. Kron
Journal: New England Journal of Medicine (2013)

Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited.
Evaluation of the addition of cromolyn sodium to bronchodilator maintenance therapy in the long-term management of asthma
Authors: H EIGEN, J REID, R DAHL, C DELBUFALO, L FASANO, G GUNELLA, K SAHLSTROM, K ALANKO, J GREENBAUM, C HAGELUND
Journal: Journal of Allergy and Clinical Immunology (1987)
Raised MCP-4 levels in symptomatic carotid atherosclerosis: an inflammatory link between platelet and monocyte activation
Authors: Unni M. Breland, Annika E. Michelsen, Mona Skjelland, Lasse Folkersen, Kirsten Krohg-Sørensen, David Russell, Thor Ueland, Arne Yndestad, Gabrielle Paulsson-Berne, Jan K. Damås, Erik Øie, Gøran K. Hansson, Bente Halvorsen, Pål Aukrust
Journal: Cardiovascular Research (2010)

Several studies suggest a pro-atherogenic role for the CC chemokine receptor 2 (CCR2), thought to reflect interaction with monocyte chemoattractant protein (MCP)-1. Based on its ability to attract leucocytes into inflamed tissue, we hypothesized a pro-atherogenic role for MCP-4, another CCR2 ligand. Our main findings were: (i) patients with symptomatic carotid stenosis (n = 29), but not those with asymptomatic plaques (n = 31), had significantly raised plasma levels of MCP-4 compared with healthy controls (n = 20); (ii) in vitro, releasate from activated platelets markedly increased the expression of MCP-4 and CCR2 in THP-1 monocytes, and enhanced the MCP-4-mediated effect on interleukin-8 secretion in these cells, involving the platelet-derived chemokine RANTES; (iii) while MCP-1 had no effect on the release of RANTES and interferon-inducible protein of 10 kDa in tumour necrosis factor α-pre-activated THP-1 monocytes, MCP-4 profoundly enhanced the release of these pro-atherogenic chemokines; and (iv) the data indicate an inflammatory interaction between RANTES and MCP-4, involving CCR2, and mRNA levels of these mediators were markedly up-regulated within symptomatic atherosclerotic carotid plaque (n = 81). Our findings suggest that the pro-atherogenic effects of CCR2 may not be restricted to interaction with MCP-1, but could also involve activation by MCP-4, being an inflammatory link between platelet and monocyte activation.
Down syndrome: lip lesions (angular stomatitis and fissures) and Candida albicans
Authors: C. Scully, W. Van Bruggen, P. Diz Dios, B. Casal, S. Porter, M-F. Davison
Journal: British Journal of Dermatology (2002)

The incidence of angular cheilitis (angular stomatitis, perleche, commissural fissures) appears to be increased in people with Down syndrome (DS). Lip fissures are also (in our clinical impression) a fairly regular feature, yet this is scarcely mentioned in the literature.To establish the incidence of angular cheilitis and lip fissures in a substantial group of patients with DS and to examine the relationship with Candida albicans.The prevalence of orofacial soft tissue lesions was investigated in a group of 77 DS patients. Swabs were taken from lip lesions, palate and tongue and inoculated on Sabouraud's agar discs for the isolation of C. albicans, identified with commercially available kits.Lip fissures were seen in at least one-quarter of DS patients. Angular cheilitis was also found in a similar percentage.C. albicans was isolated from a substantial proportion of lesions tested, and was present more frequently than in those without lip lesions, but it is uncertain whether this represents cause or effect.
Randomized Study on the Efficacy of Cognitive-Behavioral Therapy for Insomnia Secondary to Breast Cancer, Part II: Immunologic Effects
Authors: Josée Savard, Sébastien Simard, Hans Ivers, Charles M. Morin
Journal: Journal of Clinical Oncology (2005)

