tbuckley/cabot-search huggingface dataset:
Cytomegalovirus Antigen Expression, Endothelial Cell Proliferation, and Intimal Thickening in Rat Cardiac Allografts After Cytomegalovirus Infection
Authors: Karl Lemström, Petri Koskinen, Leena Krogerus, Mat Daemen, Cathrien Bruggeman, Pekka Häyry
Journal: Circulation (1995)

Background Cardiac allograft arteriosclerosis is the primary cause of late death in heart transplant recipients. Clinical studies have suggested that humoral and cellular immune response, hyperlipidemia, and cytomegalovirus (CMV) infection may amplify the disease. In this study, the role of CMV infection in the development of rat cardiac allograft arteriosclerosis is investigated. Methods and Results Heterotopic rat cardiac allografts were performed from the DA to the WF rat strains. To prevent rejection, the recipients received triple-drug (cyclosporine A 20 mg · kg −1 · d −1 , azathioprine 2 mg · kg −1 · d −1 , and methylprednisolone 0.5 mg · kg −1 · d −1 ) immunosuppression postoperatively. Recipient rats were infected intraperitoneally (n=21) with 10 5 plaque-forming units of rat CMV (RCMV) 1 day after transplantation or were left uninfected and used as controls (n=18). The grafts were removed 7 and 14 days and 1 and 3 months after transplantation. In 42% (9 of 21) of cardiac allografts in RCMV-infected rats, an intramural, mononuclear cell inflammation of small intramyocardial arterioles was observed compared with none in uninfected rats ( P =.005). Acute RCMV infection was associated with an early perivascular inflammatory cell response of helper T (W3/25), cytotoxic T (OX8), and NK (3.2.3) cells, macrophages (OX42), and major histocompatibility complex class II expression around small intramyocardial arterioles and capillaries. No upregulation of interleukin-2 receptor expression was seen. In arteries and small intramyocardial arterioles, RCMV infection was associated with a significant endothelial cell proliferation and a clear increase in intimal thickening. Significant endothelial cell proliferation was also observed in the capillaries after RCMV infection. Immunohistochemistry revealed specific focal RCMV early and late antigen expression in epicardial and interstitial ED1–immunoreactive mononuclear cell infiltrates and around small arterioles of RCMV-infected cardiac allografts. Occasionally, media cells of stenosed small intramyocardial arterioles also showed strong focal RCMV antigen expression. In addition, infectious RCMV could be recovered by plaque assay in cardiac allografts expressing RCMV antigens. Conclusions These results demonstrate a productive RCMV infection in cardiac allograft structures and suggest that RCMV infection accelerates cardiac allograft arteriosclerosis, particularly in small intramyocardial arterioles mediated by inflammatory responses in the vascular wall and perivascular space.
Health Policy and the Bureaucracy: Politics and Implementation
Authors: James D. Bentley
Journal: JAMA (1983)

In the past 50 years, the federal government has undertaken a dramatically expanded role in the health sector of our society. Many of its expanded initiatives have been based on relatively brief laws that set a broad policy direction but require extensive implementation actions by the executive branch or its designee. In<i>Health Policy and the Bureaucracy</i>, Frank Thompson examines the way the bureaucracy shapes and effects the program by the way it implements the underlying law. Thompson's objective is a worthy one. Historically, the politics of health legislation have received considerable attention; the politics of health policy implementation have received less systematic attention. In his initial chapter, Thompson establishes a reasonable theoretical framework for examining policy implementation. Unfortunately, he then attempts to describe the implementation of eight major health programs consisting of The Hill Burton hospital construction (15 pages), Health Planning and Resources Development (20 pages), Health Maintenance Organizations
Everything you know is wrong
Authors: T. Delamothe
Journal: BMJ (2008)

The hit of last year’s Christmas issue was Rachel Vreeman and Aaron Carroll’s demolition of medical myths, which garnered 21 A4 pages of media mentions within a month of publication. This year the same authors target myths with a seasonal flavour (doi:10.1136/bmj.a2769). A dispiriting message is that there are still no genuine hangover cures—other than to consume alcohol only in moderation or not at all. At this time of year, it may be a small consolation to know that you can mix alcohol with antibiotics (other than metronidazole), although most attenders at a London clinic still mistakenly believe that you shouldn’t (doi:10.1136/bmj.a2885).

