tbuckley/cabot-search huggingface dataset:
Abnormalities of Hemorheological, Endothelial, and Platelet Function in Patients With Chronic Heart Failure in Sinus Rhythm
Authors: Christopher R. Gibbs, Andrew D. Blann, Robert D. S. Watson, Gregory Y. H. Lip
Journal: Circulation (2001)

Background —To investigate the hypothesis that abnormalities of hemorheological (fibrinogen, plasma viscosity), endothelial (von Willebrand factor [vWF]), and platelet (soluble P-selectin) function would exist in patients with chronic heart failure (CHF) who are in sinus rhythm, we conducted a cross-sectional study of 120 patients with stable CHF (median ejection fraction 30%). We also hypothesized that ACE inhibitors and β-blockers would beneficially affect the measured indices. Methods and Results —In the cross-sectional analysis, plasma viscosity ( P =0.001), fibrinogen ( P =0.02), vWF ( P &lt;0.0001), and soluble P-selectin ( P &lt;0.001) levels were elevated in patients with CHF compared with healthy controls. Women demonstrated greater abnormalities of hemorheological indices and vWF than males (all P &lt;0.05). Plasma viscosity ( P =0.009) and fibrinogen ( P =0.0014) levels were higher in patients with more severe symptoms (New York Heart Association [NYHA] class III–IV), but there was no relationship with left ventricular ejection fraction. When ACE inhibitors were introduced, there was a reduction in fibrinogen (repeated-measures ANOVA, P =0.016) and vWF ( P =0.006) levels compared with baseline. There were no significant changes in hemorheological, endothelial, or platelet markers after the introduction of β-blocker therapy, apart from a rise in mean platelet count ( P &lt;0.001). Conclusions —Abnormal levels of soluble P-selectin, vWF, and hemorheological indices may contribute to a hypercoagulable state in CHF, especially in female patients and in those with more severe NYHA class. Treatment with ACE inhibitors improved the prothrombotic state in CHF, whereas the addition of β-blockers did not. These positive effects of ACE inhibitors may offer an explanation for the observed reduction in ischemic events in clinical trials.
Skin Eruptions and Infected Wounds
Authors: D. Walsh
Journal: BMJ (1897)

I33 5 dermal layers, causing dcsquamation of unhealthy epidermis ;and reproduction of a new covering, as observed in ichthyosis, psoriasis, dry chronic eczema, and also in some cases of znyxoedema and cretinism.Among its general effects I have found that in doses of 15 gr.daily it causes a pulse-rate of 120 to 14oper minute, -which in different subjects may be either of high or low -tension.But thyroid extract seems also to rapidly exhaust latent cardiac energy, for if the dose be unduly increased, or if the patient is not fully accustomed to it, then the heart soon tires, and the pulse, although still quick, is weakened so as -to induce irritability, depression, and tendency to syncope.
Abstract 2001: GATA2: Potential role as a prostate cancer metastasis-driving gene
Authors: Yan Ting Chiang, Kendric Wang, Francesco Crea, Colin Collins, Peter Gout, Yuzhuo Wang
Journal: Cancer Research (2014)

Abstract Metastasis is thought to result from changes in the expression of specific metastasis-driving genes leading to a cascade of activated downstream genes that set the metastatic process in motion. The present study was aimed at identifying such metastasis-driving genes in prostate cancer for potential therapy and identification of primary prostate cancers that are likely to metastasize. To this end, a differential gene expression profile was established of metastatic LTL-313H and non-metastatic LTL-313B prostate cancer tissue xenografts, derived from one patient's specimen using sub-renal capsule grafting technology. The profile was then subjected to integrative analysis using the Ingenuity Upstream Regulator Analysis tool. Six candidate master regulatory genes were identified, including GATA2, a gene encoding a pioneer factor in prostate cancer. Elevated GATA2 expression in clinical metastatic prostate cancer tissues was found to correlate with poor patient prognosis. Furthermore, GATA2 gene silencing in human prostate cancer LNCaP cells led to a marked reduction in cell migration, tissue invasion, focal adhesion disassembly and to a drastic change in cell transcriptome. Furthermore, 582 genes were identified that are (i) differentially expressed after GATA2 gene silencing in LNCaP cells and (ii) whose changes in gene expression significantly correlated with changes in GATA2 expressions in a MSKCC prostate cancer patient cohort. Taken together, the data suggest that GATA2 could represent a prostate cancer metastasis-driving gene and that the expression patterns of GATA2 and its associated-genes could serve as signatures (biomarkers) for poor prognosis in prostate cancer. Citation Format: Yan Ting Chiang, Kendric Wang, Francesco Crea, Colin Collins, Peter Gout, Yuzhuo Wang. GATA2: Potential role as a prostate cancer metastasis-driving gene. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2001. doi:10.1158/1538-7445.AM2014-2001
Proteinuria, renal impairment, and death
Authors: Jeremy Levy
Journal: BMJ (2006)

