tbuckley/cabot-search huggingface dataset:
Plasma Monocyte Chemoattractant Protein-1 and Pulmonary Vascular Resistance in Chronic Thromboembolic Pulmonary Hypertension
Authors: HIROSHI KIMURA, OSAMU OKADA, NOBUHIRO TANABE, YOSHIHIRO TANAKA, MASARU TERAI, YUICHI TAKIGUCHI, MASAHISA MASUDA, NOBUYUKI NAKAJIMA, KENZO HIROSHIMA, HIDEKUNI INADERA, KOUJI MATSUSHIMA, TAKAYUKI KURIYAMA
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The pathogenesis of severe pulmonary hypertension seems to be related to inflammatory response in diseased sites. Monocyte chemoattractant protein-1 (MCP-1) has been reported to play a role in the development of congestive heart failure. In this immunological response, activation and migration of leukocytes including macrophages to the inflammatory region are important factors. We hypothesized that the severity of pulmonary hypertension may be related to MCP-1, which is thought to be upregulated by blood pressure or shear stress in pulmonary vasculature as well as by immunological and inflammatory reactions in chronic thromboembolic pulmonary hypertension (CTEPH). Circulating levels of MCP-1, interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) were measured by sandwich ELISA in 14 patients with CTEPH. The plasma level of MCP-1 was significantly correlated with pulmonary vascular resistance. In IL-1beta and TNF-alpha, on the other hand, there was no correlation between cytokines and pulmonary hemodynamics. Pathological specimens obtained from the patients with CTEPH undergoing thromboendarterectomy demonstrated immunoreactivity of MCP-1 in endothelium, smooth muscle cells, and macrophages within neointima in the hypertensive large elastic pulmonary artery. We conclude that MCP-1 is upregulated in the remodeling of pulmonary arteries in close association with increased pulmonary vascular resistance in CTEPH.
Treatment of Acne
Authors: David A. Voron
Journal: JAMA (1981)

To the Editor.—  In their article, Topical Agents Alone in Acne: A Blind Assessment Study (243:1640, 1980), Swinyer and associates state,  degree of surface dryness or brittleness in our study is the single variable significantly associated with failure to clear acne lesions (Table 2). However, Table 2 actually indicates that patients with severe skin dryness showed more improvement than those with moderate skin dryness.  The authors assert that their thesis regarding the usefulness of water avoidance in the treatment of acne is supported by their finding that a program of tretinoin, benzoyl peroxide, and water avoidance was as effective as a combination treatment of tretinoin and systemically given tetracycline. Since benzoyl peroxide (which is both an effective antiacne agent and extremely drying) was part of the water avoidance regimen, but not included in the non-water-avoidance regimen, this assertion is unjustified.  Thus, the data presented by these authors do not
Transcriptional Repression of Gata3 Is Essential for Early B Cell Commitment
Authors: Anupam Banerjee, Daniel Northrup, Hanane Boukarabila, Sten Erik W. Jacobsen, David Allman
Journal: Immunity (2013)

The mechanisms underlying the silencing of alternative fate potentials in very early B cell precursors remain unclear. Using gain- and loss-of-function approaches together with a synthetic Zinc-finger polypeptide (6ZFP) engineered to prevent transcription factor binding to a defined cis element, we show that the transcription factor EBF1 promotes B cell lineage commitment by directly repressing expression of the T-cell-lineage-requisite Gata3 gene. Ebf1-deficient lymphoid progenitors exhibited increased T cell lineage potential and elevated Gata3 transcript expression, whereas enforced EBF1 expression inhibited T cell differentiation and caused rapid loss of Gata3 mRNA. Notably, 6ZFP-mediated perturbation of EBF1 binding to a Gata3 regulatory region restored Gata3 expression, abrogated EBF1-driven suppression of T cell differentiation, and prevented B cell differentiation via a GATA3-dependent mechanism. Furthermore, EBF1 binding to Gata3 regulatory sites induced repressive histone modifications across this region. These data identify a transcriptional circuit critical for B cell lineage commitment.
Abstract LB-316: The landscape of actionable genomic lesions in small cell bladder cancer
Authors: Matthew T. Chang, Saurabh Asthana, Gopakumar Iyer, Neil Desai, Hikmat Al-Ahmadie, Jocelyn Chapman, Bernard H. Bochner, Jonathan E. Rosenberg, Dean F. Bajorin, David B. Solit, Barry S. Taylor
Journal: Cancer Research (2014)