The debunking of myths emerges as the …
EPINEPHRINE CONTENT OF THE SUPRARENAL GLANDS IN ANAPHYLAXIS
Authors: Maurice I. Smith, S. Ravitz
Journal: The Journal of Experimental Medicine (1920)

The epinephrine store of the suprarenal glands remains unaltered in guinea pigs and rabbits which have been sensitized to ox serum, or subjected to varying degrees of anaphylactic shock by the reinjection of the foreign protein.
Autologous peripheral blood stem cell transplantation of stem cells harvested in imatinib-induced complete cytogenetic remission: an example of in vivo purging in CML
Authors: P le Coutre, K A Kreuzer, G Massenkeil, G Baskaynak, P Zschieschang, I Genvresse, J Lupberger, M Mapara, B Dörken, R Arnold
Journal: Leukemia (2003)
Association Between Reduced Plasma 25-Hydroxy Vitamin D and Increased Risk of Cancer in Patients With Inflammatory Bowel Diseases
Authors: Ashwin N. Ananthakrishnan, Su–Chun Cheng, Tianxi Cai, Andrew Cagan, Vivian S. Gainer, Peter Szolovits, Stanley Y. Shaw, Susanne Churchill, Elizabeth W. Karlson, Shawn N. Murphy, Isaac Kohane, Katherine P. Liao
Journal: Clinical Gastroenterology and Hepatology (2013)
A Lecture on Scarlet Fever and its Prevention
Authors: G. Johnson
Journal: BMJ (1870)

GENTLEMEN,-There are few diseases which at the present time cause greater anxiety, suffering, and mortality, than scarlet fever.We hear of it and we meet with it everywhere-in public institutions and in private dwellings; in large towns, in small villages, and in isolated coun- try houses; in the cottage of the poor, in the parsonage and the palace -no class of life is exempt from the scourge.The immediate mor- tality from the disease, as shown by the returns of the Registrar-Gene- ral, is alarmingly high; but the deaths which result directly from the fever are probably less numerous than those which are indirectly, but not less certainly, due to the malady and its numerous secondary com- plications.Scarlet fever is a highly infectious disease.The symptoms are the result of a morbid poison, of whose nature we know nothing except what we learn by observing its operation upon the living body.During the progress of the disease the fever-poison is rapidly generated within the system and thrown off through various outlets into the surrounding air.This process of elimination, which, as regards the patient, is con- servative, and, in fact, forms an essential part of the process of cure, is dangerous to his associates and attendants.The poison retained within the system is a source of danger and often a cause of death to the pa- tient, while the poison thrown out of the body is injurious and destruc- tive to others.The case of two brothers now under my care in the Hospital affords a good illustration of both these propositions.A. C., aged 12, was living in a house where a girl had been suffer- ing from scarlet fever.On the 28th September, he had shivering head- ache and sore throat.He got up each day, but was unable to continue his work.On the ist October, he noticed that his skin was covered by a scarlet rash.Notwithstanding this, on the following day he went in a third-class carriage to Uxbridge, and shared the bed of his elder brother, who was a servant in a small farm-house.The day after A. C.'s arrival, his brother, B. C., complained of sore throat, and about the third day he had the scarlet eruption on his skin.Meanwhile, the first patient, A. C., was going out daily and doing some work on the farm, until on the 14th October, he noticed that his urine was highcoloured and scanty, and he had general dropsical swelling over the body.On the 20th October, he was admitted with the usual symptoms of acute renal dropsy, from which he is now rapidly recovering.His brother, who remained in bed during the first week of the fever, has had no renal or dropsical symptoms.When admitted on the 28th of October, he was suffering only from debility, and his skin was still freely scaling.
852 THE NF-κB SUBUNIT C-REL IS INVOLVED IN HEPATOCYTE PROLIFERATION IN CHRONIC INJURED AND REGENERATING LIVER
Authors: R.G. Gieling, A.M. Elsharkawy, D. Cowie, P. Raychaudhuri, J.H. Caamaño, F. Oakley, D.A. Mann
Journal: Journal of Hepatology (2009)
Overall health of Americans seems to be improving, report finds
Authors: M. McCarthy
Journal: BMJ (2013)

US citizens are smoking less and exercising more and do not seem to be getting any fatter, a new report concludes.