If reducing proteinuria improves cardiovascular outcomes, urine dipstick testing will become crucial in hypertension 

I t has been known for many years that patients with chronic kidney disease have a significantly increased risk of cardiovascular morbidity and mortality. Many studies have shown that, in renal failure, increasing proteinuria and worse renal function are associated with more rapid progression and a higher incidence of cardiovascular events. Does the same hold true for patients with relatively minor degrees of renal impairment and low levels of proteinuria, even microalbuminuria? Is the combination especially important? And does this affect the management of patients?

First some technicalities. Proteinuria usually refers to protein that is detectable in urine with conventional urine dipsticks, and the amount of protein can vary from 300 mg to several grams a day. Proteinuria can be quantified reliably and easily by using spot urine protein: creatinine ratios, where normal is said to be < 20 mg/mmol (but see below). Just to confuse the issue, diabetologists have for many years measured albumin (rather than total protein) excretion in urine as an excretion rate (mg/day or μg/minute) and more recently as albumin: creatinine ratios. In patients with low levels of proteinuria the two results may be quite different since much of the urinary protein …
Lupus Nephritis and Other Autoimmune Features in Patients with Diabetes Mellitus Due to Autoantibody to Insulin Receptors
Authors: GEORGE C. TSOKOS
Journal: Annals of Internal Medicine (1985)

The frequency of various autoimmune features in 14 patients with insulin-resistant diabetes mellitus (type B) was reviewed. Twelve patients had leukopenia, high titers of antinuclear antibodies (speckled pattern), and hypoalbuminemia; 11 had elevated serum levels of IgG and high erythrocyte sedimentation rates; 7 had proteinuria and high serum levels of antibodies to DNA; and 5 had alopecia and elevated serum levels of IgA. Lupus erythematosus preparations were negative in all patients. Eight patients met the conventional criteria for the diagnosis of systemic lupus erythematosus. Three patients developed renal involvement while under care at the National Institutes of Health. Kidney tissue samples showed proliferative and membranous glomerulonephritis, tubulointerstitial nephritis, and electron-dense deposits similar to those of lupus nephritis. The lupus nephritis in these 3 patients appeared to be independent of the level of insulin-receptor antibody and glucose dysmetabolism. This study documents the presence of systemic lupus erythematosus in a large proportion of patients with insulin resistance due to autoantibodies to insulin receptors and emphasizes that careful monitoring of such patients for major complications of lupus nephritis is warranted.
332. Chronic Granulomatous Disease Gene Therapy Functionally Corrects the Phenotype of Polymorphonuclear Leukocytes (PMN)
Authors: Ulrich Siler, Marion G. Ott, Stefan Stein, Elke Karaus, Maja Rutishauser, Corinne Wenk, Dieter Hoelzer, Manuel Grez, Reinhard Seger
Journal: Molecular Therapy (2005)