Abstract Small cell cancers are aggressive tumors with unfavorable prognosis. Small cell bladder carcinomas are a particularly troublesome and poorly differentiated tumor where little is known and in which few targeted therapeutic options exist for molecularly defined patients. We therefore sought to characterize both common and actionable aberrant pathways in small cell bladder tumors to serve as a guide for therapeutic development. Utilizing a combination of deep targeted capture and whole-genome sequencing approaches, we characterized the mutational and DNA copy number alteration spectrum of twenty patients with small-cell bladder cancer including multi-region profiling of a subset of cases with mixed small cell and urothelial histologies. Integrating molecular, clinical, and pathway data along with comparative genomic analyses of 371 urothelial bladder and small cell lung cancers, we identified histology- and lineage-specific lesions and significant differences in the prevalence of specific pathway aberrations. Whole-genome sequencing revealed structurally complex tumors and, in some cases, somatic hypermutation, including one sample harboring more than 150,000 clonal mutations. Aberrations in G1/S cell cycle progression appear to be pathognomonic in small cell tumors. Furthermore, additional lesions affecting both pro/anti apoptotic as well as metabolic pathways occurred in patterns that are distinct from other small-cell and bladder cancers. In total, 85% of small cell bladder cancer samples contain at least one potentially clinically actionable lesion. These results indicate that integrative genomic analyses of small-cell bladder cancer facilitates therapeutic development and pathway targeting in a complex mutational landscape. Citation Format: Matthew T. Chang, Saurabh Asthana, Gopakumar Iyer, Neil Desai, Hikmat Al-Ahmadie, Jocelyn Chapman, Bernard H. Bochner, Jonathan E. Rosenberg, Dean F. Bajorin, David B. Solit, Barry S. Taylor. The landscape of actionable genomic lesions in small cell bladder cancer. [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 LB-316. doi:10.1158/1538-7445.AM2014-LB-316
420. Hydrodynamic Limb Vein Delivery of Naked IGF-1 Plasmid DNA Provides Therapeutic Benefit in SOD1(G93A) Murine ALS Model
Authors: Gyula Acsadi, Roumen Anguelov, Xingli Li, Mary Kay Bates, Jon A. Wolff, Hans Herweijer
Journal: Molecular Therapy (2006)

Motor neuron degeneration and death in ALS can be mitigated by neurotrophic factors. A number of neurotrophic factors (e.g., VEGF, GDNF and IGF-1) have been demonstrated to promote survival and regeneration of motor neurons both in vitro and in vivo. An increase in the lifespan of SOD1 mice was observed following delivery of viral vectors expressing GDNF or IGF-1. For human gene therapy, a non-viral approach would be preferred. Recently, highly effective transfer of plasmid DNA expression vector to skeletal muscle was described using hydrodynamic delivery of pDNA solutions into limb veins. This method promises a safe non-viral gene therapy route that is equally effective in small and large research animals. Here we determined if IGF-1 expression vectors delivered by the hydrodynamic limb procedure can alter the clinical course of disease in SOD1(G93A) mice. An expression vector was generated in which the human IGF-1 cDNA was under transcriptional control of the human CMV promoter. The plasmid DNA was injected into 6- week old SOD1 mice (prior to the onset of disease symptoms) in both hind limbs. For the plasmid DNA deliveries, the hind limbs were temporarily isolated by the placement of a tourniquet. The plasmid DNA solution (1.0 ml) was subsequently delivered into the saphenous vein at a rate of 0.17 ml/sec. The tourniquet was released after 2 minutes. SOD1 mice treated with IGF-1 lived 28 days longer (138 ± 4.5 days) than untreated SOD1 mice (110.1 ± 5.2 days). This improvement in survival was equal if not better than after adeno- associated virus vector IGF1 gene transfer. IGF-1 and reporter gene expression was detected from injected muscles but not in the sera or spinal cords at end-point of the experiments. The motor performance (RotaRod) declined less rapidly in the IGF-1 injected SOD1 mice than in the controls. These data suggest that hydrodynamic limb vein plasmid DNA transfer of IGF-1 had a beneficial therapeutic effect for SOD1 mice. It is most likely that this effect was due to target-derived functions of IGF-1 originating from muscle expression (i.e., retrograde transport of IGF-1 protein from the site of production in the muscle tissue to the motor neuron body). This technique has promise for treatment of ALS.
Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long-term treatment with levamisole in children
Authors: F Rongioletti, L Ghio, F Ginevri, D Bleidl, S Rinaldi, A Edefonti, C Gambini, G Rizzoni, A Rebora
Journal: British Journal of Dermatology (1999)

