tbuckley/cabot-search huggingface dataset:
Myocardial Lesions Produced by Digitalis in the Presence of Hyperthyroidism: An Experimental Study
Authors: WILLIAM H. DEARING, ARLIE R. BARNES, HIRAM E. ESSEX
Journal: Circulation (1950)

Calculated therapeutic doses of digitalis and its derivatives did not produce demonstrable microscopic changes in the myocardium of experimental animals. Toxic doses of digitalis (twice a therapeutic dose) induced myocardial lesions in animals. In those animals with experimentally induced mild to moderate hyperthyroidism, calculated therapeutic doses of digitalis did produce myocardial lesions. Toxic doses of digitalis administered to animals with mild to moderate hyperthyroidism caused extensive degenerative changes in the myocardium or promptly killed the animals without associated microscopic lesions.
Doctors must read drug labels, not whinge about them
Authors: J A W Wildsmith
Journal: BMJ (2002)

EDITOR—Twice last year the BMJ gave column space to doctors reporting confusion between ampoules of water, saline, and lignocaine (also called lidocaine) for injection. 1 2 These doctors blame the similarity in ampoule shape and colour rather than admitting to the fundamental problem of having simply failed to read the label.

In my view, the differences between the …
Polymorphic genomic fingerprinting of synchronous hepatocellular cancers identified by arbitrarily primed-polymerase chain reaction (AP-PCR)
Authors: Y Sirivatanauksorn, V Sirivatanauksorn, S Bhattacharya, K. Savage, J Rees, AP Dhillon, NR Lemoine, RCN Williamson, BR Davidson
Journal: Journal of Hepatology (1998)
Abstract 3199: p53 represses TRF2 through E3 ubiquitin ligase Siah-1: Feedback regulation in telomere-initiated damage signaling
Authors: Izumi Horikawa, Kaori Fujita, Abdul M. Mondal, Borivoj Vojtesek, Jean-Christophe Bourdon, David P. Lane, Curtis C. Harris
Journal: Cancer Research (2010)

Abstract p53 plays critical roles in tumor suppression, stem cell functions and aging in vivo. The telomere-capping protein complex (shelterin) prevents functional telomeres from undergoing erosion or end-to-end fusion and from initiating unwanted DNA damage response. Uncapped, dysfunctional telomeres at the end of cellular replicative lifespan lose this protective mechanism and trigger telomere-initiated DNA damage signaling to activate p53 and thereby induce cellular senescence. Here we report that p53 in turn controls a component of the shelterin complex, TRF2, through Siah-1, a p53-inducible E3 ubiquitin ligase. Endogenous TRF2 and Siah-1 were repressed and induced, respectively, in normal human fibroblasts at replicative senescence, when p53 was physiologically activated. Spontaneous allelic loss, shRNA-mediated knockdown, dominant-negative inhibition, nutlin-3a activation and overexpression of p53 all showed that p53 induced Siah-1 and repressed TRF2. TRF2 was subject to proteasomal degradation in a p53-dependent manner. Anti-TRF2 antibody-immunoprecipitated proteins were found to undergo p53- and Siah-1-mediated ubiquitination. In vitro and in vivo ubiquitination experiments showed that the E3 ligase activity of Siah-1 was responsible for TRF2 ubiquitination. Biologically, Siah-1 knockdown or TRF2 overexpression delayed the onset of replicative senescence, suggesting that the proteolytic control of TRF2 cooperates with the transcriptional regulation of p53 target genes (e.g., p21WAF1 and microRNA-34a) to regulate p53-mediated replicative senescence. This study reveals that p53, which is a downstream effector of the DNA damage signaling from uncapped telomeres, also functions upstream to regulate the telomere-capping complex, and suggests that the p53-Siah-1-TRF2 pathway takes an integral part in orchestrating the DNA damage response at telomeres. Given that TRF2 inhibits a p53-activating kinase ATM at telomeres, a positive feedback loop involving TRF2, ATM and p53 may function to amplify DNA damage-induced and p53-mediated cellular responses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3199.
A new technique for examining intestinal biopsies
Authors: B. L. Chapman, K. Henry, F. Paice, J. S. Stewart, N. F. Coghill
Journal: Gut (1973)