The report, America’s Health Rankings , annually assesses the health status of people in the United States by looking at 29 factors, such as rates of smoking, obesity, physical inactivity, preventable disease, premature death, and infant mortality but also social factors known to affect health, such as the proportion of children in poverty, rates of high school graduation, and access to care.1

The report is a joint effort of the United Health Foundation, a not for profit foundation established by the managed care provider UnitedHealth Group to improve healthcare, and which funded the project; …
Medication à la Newburg
Authors: A. B. Houston
Journal: JAMA (1967)

<h3>To the Editor:—</h3> In an article in your sister publication,<i>Archives of Internal Medicine</i>(<b>120</b>:85, 1967), I discovered in the summary on page 89 the following: We have reported a case of migratory eosinophilic pneumonia due to a sulfonamide given orally with a review of the literature. I hope that, to make it more palatable, it was given flavored.
Disruption of Axonal Transport by Loss of Huntingtin or Expression of Pathogenic PolyQ Proteins in Drosophila
Authors: Shermali Gunawardena, Lu-Shiun Her, Richard G. Brusch, Robert A. Laymon, Ingrid R. Niesman, Beth Gordesky-Gold, Louis Sintasath, Nancy M. Bonini, Lawrence S.B. Goldstein
Journal: Neuron (2003)
Feedback Regulation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase in Livers of Mice Treated with Mevinolin, a Competitive Inhibitor of the Reductase
Authors: Toru Kita, Michael S. Brown, Joseph L. Goldstein
Journal: Journal of Clinical Investigation (1980)

Compactin (ML-236B) and the related compound, mevinolin, are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase), the rate-controlling enzyme in cholesterol synthesis. Previous studies have shown that administration of compactin to cultured cells elicits a compensatory increase in the amount of HMG CoA reductase in the cells. A similar increase in HMG CoA reductase has been reported in livers of rats and mice that have been treated with compactin. In this study, we explore the mechanism for the mevinolin-mediated increase in hepatic HMG CoA reductase in mice that have been fed a control diet and a 2% cholesterol diet. Administration of mevinolin to mice on a control diet produced a 6- to 10-fold increase in the amount of HMG CoA reductase in liver microsomes. When mice were fed the cholesterol-enriched diet, cholesterol accumulated in the liver and HMG CoA reductase declined by 90%. The administration of mevinolin to cholesterol-fed mice produced a three to eightfold increase in HMG CoA reductase. Despite the abundant amount of cholesterol that was already present in the livers of the mevinolin-treated, cholesterol-fed animals, their elevated HMG CoA reductase could be rapidly suppressed by the subcutaneous injection of small amounts of mevalonate, the product of HMG CoA reductase. These data are compatible with the existence in mouse liver of a multivalent feedback regulatory mechanism for HMG CoA reductase in which suppression of the enzyme requires both a sterol and a nonsterol substance derived from mevalonate. By blocking mevalonate synthesis, mevinolin activates this regulatory mechanism, and this in turn causes an increase in hepatic HMG CoA reductase. The ability to suppress the elevated HMG CoA reductase with mevalonate may prove useful in potentiating the effectiveness of mevinolin as a hypocholesterolemic agent.
Abstract 1640: Unidentified genetic variants influence pancreatic cancer risk: An analysis of the PanScan genome-wide association study
Authors: Brandon L. Pierce, Lin Tong, Peter Kraft, Habibul Ahsan
Journal: Cancer Research (2012)