The symptomatology of Chronic Granulomatous Disease (CGD) is primarily caused by the inability of PMN to produce reactive oxygen species and thereby to kill phagocytosed micro-organisms. The patients suffer from life-threatening bacterial and fungal infections with an overall mortality of 2|[ndash]|5% per year.In a gene therapy trial, G-CSF mobilized CD34+ cells from two gp91phox-/- CGD patients were transduced with a monocistronic gp91phox retroviral vector. The patients were treated with liposomal busulphan for two days and transduced cells were re-infused after the busulphan treatment. A significant fraction of gene marked cells was detected in peripheral blood of both patients since day +21. The aim of our study was to verify whether NADPH oxidase activity in gene marked peripheral blood cells was therapeutically relevant.
DNA methylation and differentiation.
Authors: L A Michalowsky, P A Jones
Journal: Environmental Health Perspectives (1989)

The methylation of specific cytosine residues in DNA has been implicated in regulating gene expression and facilitating functional specialization of cellular phenotypes. Generally, the demethylation of certain CpG sites correlates with transcriptional activation of genes. 5-Azacytidine is an inhibitor of DNA methylation and has been widely used as a potent activator of suppressed genetic information. Treatment of cells with 5-azacytidine results in profound phenotypic alterations. The drug-induced hypomethylation of DNA apparently perturbs DNA-protein interactions that may consequently alter transcriptional activity and cell determination. The inhibitory effect of cytosine methylation may be exerted via altered DNA-protein interactions specifically or may be transduced by a change in the conformation of chromatin. Recent studies have demonstrated that cytosine methylation also plays a central role in parental imprinting, which in turn determines the differential expression of maternal and paternal genomes during embryogenesis. In other words, methylation is the mechanism whereby the embryo retains memory of the gametic origin of each component of genetic information. A memory of this type would probably persist during DNA replication and cell division as methylation patterns are stable and heritable.
Screening for Alcoholism
Authors: J. Paul Seale
Journal: JAMA (1988)

<h3>To the Editor.—</h3> I read with interest the recent article by Drs Cyr and Wartman<sup>1</sup>regarding the use of screening questions for the detection of alcoholism in ambulatory care. Studies such as these are greatly needed, as most existing instruments for alcohol screening are too lengthy to be used in the course of a routine office interview. In addition, the validity of other instruments in the outpatient setting is uncertain, as most were developed using male inpatients with advanced alcoholism as index cases. The methods used in this study, however, raise concerns in two areas. To begin with, of the patients screened, 52% were unemployed, raising the question of how transferable the results of this study would be to a practice setting in which most patients are employed. Second, the results of the study were based on an "alcoholic" population identified using a cutoff score of 5 on the
Genomic response to interferon-α in chimpanzees: Implications of rapid downregulation for hepatitis C kinetics
Authors: Robert E. Lanford, Bernadette Guerra, Helen Lee, Deborah Chavez, Kathleen M. Brasky, Catherine B. Bigger
Journal: Hepatology (2006)

The mechanism of the interferon-alpha (IFN-alpha)-induced antiviral response during hepatitis C virus (HCV) therapy is n o t completely understood. In this study,we examined the transcriptional response to IFN-alpha in uninfected chimpanzees after single doses of chimpanzee, human, or human-pegylated IFN-alpha. Liver and peripheral blood mononuclear cell (PBMC) samples were used for total genome microarray analysis. Most induced genes achieved maximal response within 4 hours, began to decline by 8 hours, and were at baseline levels by 24 hours postinoculation, a time when high levels of circulating pegylated IFN-alpha were still present. The rapid downregulation of the IFN-alpha response may be involved in the transition between the observed phase I and phase II viral kinetics during IFN-alpha therapy in HCV-infected patients. The response to all three forms of IFN-alpha was similar; thus, the reasons for previous failures in antiviral treatment of chimpanzees with human IFN-alpha were not due to species specificity of IFN-alpha. The response to IFN-alpha was partially tissue-specific. A total of 1778 genes were altered in expression by twofold or more by IFN-alpha, with 538 and 950 being unique to the liver or PBMC, respectively. Analysis of the IFN-alpha and IFN-gamma responses in primary chimpanzee and human hepatocytes were compared as well. IFN-alpha and IFN-gamma induced partially overlapping sets of genes in hepatocytes. In conclusion, the response to IFN-alpha is largely tissue-specific, and the response is rapidly downregulated in vivo, which may have a significant influence on the kinetics of antiviral response.
Congenital Dermal Sinus Associated with Meningitis
Authors: B. S. Cardell, B. Laurance
Journal: BMJ (1951)