A new technique for measuring changes in the architecture of the small intestinal mucosa is described using a modification of the technique of television image analysis to measure the areas occupied by the surface and crypt epithelium in proximal jejunal biopsies. The ratios of these two areas to each other were then calculated. In 12 control mucosae, the mean ratio (±SD) was 2·27 ± 0·41. In 12 untreated flat mucosae, by contrast, the mean ratio was only 0·24 ± 0·07. This ten-fold difference, which was highly significant (p &lt; 0·001), was greater than that for any similar measurements previously reported. This technique is intended for the measurement of changes in the mucosa too small for existing techniques to detect reliably rather than for the diagnosis of coeliac disease.
Increased Expression of Interleukin-1 in Coronary Artery Disease With Downregulatory Effects of HMG-CoA Reductase Inhibitors
Authors: Torgun Wæhre, Arne Yndestad, Camilla Smith, Terje Haug, Siv Haugen Tunheim, Lars Gullestad, Stig S. Frøland, Anne G. Semb, Pål Aukrust, Jan K. Damås
Journal: Circulation (2004)

Inflammation is important in atherogenesis. Interleukin (IL)-1 is the prototypic inflammatory cytokine. We hypothesized a dysbalance between inflammatory and anti-inflammatory mediators in the IL-1 family in coronary artery disease (CAD) and a possible modulation of these mediators by HMG-CoA inhibitors (statins).In a microarray screening experiment examining peripheral blood mononuclear cells (PBMCs) from 6 CAD patients and 4 healthy control subjects, IL-1beta was identified as 1 of 25 genes whose expression were upregulated in CAD and downregulated by statins. In the following, we studied the role of IL-1beta and related mediators in CAD. Our major findings were as follows. (1) Although mRNA levels of IL-1alpha and IL-1beta were markedly reduced in PBMCs from CAD patients after 6 months of simvastatin (20 mg/d, n=15) and atorvastatin (80 mg/d, n=15) therapy, the reduction in IL-1 receptor antagonist (IL-1Ra) was more modest. Statins also reduced the spontaneous release of IL-1beta and IL-1Ra from PBMCs in CAD patients. (2) mRNA levels of IL-1alpha, IL-1beta, and IL-1Ra were increased in PBMCs from patients with stable (n=20) and unstable (n=20) angina compared with healthy control subjects (n=15). Although the unstable patients had particularly high levels of IL-1beta and IL-1alpha, IL-1Ra was not correspondingly increased. (3) IL-1beta induced release of proatherogenic cytokines from PBMCs, whereas atorvastatin partly abolished this effect.Our findings suggest that cytokines in the IL-1 family may represent therapeutic targets in CAD. The ability of statins to modulate these cytokines in an anti-inflammatory direction underscores their immunomodulatory potential.
Amino acid sequence of EC2 domain in CD81 is highly conserved in Japanese subjects
Authors: Nobuyuki Ito, Sumio Kawata, Shinji Tamura, Hiromu Nakajima, Shinichi Kiso, Ayuko Saeki, Takanori Oue, Toshiaki Hanafusa, Yuji Matsuzawa
Journal: Hepatology (2000)

Chronic hepatitis C virus (HCV) infection is a serious issue that leads to liver cirrhosis and hepatocellular carcinoma and is widely distributed throughout Western countries and the Far East.Over a million people are infected with HCV in Japan.The mechanism by which HCV infects host cells remains unknown.Binding of viral glycoproteins to cell surface molecules is a key to viral infectivity.Recently, Pileri et al. 1 found that human CD81 (or TAPA-1), a member of the tetraspan family, binds to HCV glycoprotein E2.CD81 spans the cell surface lipid bilayer 4 times forming 2 extracellular loops EC1 and EC2.CD81 is highly conserved across species, except for many differences in EC2 between humans and other species (interspecies variable region, Fig. 1); only a single difference in this region has been detected between humans and chimpanzees, the only permissive hosts for HCV infection.Thus, the EC2 domain may play a key role in HCV infectivity.We postulated that a polymorphism in this region confers resistance against HCV infection.We amplified the DNA spanning exons 6 to 8 of CD81 by polymerase chain reaction (PCR) using genomic DNA as a template for direct sequencing of the interspecies variable region (Fig. 1).DNA was extracted from peripheral blood of 86 healthy volunteers (43 men, 43 women, with normal liver function and who were HCV antibody [Ab] negative), 20 patients with chronic HCV infection (12 men, 8 women, who were HCV-Ab and -RNA positive; with sustained abnormal liver function in all but 3), and 2 subjects with normal liver function who were HCV-Ab positive but HCV-RNA negative.All subjects were Japanese.All PCR products showed a single band at approximately 900 bp on ethidium bromide-stained gels.Sequencing of PCR products showed a nucleotide substitution C 596 =T
Funding grant proposals for scientific research: retrospective analysis of scores by members of grant review panel
Authors: N. Graves, A. G. Barnett, P. Clarke
Journal: BMJ (2011)

