tbuckley/cabot-search huggingface dataset:
The Prognostic Value of Isolated Tumor Cells in Bone Marrow in Breast Cancer Patients
Authors: Bjørn Naume, Gro Wiedswang, Elin Borgen, Gunnar Kvalheim, Rolf Kåresen, Hanne Qvist, Jan Janbu, Torstein Harbitz, Jahn M. Nesland
Journal: Clinical Cancer Research (2004)

Abstract Purpose/Experimental Design: Immunocytochemical detection of isolated tumor cells (ITCs) in the bone marrow (BM) is a prognostic factor in breast cancer. However, hematopoietic cells (HCs) can occasionally be stained by the techniques used. Morphological evaluation improves the specificity of ITC detection, but optimal separation of ITCs from false-positive HCs needs to be determined. Here, predetermined morphological categories of immunocytochemically (ICC)-positive cells in the BM and the number of detected ITCs were analyzed for association with clinical outcome in 817 early-stage breast cancer patients (median 49 months of follow-up). All ICC+ cells detected were categorized into one of the following groups: (a) tumor cell (TC); (b) uninterpretable cell (UIC); (c) probable HC; or (d) HC. Results: Among the TC+ patients, 30.6% and 25.9% experienced systemic relapse (SR) and breast cancer death (BCD), respectively, as compared with 13.3% and 8.5% of patients without TCs in the BM (survival analyses: P &amp;lt; 0.001, log-rank). The SR and BCD rate was 19.7% and 15.8% for TC−/UIC+ patients versus 12.5% and 7.4% for TC−/UIC− patients. Survival analyses confirmed that the UIC+ group contained clinically significant cells (P = 0.018, log-rank). No difference in clinical outcome was observed, regardless of whether probable HCs or HCs were present. Analyzing the number of ITC+ cells, SR and BCD occurred in 12.4% and 7.4% of patients with 0 ITCs present, 21.3% and 18.5% of patients with 1 ITC present, 19.4% and 16.7% of patients with 2 ITCs present, and 42.5% and 32.5% of patients with ≥3 ITCs present. Conclusions: Morphological categorization of ICC+ cells improves the clinical value of ITC detection in the BM. The presence of only one ITC reduces survival, and a greater number of ITCs further aggravates the prognosis.
Prokineticin receptor 1 (PKR1) signalling in cardiovascular and kidney functions
Authors: M. Boulberdaa, K. Urayama, C. G. Nebigil
Journal: Cardiovascular Research (2011)

Prokineticins (PK1 and PK2) are peptide hormones that exert their biological activity via two common G-protein-coupled receptors: prokineticin receptor (PKR) 1 and 2. Their physiology was originally explored mostly in the context of angiogenic actions in the reproductive tract and gut motility. Since autocrine and paracrine loops have been established between PK2 and PKR1 in the heart, in this review we focus on the PK2/PKR1 signalling in the functions of the heart and kidney. PKR1 signalling is required for cardiomyocyte survival and angiogenesis. In the mouse model of myocardial infarction, intracardiac transient PKR1 transfection protects the structure and function of the heart. Gain- and loss-of-function studies reveal that PKR1 in mouse heart up-regulates its own ligand and PK2, which in turn acts as a paracrine signal and promotes epicardin-positive progenitor cell differentiation into a vasculogenic cell type. Transgenic mice over-expressing PKR1 in cardiomyocytes exhibit increased neovascularization. Loss of PKR1 causes structural and functional changes in the heart and kidney. In isolated epicardin-positive progenitor cells from the kidney, PK2, acting via PKR1, stimulates differentiation of these progenitor cells into endothelial and smooth muscle cells. Taken together, these data show that PK2/PKR1 is involved in postnatal cardiac and renal neovascularization. The knowledge gained from these studies should facilitate the discovery of therapeutic interventions in heart and kidney diseases targeting PKR1.
Endoscopic treatment of gastrointestinal fistulas using an over-the-scope clip (OTSC) device: Case series from a tertiary referral center
Authors: R. Manta, M. Manno, H. Bertani, C. Barbera, F. Pigò, V. Mirante, E. Longinotti, G. Bassotti, R. Conigliaro
Journal: Endoscopy (2011)