A congenital dermal sinus communicating with the central nervous system or its coverings is one of the less common routes by which a pathogenic organism may gain access to the meninges and produce a meningitis.Because early recognition is important and simple opera- tive excision is available as an efficient prophylactic measure against such infection, a fatal case of con- genital dermal sinus associated with meningitis is reported here.Thirty-four cases of this malformation have been recorded in the literature, and -their essential features, together with those of the present case, are summarized in Table I.The lesion consists of an epithelial tube ex- tending inwards from the skin of the midline of the back to connect with the central nervous system or its cover- ings.Not uncommonly the sinus opening is associated with a tuft of hair, an area of pigmentation, or a capillary haemangioma.The sinus is lined by epidermis and there may or may not be dermal structures in the wall.The inner end of the sinus is often expanded to form a dermoid or an epidermoid cyst.Histologically it is identical with the common pilonidal sinus which occurs in the sacro-coccygeal region, and has no communica- tion with the spinal cord or the meninges (Rogers and Dwight, 1938).It differs from the pilonidal sinus in its location, having been recorded in all sites between the occiput and the sacro-coccygeal region (see Table II), TABLE II.-Congenital Derinal Sinuses: Site Cranial (occiput) 2 Lumbar .. .10 Cervical .. . 1 Sacral ...12* Thoracic . . .9 Sacro-coccygeal 1 * Including the present case.and in its connexion with the central nervous system or the meninges.As Walker and Bucy (1934) point out, the term pilonidal sinus is a rrisnomer, since hair is often not present in these sinuses; they suggest that congenital dermal sinus is a more accurate descriptive name for all these malformations.TABLE I.-Recorded Cases of Congenital Dermal Sinuts Communicating with the Central Nervous System or Meninges
Oesophageal cancer in Britain.
Authors: J. Powell, W. H. Allum
Journal: BMJ (1992)

and, frequently, by severe symptoms.Their uncertainty is not alleviated by prolonged investigations that delay palliation and generally fail to answer their questions about the origin of the tumour and the prognosis.Patients deserve prompt palliation, appropriate investigation, and adequate support and counselling through what is too often a terminal illness.
Spontaneous sustained ventricular tachycardia in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial
Authors: Kelley P. Anderson, Richard Walker, Ted Dustman, Marc Fuller, Motomi Mori
Journal: Journal of the American College of Cardiology (1995)

Objectives. We compared the QRS waveforms of the initial and subsequent complexes of spontaneous sustained monomorphic ventricular tachycardia and the rhythm induced at electrophysiologic study to test the theory that premature ventricular complexes "trigger" spontaneous ventricular tachycardia and that a stable substrate exists such that the spontaneous arrhythmia can be reproduced at electrophysiologic study. Background. Failure rates have been high in several recent studies in which prevention of ventricular tachyarrhythmias was guided by suppression of premature ventricular complexes or induced ventricular tachycardias. Methods. Digital waveform analysis was used to distinguish events of ventricular tachycardia initiated by configurationally distinct, possibly triggering, complexes (type 1) from events in which the initial QRS waveforms were identical to subsequent complexes, suggesting no requirement for premature ventricular beats (type 2). Results. Of 1,102 episodes of spontaneous ventricular tachycardia, 73 (6.6%) were type 1; 1,012 were type 2 (91.8%); and 17 (1.5%) were uncertain. Of 59 patients only 14 (24%) had only type 1 episodes (group 1), whereas 37 patients (63%) had predominantly type 2 events (group 2) (p < 0.0001). Sustained ventricular tachycardia was inducible in all group 1 patients, and in most (57%) the induced rhythm was similar to the spontaneous rhythm. Ventricular tachycardia could not be induced in 7 patients from group 2 (19%), and in 18 patients (49%) the induced and spontaneous rhythms were dissimilar. Recurrence of arrhythmia rates differed according to the guidance method in group 2. Conclusions. Discrepancies between observed and predicted modes of initiation of ventricular tachycardia and between spontaneous and induced rhythms could result in inappropriate guidance and subsequent failure of antiarrhythmic treatment.
Points: A better way to detect growth failure
Authors: E C Coles
Journal: BMJ (1987)