<b>Objective</b> To quantify randomness and cost when choosing health and medical research projects for funding. <b>Design</b> Retrospective analysis. <b>Setting</b> Grant review panels of the National Health and Medical Research Council of Australia. <b>Participants</b> Panel members' scores for grant proposals submitted in 2009. <b>Main outcome measures</b> The proportion of grant proposals that were always, sometimes, and never funded after accounting for random variability arising from differences in panel members' scores, and the cost effectiveness of different size assessment panels. <b>Results</b> 59% of 620 funded grants were sometimes not funded when random variability was taken into account. Only 9% (n=255) of grant proposals were always funded, 61% (n=1662) never funded, and 29% (n=788) sometimes funded. The extra cost per grant effectively funded from the most effective system was $A18 541 (£11 848; €13 482; $19 343). <b>Conclusions</b> Allocating funding for scientific research in health and medicine is costly and somewhat random. There are many useful research questions to be addressed that could improve current processes.
Lp(a) Lipoprotein as a Risk Factor for Myocardial Infarction
Authors: George G. Rhoads, Gosta Dahlen, Kare Berg, Newton E. Morton, Andrew L. Dannenberg
Journal: JAMA (1986)

The Lp(a) lipoprotein is structurally related to low-density lipoprotein but is found in lower plasma concentration. It has been associated with coronary disease in several white populations. To test the generalizability of this association, we measured serum Lp(a) by quantitative immunoelectrophoresis in 303 Hawaiian men of Japanese ancestry with a prior myocardial infarction (MI) and in 408 population-based controls. Mean values were 17.1 and 13.7 mg/dL (0.171 and 0.137 g/L), respectively. Increased risk for MI was shown mainly for men in the upper quartile of the Lp(a) lipoprotein distribution (greater than or equal to 20.1 mg/dL [greater than or equal to 0.201 g/L]). Odds ratios at younger than 60, 60 to 69, and 70 years of age or older were 2.5, 1.6, and 1.2 times those for men in the lower three quartiles, respectively. In a multiple logistic model the association with MI remained significant and was not explained by differences in total cholesterol levels, high-density lipoprotein or low-density lipoprotein cholesterol levels, subscapular skin fold, systolic blood pressure, history of smoking, alcohol consumption, or age. We conclude that Lp(a) is an important attribute that should often be considered when coronary heart disease risk is assessed.
QUANTITATIVE DISTRIBUTION OF PARTICULATE MATERIAL (MANGANESE DIOXIDE) ADMINISTERED INTRAVENOUSLY TO THE CAT
Authors: Cecil K. Drinker, Louis A. Shaw
Journal: The Journal of Experimental Medicine (1921)

1. Manganese dioxide suspended in an acacia-sodium chloride solution provides a non-toxic injection which in the present experiments has contained no particles larger than 1µ and which, when deposited in the body, can be determined quantitatively and seen microscopically. 2. Intravenous injections have been made under precautions which preclude removal from the blood or deposition in organs through simple capillary blockage. 3. In nine experiments out of thirteen the circulating blood contained no manganese after 18 minutes. In the four remaining instances there was a steady slight elimination which was incomplete at the end of 1 hour. Within certain limits the rate of removal from the circulating blood and the sites of deposition in the animal are not influenced by the concentration of the suspension, the blood pressure, or antecedent introduction of acacia or histamine. 4. In the cat amounts of manganese dioxide varying between 9.8 and 3.9 mg. of manganese and containing from 50,000,000,000 to 10,000,000,000 particles, if injected intravenously, permit recovery at the end of 1 hour of 90 per cent of the material in the lungs, liver, and spleen in the following proportions: lungs 47 per cent; liver 38.3 per cent; spleen 4.3 per cent. 5. These experiments, coupled with correlative results by other investigators, make it clear that in certain organs—the lungs, liver, and spleen of the cat—the vascular endothelium possesses phagocytic power rendering the capillaries permeable to particulate material as well as to gases, liquids, and dissolved substances.
Vertigo Following Air Travel
Authors: Burton F. Jaffe
Journal: New England Journal of Medicine (1979)