Abstract Genome-wide association (GWA) methods have been used to identify multiple pancreatic cancer susceptibility loci. However, it is likely that other unidentified common susceptibility variants exist. In this work we used data on 493,619 common autosomal single nucleotide polymorphisms (SNPs) from the PanScan GWA study (2,857 cases and 2,967 controls) to confirm the existence of unidentified susceptibility variants using two cross-validation methods: a polygenic risk score (PRS) approach and a power-replication approach. For the PRS approach, after excluding all SNPs from known pancreatic cancer susceptibility loci, we first constructed a polygenic risk models based on a training dataset and then tested the model in an independent testing dataset. The second approach (i.e., “power-replication) was based on calculating power to detect association for each SNP based on association estimates from a training set and then testing the power estimate for association with probability of replication in an independent testing data set. Using the polygenic risk score method, we demonstrate the existence of additional pancreatic cancer risk variants, the majority of which have P-values &amp;gt; 0.01 in the PanScan study. We also demonstrate enrichment for unidentified loci near gene regions. We reach similar conclusions using the power-replications approach, where SNPs with higher power to detect association were more likely to be replicated in an independent dataset at P&amp;lt;0.05, especially when analyses were restricted to SNPs in gene regions. While our results do not substantially improve pancreatic cancer prediction, they do provide further rationale for focusing association studies on genic regions and suggest that conducting larger GWA studies and innovative secondary analyses have the potential to reveal novel susceptibility loci. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1640. doi:1538-7445.AM2012-1640
Treatment of paediatric cholestasis due to canalicular transport defects: yet another step forward
Authors: Jose J G Marin, Roderick H J Houwen
Journal: Gut (2014)

Paediatric cholestasis is a rare but devastating group of diseases that usually manifest in infancy or childhood by impaired bile secretion, due to either primary or secondary alterations affecting the liver secretory machinery, and that may progress to cirrhosis and liver failure. Although there is resemblance in clinical symptoms, the cause of these diseases can be completely different, which is important because it determines, among others, the response to treatment. For a specific subgroup of cholestatic diseases, namely those associated with canalicular transport defects, our pathophysiological understanding has been increased enormously over the last decade. In parallel, treatment options have been developed,1 and the article by Gordo–Gilart et al 2 yet takes another step forward.

Several transport proteins located at the canalicular membrane of hepatocytes are required to maintain the correct secretory function of the liver (figure 1). A crucial role is played by a member of the superfamily of ATP-binding cassette proteins, the bile salt export pump ABCB11 (formerly designated as BSEP), which accounts for the active transport of bile acids into the canalicular lumen and, hence, the generation of the osmotic gradient that drives canalicular bile flow.3 The correct functioning of this and other transporters requires specific physical-chemical characteristics at the canalicular membrane, where they are inserted, which are dependent, in part, on …
Ramping up RANTES in the acute response to arterial injury
Authors: Timothy Hla, Myat Lin Oo
Journal: Journal of Clinical Investigation (2010)

Arterial injury results in the formation of neointimal lesions. Lack of resolution of the pathologic neointima leads to stenosis, tissue ischemia, and organ dysfunction. In this issue of the JCI, Kovacic et al. show that, in response to arterial injury in mice, the cytokine TNF-α triggers a novel signaling pathway involving the combinatorial action of two transcription factors, STAT3 and NF-κB (p65 subunit), in VSMCs (see the related article beginning on page 303). Upon activation, these factors turn on transcription of a potent T cell chemokine, RANTES, which selectively recruits T cells into the vessel wall as part of the vascular wound–healing response.
Ten-Year Results of a Comparison of Conservation with Mastectomy in the Treatment of Stage I and II Breast Cancer
Authors: Joan A. Jacobson, David N. Danforth, Kenneth H. Cowan, Teresa d'Angelo, Seth M. Steinberg, Lori Pierce, Marc E. Lippman, Allen S. Lichter, Eli Glatstein, Paul Okunieff
Journal: New England Journal of Medicine (1995)

Breast-conservation therapy for early-stage breast cancer is now an accepted treatment, but there is still controversy about its comparability with mastectomy. Between 1979 and 1987, the National Cancer Institute conducted a randomized, single-institution trial comparing lumpectomy, axillary dissection, and radiation with mastectomy and axillary dissection for stage I and II breast cancer. We update the results of that trial after a median potential follow-up of 10.1 years.
PHYSICAL DIAGNOSIS SERIES—THE EAR AND HEARING
Authors: George E. Shambaugh
Journal: JAMA (1961)