Journal Article Purpura of the ears: a distinctive vasculopathy with circulating autoantibodies complicating long‐term treatment with levamisole in children Get access F Rongioletti, F Rongioletti DISEM, Section of Dermatology, University of Genoa, Italy, Search for other works by this author on: Oxford Academic Google Scholar L Ghio, L Ghio Division of Nephrology, Paediatric Clinic, Milan, Italy, Search for other works by this author on: Oxford Academic Google Scholar F Ginevri, F Ginevri Division of Nephrology, Search for other works by this author on: Oxford Academic Google Scholar D Bleidl, D Bleidl Dermatology, Search for other works by this author on: Oxford Academic Google Scholar S Rinaldi, S Rinaldi Division of Nephrology, Bambin Gesù Hospital, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar A Edefonti, A Edefonti Division of Nephrology, Bambin Gesù Hospital, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar C Gambini, C Gambini Pathology, Gaslini Institute, Genoa, Italy, Search for other works by this author on: Oxford Academic Google Scholar G Rizzoni, G Rizzoni Division of Nephrology, Bambin Gesù Hospital, Rome, Italy Search for other works by this author on: Oxford Academic Google Scholar A Rebora A Rebora DISEM, Section of Dermatology, University of Genoa, Italy, Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 140, Issue 5, 1 May 1999, Pages 948–951, https://doi.org/10.1046/j.1365-2133.1999.02833.x Published: 01 May 1999
Abdominal Pain, Intermittent Hydronephrosis, and Accessory Renal Vessels
Authors: Anthony F. Lalli
Journal: JAMA (1967)

THE DIFFERENTIAL diagnosis of the patient with vague upper abdominal pain apparently arising in the right upper quadrant includes the standard considerations such as cholecystitis, ulcer disease, and functional bowel distress. This last diagnosis was made in several of the patients whose cases are reported here and who later proved to have intermittent hydronephrosis caused by accessory renal vessels. Unless specific questions are put regarding the periodicity of the pain and its relationship to maintained positions of the body and/or the ingestion of large quantities of fluid, the correct diagnosis may not be suspected. When the diagnosis is considered and an excretory urogram is performed in the absence of the pain, the hydronephrosis may not be demonstrated.<sup>1,2</sup>The necessity of performing the urogram during an attack of pain is emphasized herein. The data on nine young adults with this syndrome observed during the past ten years at the University
Asthma after childhood pneumonia: six year follow up study
Authors: C. E Clark
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To establish the long term cumulative prevalenceof asthma in children admitted to hospital with pneumonia and to examine the hypothesis that some children admitted to hospital with pneumonia may be presenting with undiagnosed asthma. <b>Design:</b> Prospective study of a cohort of children previously admitted to hospital with pneumonia, followed up by postal questionnaires totheir general practitioners and the children or their parents. <b>Setting:</b> General practices in southwest England. <b>Participants:</b> 78 children admitted to the Royal Devon and Exeter Hospital between 1989 and 1991 with a diagnosis of pneumonia confirmed on independent review of <i>x</i> ray films. <b>Main outcome measures:</b> Any diagnosis of asthma, use of any treatment for asthma, and asthma symptom scores. <b>Results:</b> On the basis of a 100% response rate from general practitioners and 86% from patients or parents, the cumulative prevalence of asthma was 45%. A diagnosis of asthma was associated with a family history of asthma (odds ratio 11.23; 95% confidence interval 2.57 to 56.36; P=0.0002). Mean symptom scores were higher for all children with asthma (mean score 2.4; χ<sup>2</sup>=14.88; P=0.0001)and for children with asthma not being treated (mean 1.4; χ<sup>2</sup>=6.2; P=0.01)than for those without asthma (mean 0.2) <b>Conclusions:</b> A considerable proportion of children presenting to a district general hospital with pneumonia either already have unrecognised asthma or subsequently develop asthma. The high cumulative prevalence of asthma suggests that careful follow up of such children is worth while. Asthma is undertreated in these children; a structured symptom questionnaire may help to identify and reduce morbidity due to undertreatment.
Polypoid Barrett’s High-Grade Dysplasia in a Patient with Familial Adenomatous Polyposis: a Unique Association
Authors: H. Wolfsen
Journal: Endoscopy (2005)