Gastrointestinal perforations and post-surgical fistulas are dreaded complications that dramatically increase morbidity and mortality. A new endoscopic over-the-scope clip (OTSC) system may be potentially useful for sealing visceral perforations in several clinical settings. We evaluated the advantages and clinical impact of the placement of OTSCs on the management of non-malignant gut leaks in 12 consecutive patients. OTSCs of 9.5 or 10.5 mm were used, according to the diameter of the defect within the wall. The indications for treatment were mainly related to post-surgical fistulas. Healing of the fistula was assessed by endoscopic or radiological means, and failed only once. No OTSC-related complications occurred. Endoscopic closure of perforations and post-surgical fistulas with the OTSC system is a simple and minimally invasive technique. This approach, when feasible, may be less expensive and more advantageous than a surgical approach.
Magnetic Resonance Reporter Gene Imaging
Authors: Sheen-Woo Lee, Sang-Hoon Lee, Sandip Biswal
Journal: Theranostics (2012)

Molecular imaging has undergone an explosive advancement in recent years, due to the tremendous research efforts made to understand and visualize biological processes. Molecular imaging by definition assesses cellular and molecular processes in living subjects, with the targets of following metabolic, genomic, and proteomic events. Furthermore, reporter gene imaging plays a central role in this field. Many different approaches have been used to visualize genetic events in living subjects, such as, optical, radionuclide, and magnetic resonance imaging. Compared with the other techniques, magnetic resonance (MR)-based reporter gene imaging has not occupied center stage, despite its superior three-dimensional depictions of anatomical details. In this article, the authors review the principles and applications of various types of MR reporter gene imaging technologies and discuss their advantages and disadvantages.
Cross-Talk between the Kidney and the Cardiovascular System
Authors: Kerstin Amann, Christoph Wanner, Eberhard Ritz
Journal: Journal of the American Society of Nephrology (2006)

In recent years, increasing evidence has been provided that even minor renal dysfunction is a powerful cardiovascular risk factor that induces typical cardiovascular alterations and thus predisposes to coronary heart disease as well as to noncoronary cardiovascular problems. This first had been noted in patients with diabetes but now has been confirmed amply in patients without diabetes as well. Numerous heterogeneous abnormalities have been described in patients with early renal dysfunction (e.g., microalbuminuria, reduced estimated GFR). One final common pathway seems to be endothelial cell dysfunction. The link between albuminuria and generalized endothelial cell dysfunction (as indicated by diminished flow-mediated vasodilation, markers of endothelial cell dysfunction, sloughed off endothelial cells, and high transcapillary albumin escape rate) is unclear. In patients with early renal dysfunction, a long list of classical and nonclassical cardiovascular risk factors have been identified: Elevated asymmetric dimethyl-l-arginine concentrations, markers of microinflammation, oxidative stress, features of metabolic syndrome, abnormal adipokine concentrations, dyslipidemia, inappropriate activation of the renin-angiotensin system, and sympathetic overactivity. The mechanisms that link dysfunction of the kidney and the cardiovascular system are being sought. The most interesting unifying concept, however, is deranged fetal programming linking nephron underdosing to the increased cardiovascular risk.
The CCR5- 32 mutation: impact on disease outcome in individuals with hepatitis C infection from a single source
Authors: C Goulding
Journal: Gut (2005)