A brief description of ear anatomy introduces this reel. Physical signs relating to the external ear, tympanic membrane diseases, method of testing patency of the eustachian tube, deafness tests, facial nerve paralyses, and labyrinth tests are presented. Three patients demonstrating the effect of deafness on speech are shown.
Abstract 3312: Targeting Notch signaling to abrogate the increase in breast cancer stem cells induced by hypoxia
Authors: Sarah J. Conley, Elizabeth Gheordunescu, Rebecca Theisen, Max Wicha
Journal: Cancer Research (2012)

Abstract There is increasing evidence from our lab and others supporting the “cancer stem cell” hypothesis in breast cancer, which deems that tumors are driven a small population of cells exhibiting stem cell properties. These cancer stem/progenitor cells may also be responsible for mediating tumor metastasis and resistance to cancer treatments. Recently, several new cancer therapies targeting tumor angiogenesis have been developed and validated in clinical trials. However, clinical practice has revealed that these therapies ultimately result in drug resistance and do not prolong patient survival by more than a few months. It has been reported that these angiogenesis inhibitors promote tumor invasiveness and metastasis in rodent breast cancer models. We have used in vitro and in vivo assays to study the role of hypoxia in regulating mammary cancer stem cells. We have shown that breast tumor stem cell population increases in response to hypoxia in vitro and in tumors from anti-angiogenic treated mice. We hypothesize that this leads to increased tumor aggressiveness and may explain the resistance to these drugs seen in patients. In vivo, both sunitinib and bevacizumab treatment increased intratumoral hypoxia as well as the percentage of cells expressing ALDH as assessed by the Aldefluor assay in SUM-159 and MDA-MB-231 breast cancer xenografts in NOD/SCID mice. In addition, tumor cells obtained from sunitinib treated mice exhibit enhanced growth of secondary tumors in NOD/SCID mice, further supporting an increase in the tumor stem cell population. We also demonstrate that hypoxia (1-2% oxygen) enriches for stem cells by at least 2 fold in several breast cancer cell lines grown in vitro. Utilizing siRNA, we identified that HIF1a is required for the increased cancer stem cell population following hypoxia treatment. We next tested whether a gamma secretase inhibitor (GSI) can block hypoxia's ability to increase the cancer stem cell population since HIF1a is reported to activate the Notch signaling pathway, and this pathway is known to regulate stem cell self renewal. Treatment of cells with the GSI completely abrogated the increase in ALDH+ cells under hypoxic conditions. We are now testing the ability of GSIs to block the increase in CSCs seen in mice treated with anti-angiogenic drugs. This study may reveal that therapies targeting tumor angiogenesis should be combined with GSI treatments targeting the cancer stem cell population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3312. doi:1538-7445.AM2012-3312
Leptin secretion from adipose tissue in women. Relationship to plasma levels and gene expression.
Authors: F Lönnqvist, L Nordfors, M Jansson, A Thörne, M Schalling, P Arner
Journal: Journal of Clinical Investigation (1997)

The role of expression and secretion of the ob gene product, leptin, for the regulation of plasma leptin levels has been investigated in vitro using abdominal subcutaneous adipose tissue of 20 obese, otherwise healthy, and 11 nonobese women. Body mass index (BMI, mean+/-SEM; kg/m2) in the two groups was 41+/-2 and 23+/-1, respectively. Fat cell volume was 815+/-55 pl in the obese and 320+/-46 pl in the nonobese group. In the obese group, plasma leptin concentrations and adipose leptin mRNA (relative to gamma actin) were increased five and two times, respectively. Moreover, adipose tissue secretion rates per gram lipid weight or per fat cell number were also increased two and seven times, respectively, in the obese group. There were strong linear correlations (r = 0.6-0.8) between plasma leptin, leptin secretion, and leptin mRNA. All of these leptin measurements correlated strongly with BMI and fat cell volume (r = 0.7- 0.9). About 60% of the variation in plasma leptin could be attributed to variations in leptin secretion rate, BMI, or fat cell volume. We conclude that elevated circulating levels of leptin in obese women above all result from accelerated secretion rates of the peptide from adipose tissue because of increased ob gene expression. However, leptin mRNA, leptin secretion, and circulating leptin levels are all more closely related to the stored amount of lipids in the fat cells of adipose tissue than they are to an arbitrary division into obese versus nonobese.