SIR,-On 1 December Dr Ribeiro, a general practitioner in South Africa, and his wife were shot dead in their home by armed men in disguise.Dr Ribeiro was well known in South Africa for his work on the torture of children by the South African police and army.Earlier this year Dr Ribeiro and his family had a miraculous escape after their home was attacked and destroyed by arsonists.The letter by a group of doctors
Pathway discovery in mantle cell lymphoma by integrated analysis of high-resolution gene expression and copy number profiling
Authors: Elena M. Hartmann, Elias Campo, George Wright, Georg Lenz, Itziar Salaverria, Pedro Jares, Wenming Xiao, Rita M. Braziel, Lisa M. Rimsza, Wing-Chung Chan, Dennis D. Weisenburger, Jan Delabie, Elaine S. Jaffe, Randy D. Gascoyne, Sandeep S. Dave, Hans-Konrad Mueller-Hermelink, Louis M. Staudt, German Ott, Sílvia Beà, Andreas Rosenwald
Journal: Blood (2010)
Differential effects of sorafenib on liver versus tumor fibrosis mediated by stromal-derived factor 1 alpha/C-X-C receptor type 4 axis and myeloid differentiation antigen-positive myeloid cell infiltration in mice
Authors: Yunching Chen, Yuhui Huang, Thomas Reiberger, Annique M. Duyverman, Peigen Huang, Rekha Samuel, Lotte Hiddingh, Sylvie Roberge, Christina Koppel, Gregory Y. Lauwers, Andrew X. Zhu, Rakesh K. Jain, Dan G. Duda
Journal: Hepatology (2013)

Sorafenib--a broad kinase inhibitor--is a standard therapy for advanced hepatocellular carcinoma (HCC) and has been shown to exert antifibrotic effects in liver cirrhosis, a precursor of HCC. However, the effects of sorafenib on tumor desmoplasia--and its consequences on treatment resistance--remain unknown. We demonstrate that sorafenib has differential effects on tumor fibrosis versus liver fibrosis in orthotopic models of HCC in mice. Sorafenib intensifies tumor hypoxia, which increases stromal-derived factor 1 alpha (SDF-1α) expression in cancer and stromal cells and, subsequently, myeloid differentiation antigen-positive (Gr-1(+)) myeloid cell infiltration. The SDF-1α/C-X-C receptor type 4 (CXCR4) pathway directly promotes hepatic stellate cell (HSC) differentiation and activation through the mitogen-activated protein kinase pathway. This is consistent with the association between SDF-1α expression with fibrotic septa in cirrhotic liver tissues as well as with desmoplastic regions of human HCC samples. We demonstrate that after treatment with sorafenib, SDF-1α increased the survival of HSCs and their alpha-smooth muscle actin and collagen I expression, thus increasing tumor fibrosis. Finally, we show that Gr-1(+) myeloid cells mediate HSC differentiation and activation in a paracrine manner. CXCR4 inhibition, using AMD3100 in combination with sorafenib treatment, prevents the increase in tumor fibrosis--despite persistently elevated hypoxia--in part by reducing Gr-1(+) myeloid cell infiltration and inhibits HCC growth. Similarly, antibody blockade of Gr-1 reduces tumor fibrosis and inhibits HCC growth when combined with sorafenib treatment.
Prognostic significance of nonfatal reinfarction during 3-year follow-up: Results of the thrombolysis in myocardial infarction (TIMI) phase II clinical trial
Authors: Hiltrud S. Mueller, Sandra A. Forman, Mark A. Menegus, Lawrence S. Cohen, Genell L. Knatterud, Eugene Braunwald
Journal: Journal of the American College of Cardiology (1995)