Purpose Cross-sectional studies suggest that clinical insomnia is associated with immune downregulation. However, there is a definite need for experimental studies on this question. The goal of this randomized controlled study was to assess the effect of an 8-week cognitive-behavioral therapy (CBT) for chronic insomnia on immune functioning of breast cancer survivors. Previous analyses of this study showed that CBT was associated with improved sleep and quality of life, and reduced psychological distress. Patients and Methods Fifty-seven women with chronic insomnia secondary to breast cancer were randomly assigned to CBT (n = 27) or to a waiting-list control condition (WLC; n = 30). Peripheral-blood samples were taken at baseline and post-treatment (and postwaiting for WLC patients), as well as at 3-, 6-, and 12-month follow-up for immune measures, including enumeration of blood cell counts (ie, WBCs, monocytes, lymphocytes, CD3 + , CD4 + , CD8 + , and CD16 + /CD56 + ) and cytokine production (ie, interleukin-1-beta [IL-1β] and interferon gamma [IFN-γ]). Results Patients treated with CBT had higher secretion of IFN-γ and lower increase of lymphocytes at post-treatment compared with control patients. Pooled data from both treated groups indicated significantly increased levels of IFN-γ and IL-1β from pre- to post-treatment. In addition, significant changes in WBCs, lymphocytes, and IFN-γ were found at follow-up compared with post-treatment. Conclusion This study provides some support to the hypothesis of a causal relationship between clinical insomnia and immune functioning. Future studies are needed to investigate the clinical impact of such immune alterations.
Effects of Dietary Polyunsaturated and Saturated Fat on the Properties of High Density Lipoproteins and the Metabolism of Apolipoprotein A-I
Authors: James Shepherd, Christopher J. Packard, Josef R. Patsch, Antonio M. Gotto, O. David Taunton
Journal: Journal of Clinical Investigation (1978)

In this study we have investigated, in four normal males the effects of dietary saturated and polyunsaturated fat on the chemical composition and thermotropic properties of human high density lipoproteins (HDL) and have measured the influence of the diets on the metabolism of that fraction of HDL apolipoprotein A-I (apoA-I) that undergoes exchange in vitro and accounts for approximately two-thirds of the lipoprotein's apoA-I complement. When compared with the saturated fat diet, the polyunsaturated diet reduced plasma cholesterol (24%, P < 0.01) by affecting the cholesterol content in the very low density lipoprotein (↓25%, P < 0.02), low density lipoprotein (↓20%, P < 0.01), and high density lipoprotein fractions (↓33%, P < 0.01). Plasma triglyceride was also lowered (by 13%, P < 0.01). Furthermore, polyunsaturated fat ingestion caused a significant fall in the palmitate and stearate content of HDL triglyceride (41 and 37%, respectively), cholesteryl esters (29 and 35%), and phospholipids (17 and 9%) with a concomitant increase in the linoleate content of these moieties (157, 28, and 29%, respectively). The polyunsaturated diet also produced reciprocal changes in the percentage protein (↓9%, P < 0.02) and phospholipid (↓11.5%, P < 0.01) in HDl. These compositional changes were associated with an increase in the microscopic fluidity of the polyunsaturated HDL, although both diets had little effect on the fluidity parameters of HDL at body temperature. Rate zonal ultracentrifugation indicated that the HDL2/HDL3 ratio fell by 28% (P < 0.05) on the polyunsaturated fat diet. In addition to the above, this diet reduced plasma apoA-I by 21% (P < 0.01). No change was seen in the fractional catabolic rate or the distribution of the apoprotein between intravascular and extravascular compartments on the two diets. However, when compared with the saturated diet, the synthetic rate of apoA-I was reduced by 26% during polyunsaturated fat feeding. The results show that polyunsaturated fat alters the chemical composition, thermotropic properties, and subfraction distribution of HDL without changing the fractional rate of catabolism of their major protein, apoA-I.
The association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with OSA: a meta-analysis
Authors: Peilin Lee, Neil J. Douglas, Renata L. Riha
Journal: European Respiratory Journal (2011)