Figure 1 A 30-year-old white man with familial adenomatous polyposis (FAP) was referred for evaluation of Barrett’s esophagus with high-grade dysplasia, an association not previously reported. Diagnosed during adolescence with FAP, he had undergone proctocolectomy in 1996. Subsequently, screening endoscopy for duodenal polyps detected long-segment Barrett’s glandular mucosa replacing most of the esophageal mucosa (14 cm segment length), with polypoid changes. Similar-appearing polyps were noted throughout the stomach and duodenum.
Dobson defends use of the PFI for hospital building
Authors: A. Ferriman
Journal: BMJ (1999)

The health secretary, Frank Dobson, last week defended the use of private rather than public money to fund his department's hospital building programme on the grounds that it got hospitals built faster and allowed capital that would have been spent on hospitals to be spent on other projects, such as replacing old, outdated equipment.

He maintained that if there were any difference in cost between building a hospital with money from the private finance initiative (PFI) and building one with Treasury money, it was marginal. He also claimed that the use of the PFI was not the reason why new hospitals were being built with fewer beds than before.

Mr Dobson was being questioned by MPs from the health select committee about Department of Health expenditure. He said: “A lot of the talk about the private finance initiative gives the impression that the high cost of building a …
P621Bone morphogenetic protein 7 protects against pressure overload-induced left ventricular remodeling and facilitates its regression in mice
Authors: D Merino, AV Villar, JF Nistal, MA Hurle
Journal: Cardiovascular Research (2014)

Purpose: TGF-β1 and 2 exert fibrogenic and hypertrophic effects in the myocardium under biomechanical stress. Another member of the TGF-β family, Bone Morphogenetic Protein 7 (BMP7), opposes TGF-β-induced fibrogenesis. Herein, we assessed the role of BMP7 in the LV remodeling response to pressure overload and in the LV reverse remodeling after pressure overload release.
NTAL phosphorylation is a common event in the signaling pathways initiated by antigen and stem cell factor (SCF) in mast cells
Authors: S. Iwaki, C. Tkaczyk, A.B. Satterthwaite, P. Draber, V. Horejsi, D.D. Metcalfe, A.M. Gilfillan
Journal: Journal of Allergy and Clinical Immunology (2004)
Size of the Major Epicardial Coronary Arteries at Necropsy
Authors: Sigmund L. Wilens
Journal: JAMA (1966)

Measurements at necropsy on 401 men indicate that variations in the original, presclerotic size of large epicardial coronary arteries may play a significant role in vulnerability to myocardial infarction and suggest that angiographic measurements of these vessels during life might detect susceptible individuals. Infarcts are seldom found in hearts with large coronary arteries (more than 7 sq cm external surface area per 100 gm heart weight) but are common when these arteries are small (less than 6 sq cm/100 gm). They are, in fact, seven times as frequent in the latter groups as in the former. Unlike large elastic arteries, the coronaries do not enlarge with advancing age. They increase only slightly in size in hypertrophied hearts and do not shrink in size in atrophic ones.
Capillary filtration coefficient: the technique and its application to the small intestine
Authors: P. D. I. RICHARDSON, D. N. GRANGER, A. E. TAYLOR
Journal: Cardiovascular Research (1979)

In this review, we discuss the physiological basis of the capillary filtration coefficient (Kf,c), and its measurement in the small intestine. First the various techniques by which Kf,ccan be measured are discussed and assessed; the second part of the review considers the volumetric method of determining Kf,c in more detail, in an attempt to identify the causes of variability in published values for intestinal Kf,c. Finally, we discuss changes in intestinal Kf,c due to sympathetic nerve stimulation and the administration of drugs and hormones. The majority of estimates of intestinal Kf,c are about 0.38 to 0.60 (innervated) to 0.60 to 0.75 (denervated) cm3·min−1·kPa−1·100g−1. These values are increased by most vasodilator drugs and hormones, and decreased by sympathetic nerve stimulation and by vasoconstrictor drugs.
Reintroduction of medical officers of health would solve many problems
Authors: J F Soothill
Journal: BMJ (1997)

Editor—As the son of the secretary of the Society of Medical Officers of Health who successfully defended that splendid Victorian Liberal office against the Baldwin government (Dr V F Soothill), I write to express enthusiasm for Dr Lewis Moonie and Mr Sam Galbraith's proposal that medical officers of health should be reintroduced.1 It is strange that Dr Moonie and Mr Galbraith are Labour …
The House of Medicine
Authors: C. A. Hoffman
Journal: JAMA (1972)