<b>Background and aims:</b> Chemokines are small polypeptides, a major function of which is lymphocyte recruitment and trafficking. The aim of this study was to assess the involvement of inherited variations in CCR2, CCR5, and the ligand RANTES in determining disease outcome in hepatitis C virus (HCV) infected individuals. <b>Methods:</b> A total of 283 women, all exposed to HCV genotype 1b from a single donor, and including those who had spontaneously cleared the virus and those chronically infected, were genotyped for CCR2, CCR5, and RANTES polymorphisms. The frequencies of these polymorphisms were then compared with disease activity and severity. <b>Results:</b> CCR5, CCR2, and RANTES genotypes were compared with HCV polymerase chain reaction (PCR) status, alanine aminotransferase levels, and liver histology. There was no significant relationship between CCR2 or RANTES polymorphisms and disease outcome or severity. However, CCR5Δ32 heterozygotes were more likely to have spontaneous clearance of the virus than those without the mutation (42% PCR negative <i>v</i> 28.3% negative; p = 0.044, odds ratio 1.83 (95% confidence interval 1.1–3.6)). Among the subgroup of DRB1*03011 negative individuals, previously found to be associated with more severe inflammation, the difference in histological inflammatory score (CCR5WT/WT = 4.9 <i>v</i> CCR5Δ32/WT = 3.53; p = 0.043) was significant. <b>Conclusion:</b> Heterozygosity for CCR5Δ32 was shown to be significantly associated with spontaneous hepatitis C viral clearance and with significantly lower hepatic inflammatory scores in subgroups within this cohort. Both controls and the HCV population had similar heterozygosity frequencies.
Large-scale and high-confidence proteomic analysis of human seminal plasma.
Authors: Bartosz Pilch, Matthias Mann
Journal: Genome biology (2006)

Abstract Background The development of mass spectrometric (MS) techniques now allows the investigation of very complex protein mixtures ranging from subcellular structures to tissues. Body fluids are also popular targets of proteomic analysis because of their potential for biomarker discovery. Seminal plasma has not yet received much attention from the proteomics community but its characterization could provide a future reference for virtually all studies involving human sperm. The fluid is essential for the survival of spermatozoa and their successful journey through the female reproductive tract. Results Here we report the high-confidence identification of 923 proteins in seminal fluid from a single individual. Fourier transform MS enabled parts per million mass accuracy, and two consecutive stages of MS fragmentation allowed confident identification of proteins even by single peptides. Analysis with GoMiner annotated two-thirds of the seminal fluid proteome and revealed a large number of extracellular proteins including many proteases. Other proteins originated from male accessory glands and have important roles in spermatozoan survival. Conclusion This high-confidence characterization of seminal plasma content provides an inventory of proteins with potential roles in fertilization. When combined with quantitative proteomics methodologies, it should be useful for studies of fertilization, male infertility, and prostatic and testicular cancers.
The molecular evolution of the alcohol dehydrogenase locus and the phylogeny of Hawaiian Drosophila.
Authors: R H Thomas, J A Hunt
Journal: Molecular Biology and Evolution (1991)

DNA sequences in the alcohol dehydrogenase genes of flies representing the major groups of Hawaiian Drosophila are used to clarify the relationships of these groups, among themselves and with mainland Drosophila. The topology of the tree derived from these sequences agrees with karyotypic and morphological data but disagrees, in part, with the results of an earlier study that used immunological comparisons between variants of a larval hemolymph protein. A time scale, derived from a comparison of closely related Hawaiian Drosophila species, provides divergence-time estimates that are substantially more recent than those obtained from the immunological studies, although they are still within the bounds set by fossil and biogeographical evidence. The two major lineages of Hawaiian Drosophila, the scaptomyzoids and the drosophiloids, are shown to be widely separated from one another. The scaptomyzoids appear to have diverged early in the history of the subgenus Drosophila, greater than 25 Mya. While hundreds of scaptomyzoid species are found in the Hawaiian archipelago, many fewer are found elsewhere around the world, suggesting that they could have originated outside Hawaii. The drosophiloid lineage is strictly endemic to Hawaii and originated little more than 10 Mya, according to the alcohol dehydrogenase molecular clock. Thus, Drosophila apparently inhabited the Hawaiian archipelago (greater than or equal to 5 Myr before the emergence of the oldest existing high island, Kauai, 5 Mya.
Reply to: Forget personalized medicine and focus on abating disease activity
Authors: William Samuel Wilke
Journal: Annals of the Rheumatic Diseases (2013)