Obstructive sleep apnoea (OSA) is an independent risk factor for hypertension. Increased angiotensin-converting enzyme (ACE) activity may be a possible promoting mechanism with different ACE insertion/deletion (I/D) genotypes influencing this activity. Studies investigating the association of ACE I/D polymorphisms with OSA have shown conflicting results. We aimed to undertake a meta-analysis of existing studies exploring the association of ACE I/D polymorphisms with the risk of OSA and hypertension. 10 studies were included in a random effects meta-analysis, comprising 1,227 OSA subjects and 1,227 controls. The effect size was measured using the odds ratio. The risk of having OSA in carriers of the D allele was 0.92 (95% CI 0.69–1.23). There was statistically significant heterogeneity across the studies (I 2 =42%, p=0.08 and I 2 =74%, p&lt;0.0001 for genotype and allele frequency, respectively). The association of D allele frequency with the risk of OSA remained nonsignificant after stratification based on ethnicity, source of population sample, and the presence of hypertension. Subgroup analysis failed to show any influence of genotype and allele frequency on OSA severity. This meta-analysis revealed no association between the ACE I/D polymorphisms and OSA susceptibility.
Retinoids for Ovarian Cancer Prevention: Laboratory Data Set the Stage for Thoughtful Clinical Trials
Authors: U. Veronesi, A. Decensi
Journal: JNCI Journal of the National Cancer Institute (2001)

Ovarian cancer is a highly lethal disease and represents one of the leading causes of cancer death among women in Western countries. Since effective methods of screening and early diagnosis are lacking, prevention is being sought as one of the most promising ways to reduce mortality. While prophylactic oophorectomy is increasingly used for high-risk women, its short- and long-term morbidity is unknown. More important, most ovarian cancers are sporadic, and the widespread use of prophylactic oophorectomy in average-risk women is unimaginable. An epidemiologic study (1) has shown that oral contraceptive use is associated with reduced ovarian cancer risk among the general population as well as in BRCA1 heterozygotes. In women with a family history of breast cancer, however, oral contraceptive use is associated with additional risk of that disease (2). Thus, other agents are being studied that might replace or be combined with oral contraceptives for prevention of ovarian cancer. Among these agents, retinoids have been the subject of the most intensive investigation of their potential to prevent cancer (3). The first evidence of an in vivo effect by retinoids on ovarian cancer came from the study by Formelli and Cleris (4) using the retinoic acid analogue fenretinide (N-4-hydroxyphenylretinamide). The potential of retinoids for the prevention of ovarian cancer was subsequently confirmed in the phase III trial of fenretinide for the reduction in the incidence of second breast cancer (5). During the 5-year intervention period, a statistically significant lower incidence of ovarian cancer was noted in the fenretinide group compared with the control group (no cases versus six cases, respectively) (6). However, because of the unexpected results and the limited number of events, the observation should be viewed with extreme caution. In addition, the apparent benefit was partially lost during the subsequent followup period, suggesting that the potential preventive effect of fenretinide was not lasting and that treatment would have to be continued indefinitely for the benefit to continue (5). However, attention to secondary clinical trial endpoints often yields new hypotheses for exploration. Thus, the finding prompted different laboratories to provide further insight into this clinical finding. Since that initial clinical observation (6), several in vivo and in vitro studies (4,7–9) have consistently shown that fenretinide,
Immune-inflammatory functions of fibroblasts
Authors: M Jordana, B Sarnstrand, PJ Sime, I Ramis
Journal: European Respiratory Journal (1994)

Inflammation is a response that has evolved over millions of years to become an extremely complex process. This complexity reflects the host's need to deal effectively with a wide variety of potentially injurious agents, as well as the need to incorporate an adequate set of checks and balances. An inappropriately checked response, which occurs rarely, results in disease, either acute or chronic. However, in most instances, inflammation is a beneficial response, essential for survival. Inflammation comprises an extensive network of cellular interactions implemented by an overwhelming number of molecules. One category of signal includes soluble products, such as neuropeptide, lipid mediators, cytokines and growth factors, most of which can be produced by inflammatory/haemopoietic cells. However, resident structural cells can also produce many of these products and, on this basis only, fibroblasts, epithelial, endothelial and smooth muscle cells should be considered as active contributors to the regulation of the inflammatory response. Extracellular matrix (ECM) proteins comprise another category of signals. Whilst the most recognized activities of these proteins are those concerned with providing structural tissue integrity, it is clear that they also have powerful inductive effects. Indeed, ECM proteins can influence the shape, movement and state of activation of inflammatory cells in the tissue. Recent evidence indicates that these signals may also play substantial roles in homing of inflammatory cells to certain sites and in the handling of a number of cytokines and growth factors. In so far as fibroblasts are the main producers of ECM proteins, these new data establish an indirect but important role for fibroblasts in the regulation of the inflammatory response.
Ribosomal scanning past the primary initiation codon as a mechanism for expression of CTL epitopes encoded in alternative reading frames.
Authors: T N Bullock, L C Eisenlohr
Journal: The Journal of Experimental Medicine (1996)