This is the House of Medicine. Shall it be a House united, or a House divided? That, in my judgment, is the central question before us at this moment in our history. Shall we as a profession continue to speak, through this House of Medicine, with one, strong, effective voice, or shall we succumb to the festering factionalism that can only serve to diminish that voice? That is the choice we face, that is the decision we must make. Factionalism in our profession springs from a number of causes and assumes a number of forms. First, let us examine some of the causes. The state of mind of most physicians today is one of profound disquiet growing out of the threat we feel each day to our profession. Almost daily, there are new infringements on the way we practice—intrusions by government and by other third parties. Almost daily, there are
Hyperkalaemic cardiac arrhythmia caused by potassium citrate mixture.
Authors: J J Browning, K S Channer
Journal: BMJ (1981)

was treated with frusemide 80 mg daily and isosorbide dinitrate 10 mg four times daily.Later he developed a chest infection and episodes of supra- ventricular tachycardia, which were suppressed with verapamil 80 mg three times a day.He was symptom free 14 days after admission, the radiographic signs of left heart failure had resolved, and he was mobilised.Five days later gross bilateral ankle oedema was noted.Jugular venous pressure was normal and the chest x-ray film and electrocardiogram were unchanged.Frusemide and verapamil were continued in the same dosage and isosorbide withdrawn.The ankle oedema resolved within 48 hours without accompanying weight loss.Isosorbide was reintroduced when he was fully ambulant: the oedema did not recur.Case 3-A 61-year-old man with ischaemic heart disease and congestive cardiac failure was admitted for reassessment.He had basal crepitations, raised jugular venous pressure, enlargement of the liver, and bilateral ankle oedema.An electrocardiogram showed atrial fibrillation and previous anterior myocardial infarction.There was radiographic evidence of cardio- megaly and pulmonary venous congestion.Liver function tests were abnormal.Serum albumin, urea, and creatinine concentrations were normal.Treatment with digoxin, bumetanide, spironolactone, and isosorbide dinitrate 20 mg three times a day was continued.He was not confined to bed.Weight and ankle circumference were measured serially.Isosorbide was withdrawn after seven days.Over the next week, while symptoms and weight were unchanged, the ankle oedema decreased.Isosorbide was reintro- duced.The oedema reaccumulated over the following week and his weight remained unchanged.
Sarcoidosis and multiple myeloma: an association.
Authors: T Pettersson, E Koivunen, M Ilvonen, J Jouppila, E Aalto, C Wasastjerna
Journal: BMJ (1987)

Sarcoidosis and multiple myeloma: an associationAn association between sarcoidosis and neoplasia has been suggested.The development of malignant lymphoma has been reported in several patients with sarcoidosis,2 but there have been few reports of patients with sarcoidosis and multiple myeloma.24We describe five patients with sarcoidosis who developed multiple myeloma. Case historiesThe table shows details offive patients with sarcoidosis seen by us during 1%9- 86.In each case the diagnosis ofsarcoidosis was based on both the clinical findings and histological evidence ofnon-caseating epithelioid cell granulomas.The mean age of the patients at the time of diagnosis was 55 (range 42-65).In four patients myeloma developed several years after the diagnosis of sarcoidosis; in one both diagnoses were made at the same time.The duration ofsarcoidosis was more than two years in three patients (cases 1, 2, and 4), and sarcoidosis was considered to be active at the time of diagnosis of myeloma in two (cases 2 and 5).Two patients (cases 1 and 2) had been treated with steroids.All patients met the diagnostic criteria for multiple myeloma.Four patients (cases 1-4) were treated with cytotoxic drugs and the other (case 5) was followed up without treatment.Four patients survived, but the other (case 3) died in 1985, four years after the diagnosis of myeloma.
Hospitals will be able to earn 49% of their income from private patients from October
Authors: Z. Kmietowicz
Journal: BMJ (2012)

NHS hospitals in England will be able to increase the proportion of money they earn from private patients to 49% from 1 October, the Department of Health has announced.

The change to how much money foundation trusts can earn from non-NHS work was introduced in the Health and Social Care Act.1 The original bill had said that there was nothing to stop a foundation trust from making all its money from private patients. But during its passage through the House of Lords peers voted in an amendment that said that most of …