The viewpoint ‘Forget personalised medicine and focus on abating disease activity’1 contends that similar clinical outcomes and converging mechanisms of action observed with biologic therapies make irrelevant use of biomarkers to personalise the use of targeted therapies in rheumatoid arthritis (RA). The authors posit that treatment responses to the second and third anti-tumour necrosis factor (TNF) agent or a change to another biologic agent in randomised, placebo-controlled trials (RPCTs) are strikingly similar for all agents at the population level. They also cite RPCTs that failed to demonstrate additive benefit to combined agents, whereas other studies are considered exceptions. In this opinion, I propose that three premises be satisfied in order to support the validity of the authors’ arguments:

First premise:

A comprehensive review of all relevant RPCTs, including those of drugs in development and combination therapies, must be included in this analysis to definitely show no demonstrable …
Use of Partially Mismatched Related Donors Extends Access to Allogeneic Marrow Transplant
Authors: P. Jean Henslee-Downey, Sunil H. Abhyankar, Rudolph S. Parrish, Asim R. Pati, Kamar T. Godder, William J. Neglia, Karen S. Goon-Johnson, Steven S. Geier, Carlos G. Lee, Adrian P. Gee
Journal: Blood (1997)
The California Excise Tax on Cigarettes: The Tobacco Industry Profits From This Too
Authors: Deborah Parra-Medina
Journal: JAMA (1993)

<h3>To the Editor.</h3> —With the passage of the voter-initiated Proposition 99 in the fall of 1988, the California state excise tax on cigarettes was increased by 25 cents per package. The initiative earmarked the new revenues for tobacco use control, medical care, and research activities. Traditionally, excise taxes have been used primarily to produce revenues for federal and state governments. More recently, excise taxes have received recognition as policy-based measures with potential public health benefits. Since the initiation of the tax, California cigarette purchases have fallen at a rate of 1.7% per quarter,<sup>1</sup>and it is estimated that smoking prevalence has decreased 17%.<sup>2</sup>The California tax increase experience has strengthened the argument that the cigarette excise tax increases make good health policy because they precipitate a drop in tobacco purchasing. Evidence from California suggests that a 5% to 7% decline in consumption may be attributed to the 1989
Morphological and quantitative angiographic analyses of progression of coronary stenoses. A comparison of Q-wave and non-Q-wave myocardial infarction.
Authors: S Dacanay, H L Kennedy, E Uretz, J E Parrillo, L W Klein
Journal: Circulation (1994)

BACKGROUND The purpose of this study was to determine differences in coronary stenosis severity and morphology and time course of progression between Q-wave and non-Q-wave myocardial infarction (MI). METHODS AND RESULTS We studied 32 patients with new Q-wave MI and 38 patients with new non-Q-wave MI who underwent coronary angiography both before and after MI without interval revascularization procedures. Quantitative coronary angiographic analysis was performed by the caliper method, and morphological analysis of coronary angiograms was obtained before and soon after acute MI. Before infarction, the stenosis severity at the site of future MI was worse in Q-wave (44 +/- 25%) versus non-Q-wave (23 +/- 35%) MI patients (P &lt; .01). Eccentric and irregular plaques were more common in Q-wave MI patients (18 of 32, 56%, versus 5 of 38, 13%; P &lt; .001). Non-Q-wave MI patients were more frequently found to have significant collaterals after MI compared with Q-wave MI patients (18 of 38, 47%, versus 1 of 32, 3%; P &lt; .001) despite no difference in post-MI stenosis severity. Analysis according to time interval after pre-MI angiography showed that 9 of 11 patients (82%) with Q-wave MI &lt; 18 months later had a stenosis of &gt; or = 50% versus 7 of 21 (33%) with an interval &gt; 18 months (P &lt; .05). By comparison, non-Q-wave MI patients tended to fall into two categories regardless of time of progression: Either minimal or no stenosis (&lt; 20%) or else a severe stenosis (&gt; 70%) was typically present. CONCLUSIONS The atheromatous plaque substrate is different in Q-wave and non-Q-wave MI. Non-Q-wave MI occurs typically at a site shown by pre-MI angiography to involve either minimal luminal narrowing or a severe stenosis before MI, which is usually nonulcerated. By comparison, Q-wave MI follows a moderate stenosis in which the plaque is eccentric and ulcerated. Such differences culminate in differences in thrombus lability and collateral development and consequently in different clinical profiles.
1056 DELIVERY OF THE INTERFERON-γ SIGNALING MOIETY TO THE PDGFβ-RECEPTOR ON HEPATIC STELLATE CELLS AMELIORATES ESTABLISHED LIVER FIBROSIS IN MICE
Authors: R. Bansal, J. Prakash, M. de Ruiter, E. Post, L. Beljaars, K. Poelstra
Journal: Journal of Hepatology (2011)
Experimental models of torsade de pointes
Authors: L Eckardt
Journal: Cardiovascular Research (1998)