An increasing amount of evidence has shown that epitopes restricted to MHC class I molecules and recognized by CTL need not be encoded in a primary open reading frame (ORF). Such epitopes have been demonstrated after stop codons, in alternative reading frames (RF) and within introns. We have used a series of frameshifts (FS) introduced into the Influenza A/PR/8 /34 nucleoprotein (NP) gene to confirm the previous in vitro observations of cryptic epitope expression, and show that they are sufficiently expressed to prime immune responses in vivo. This presentation is not due to sub-dominant epitopes, transcription from cryptic promoters beyond the point of the FS, or internal initiation of translation. By introducing additional mutations to the construct exhibiting the most potent presentation, we have identified initiation codon readthrough (termed scanthrough here, where the scanning ribosome bypasses the conventional initiation codon, initiating translation further downstream) as the likely mechanism of epitope production. Further mutational analysis demonstrated that, while it should operate during the expression of wild-type (WT) protein, scanthrough does not provide a major source of processing substrate in our system. These findings suggest (i) that the full array of self- and pathogen-derived epitopes available during thymic selection and infection has not been fully appreciated and (ii) that cryptic epitope expression should be considered when the specificity of a CTL response cannot be identified or in therapeutic situations when conventional CTL targets are limited, as may be the case with latent viral infections and transformed cells. Finally, initiation codon readthrough provides a plausible explanation for the presentation of exocytic proteins by MHC class I molecules.
<b> <i>BRAF</i> </b> Mutation Is Frequently Present in Sporadic Colorectal Cancer with Methylated hMLH1, But Not in Hereditary Nonpolyposis Colorectal Cancer
Authors: Guoren Deng, Ian Bell, Suzanne Crawley, James Gum, Jonathan P. Terdiman, Brian A. Allen, Brindusa Truta, Marvin H. Sleisenger, Young S. Kim
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The BRAF gene encodes a serine/threonine kinase and plays an important role in the mitogen-activated protein kinase signaling pathway. BRAF mutations in sporadic colorectal cancer with microsatellite instability (MSI) are more frequently detected than those in microsatellite stable cancer. In this study, we sought to compare the frequencies of BRAF mutations in sporadic colorectal cancer with MSI with those in hereditary nonpolyposis colorectal cancer (HNPCC). Experimental Design: We analyzed BRAF mutations in 26 colorectal cancer cell lines, 80 sporadic colorectal cancers, and 20 tumors from HNPCC patients by DNA sequencing and sequence-specific PCR. The methylation status of the hMLH1 gene was measured by either sequencing or restriction enzyme digestion after NaHSO3 treatment. Results: We observed a strong correlation of BRAF mutation with hMLH1 promoter methylation. BRAF mutations were present in 13 of 15 (87%) of the colorectal cell lines and cancers with methylated hMLH1, whereas only 4 of 91 (4%) of the cell lines and cancers with unmethylated hMLH1 carried the mutations (P &amp;lt; 0.00001). Sixteen of 17 mutations were at residue 599 (V599E). A BRAF mutation was also identified at residue 463 (G463V) in one cell line. In addition, BRAF mutations were not found in any cancers or cell lines with K-ras mutations. In 20 MSI+ cancers from HNPCC patients, however, BRAF mutations were not detectable, including a subset of 9 tumors with negative hMLH1 immunostaining and methylated hMLH1. Conclusions: BRAF mutations are frequently present in sporadic colorectal cancer with methylated hMLH1, but not in HNPCC-related cancers. This discrepancy of BRAF mutations between sporadic MSI+ cancer and HNPCC might be used in a strategy for the detection of HNPCC families.
NG2 expression in glioblastoma identifies an actively proliferating population with an aggressive molecular signature
Authors: M. T. F. Al-Mayhani, R. Grenfell, M. Narita, S. Piccirillo, E. Kenney-Herbert, J. W. Fawcett, V. P. Collins, K. Ichimura, C. Watts
Journal: Neuro-Oncology (2011)