Torsade de pointes is a potentially life threatening form of polymorphic ventricular tachycardia typically seen in the setting of congenital and acquired abnormal QT-prolongation. Numerous in vitro studies have investigated basic ionic mechanisms underlying delayed repolarization. The role of different ion channels and the induction of early afterdepolarizations have been studied in various cardiac cells including M cells. In addition, isolated heart models with and without electrical stimulation and/or the use of drugs which prolong repolarization have been developed in recent years. Some of these models have simulated conditions likely to exist in the clinical setting of torsade de pointes, such as bradycardia and hypokalemia. In in vivo canine and rabbit models, torsade-like polymorphic ventricular tachyarrhythmias have been induced by the administration of different agents such as cesium, neurotoxins, e.g., anthopleurin or various class III drugs under conditions designed to mimic the clinical situation. In the context of recent advances in the molecular genetics of long QT syndrome, those models which have used sodium or potassium channel blockers have gained particular interest. Based on all experimental studies it seems probable that the first beats of torsade occur due to early afterdepolarizations and triggered activity. The development of subsequent beats is less clear. Reentry based on inhomogeneity of refractoriness has been suggested as the underlying mechanism.
EAU Guidelines on the Assessment of Non-neurogenic Male Lower Urinary Tract Symptoms including Benign Prostatic Obstruction
Authors: Christian Gratzke, Alexander Bachmann, Aurelien Descazeaud, Marcus J. Drake, Stephan Madersbacher, Charalampos Mamoulakis, Matthias Oelke, Kari A.O. Tikkinen, Stavros Gravas
Journal: European Urology (2015)
In vitro hydrodynamic comparison of mitral valve bioprostheses.
Authors: S Gabbay, D M McQueen, E L Yellin, R W Frater
Journal: Circulation (1979)

With the use of the pulse duplicator built in our laboratory, the hydrodynamic characteristics of three sizes of the four commercially available mitral bioprostheses, Hancock, Carpentier-Edwards, Angell-Shiley, and Ionescu-Shiley, were studied and compared. A wide range of performance was found: for example, during pulsatile testing, at peak flow of 15 1/min (corresonding to a normal resting cardiac output) transvalvular gradients varied from as high as 20 mm Hg (Angell-Shiley) to 5 mm Hg(Ionescu-Shiley) in the 25 mm mounting diameter size. Effective orifice areas (EOA) are significantly different in valves of the same mounting size, e.g., at peak flows of 20 1/min, the Ionescu-Shiley 25 provides an EOA of 1.7 cm2 while the Angell-Shiley provides only 1.17 cm2. The EOAs of all bioprostheses have been found to increase with increasing flow (e.g., from 10--30 1/min peak flow, the Hancock 25 changed from 1.25 cm2 to 1.50 cm2). The Gorlin formula, as constituted for calculating the area of stenotic mitral valves, is inappropriate for prosthetic valves. But the discharge coefficients of the bioprostheses have been found to be around 1 when the planimetered area of the open valve orifice is determined at a given flow. By using this discharge coefficient, the Gorlin formula will give an excellent estimate of the true orifice area of mitral bioprostheses.