Glioblastoma multiforme (GBM) is the most common type of primary brain tumor and a highly malignant and heterogeneous cancer. Current conventional therapies fail to eradicate or curb GBM cell growth. Hence, exploring the cellular and molecular basis of GBM cell growth is vital to develop novel therapeutic approaches. Neuroglia (NG)-2 is a transmembrane proteoglycan expressed by NG2+ progenitors and is strongly linked to cell proliferation in the normal brain. By using NG2 as a biomarker we identify a GBM cell population (GBM NG2+ cells) with robust proliferative, clonogenic, and tumorigenic capacity. We show that a significant proportion (mean 83%) of cells proliferating in the tumor mass express NG2 and that over 50% of GBM NG2+ cells are proliferating. Compared with the GBM NG2− cells from the same tumor, the GBM of NG2+ cells overexpress genes associated with aggressive tumorigenicity, including overexpression of Mitosis and Cell Cycling Module genes (e.g., MELK, CDC, MCM, E2F), which have been previously shown to correlate with poor survival in GBM. We also show that the coexpression pattern of NG2 with other glial progenitor markers in GBM does not recapitulate that described in the normal brain. The expression of NG2 by such an aggressive and actively cycling GBM population combined with its location on the cell surface identifies this cell population as a potential therapeutic target in a subset of patients with GBM.
Improve reporting of female genital mutilation, MPs tell doctors
Authors: A. O'Dowd
Journal: BMJ (2015)

Two hundred and fifty one cases of penetrating wounds of the chest were studied prospectively. Clinical evidence is presented to show that: basal intercostal drains are adequate to remove both air and fluid from within the pleural cavity; frequent chest radiographs are unnecessary and intercostal drains may be removed on clinical grounds alone; long term antibiotic prophylaxis is unnecessary; eight per cent of those undergoing initial observation will develop a delayed haemothorax or pneumothorax of sufficient size to require drainage; subcutaneous emphysema is of no prognostic significance in the symptomless patient with minimal intrapleural damage on admission; and outpatient follow up is not required.
Drug Therapies for the Primary Prevention of Cardiovascular Events: Trials and Errors
Authors: Bruce M. Psaty
Journal: Circulation (2010)

Blackburn entitled his introduction to the first Ancel Keys lecture "Ancel Keys, pioneer" and summarized Keys' astonishing array of work in nutrition and physiology, methods, and prevention, including the diet-heart hypothesis and efforts to bridge biology, preventive medicine, and public health. 2As a result of his work and the work of many others over the last 50 years, the mortality rate from coronary heart disease (CHD) declined by about 50% between 1980 and 2000, a decline attributable in part to changes in medical treatments after coronary events and in part to changes in levels of risk factors in the population. 3In this lecture, as an admiring follower and a northwest settler, I consider some potential next steps in CHD prevention.This talk has 2 related parts.The first reviews how we approve preventive drug therapies in America.High-quality drug evaluations serve as an essential foundation for future CHD prevention efforts.The second part considers 2 potential approaches to the use of drug therapies in intermediaterisk individuals for the primary prevention of CHD.The first involves using novel biomarkers to improve risk prediction and to target treatment to those newly identified as high-risk individuals.The second involves simply expanding the eligibility for well-evaluated drugs to the entire group of intermediate-risk individuals.A comparative effectiveness trial evaluating the risks and benefits of these 2 approaches would help guide future prevention efforts.
Functional organ preservation with definitive chemoradiotherapy for T4 laryngeal squamous cell carcinoma
Authors: B.R. Knab, J.K. Salama, A. Solanki, K.M. Stenson, E.E. Cohen, M.E. Witt, D.J. Haraf, E.E. Vokes
Journal: Annals of Oncology (2008)
IgA nephropathy associated with ankylosing spondylitis: occurrence in women as well as in men.
Authors: K N Lai, P K Li, B Hawkins, F M Lai
Journal: Annals of the Rheumatic Diseases (1989)

Two patients (one male, one female) with ankylosing spondylitis (AS) and IgA nephropathy are described. The female patient is the first reported case to have AS and IgA nephropathy concurrently. Contrary to previously reported cases, her renal manifestation preceded her rheumatic symptoms. It is suggested that women with IgA nephropathy and AS may be overlooked as the severity of spondylitis and joint involvement is less than in men.