IN an airplane passenger who had episodes of delayed vertigo after flight, the probable pathologic course leading to a perilymph fistula in the inner ear is described. Operation on the fistula allowed her to resume flying without such episodes.Case ReportIn November, 1972, a 35-year-old woman who had an upper respiratory infection but who had previously been healthy flew on an airplane for three hours. After landing, she experienced dizziness and nausea. After the return trip, she had vertigo and a "crackling sound" in the left ear. Ear-nose-throat and neurologic examinations and audiologic, electronystagmographic, ear-polytomographic, and blood tests gave . . .
Life, Death, and AIDS
Authors: Robert L. Cohen
Journal: Annals of Internal Medicine (1999)

Letters20 July 1999Life, Death, and AIDSRobert L. Cohen, MDRobert L. Cohen, MDNew York, NY 10014 (Cohen)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-2-199907200-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest and sympathy the plea of Drs. Selwyn and Arnold to avoid a mechanistic approach to the care of persons with AIDS as potentially effective therapy becomes available (1). Their memories of the earlier days of this epidemic reminded me of my own experience. I served as the vice president for medical operations of the New York City Health and Hospitals Corporation from 1986 through 1988.The most powerful memories I retain are of leading physicians, deans, and department chairs urging me to remove patients with AIDS from the public hospitals staffed by New ...Reference1. Selwyn PA, Arnold R. From fate to tragedy: the changing meanings of life, death, and AIDS. Ann Intern Med. 1998;129:899-902. LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Robert L. Cohen, MDAffiliations: New York, NY 10014 (Cohen) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byContributions That Mitigated the Epidemic 20 July 1999Volume 131, Issue 2Page: 158KeywordsAIDSGraduate medical educationMemory ePublished: 15 August 2000 Issue Published: 20 July 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Staphylococcus aureus cell envelope antigen is a new candidate for the induction of IgA nephropathy
Authors: Akio Koyama, Samina Sharmin, Hideko Sakurai, Yoshio Shimizu, Kouichi Hirayama, Joichi Usui, Michio Nagata, Keigyou Yoh, Kunihiro Yamagata, Kaori Muro, Masaki Kobayashi, Kaori Ohtani, Takeshi Shimizu, Tohru Shimizu
Journal: Kidney International (2004)
Isolation and properties of myocardial prostaglandin synthetase
Authors: C. J. LIMAS, J. N. COHN
Journal: Cardiovascular Research (1973)

The microsomal fraction prepared from canine myocardium was found to contain an active prostaglandin synthetase (average, 10 mμ mol PGE2/mg protein/min) which was capable of forming PGE2 from arachidonic acid in the presence of reduced glutathione and cofactors such as l-adrenaline, hydroquinone, and p-aminophenol. Neither aspirin nor phospholipase A, which have been reported to affect prostaglandin synthesis in other tissues, influences the activity of myocardial prostaglandin synthetase.
Immunohistochemical analysis of HLA (A, B, C) antigens in liver disease using a monoclonal antibody.
Authors: C Barbatis, J Woods, J A Morton, K A Fleming, A McMichael, J O McGee
Journal: Gut (1981)

The distribution of HLA class I antigens was studied in 42 liver biopsies and eight necropsies by an immunoperoxidase technique employing a monoclonal antibody which reacts with the heavy chains of class I (A, B, C) HLA antigens. In normal liver HLA class I antigens could not be detected on hepatocyte cell membranes or cytoplasm; these antigens were present on the cell membrane of bile duct epithelium, on sinusoidal lining cells, fibroblasts, and blood vessel endothelium. However, in all patients with acute alcoholic hepatitis, most cases of primary biliary cirrhosis and some cases of chronic active hepatitis HLA class I antigens were detectable focally or diffusely on the cell membrane of hepatocytes; in two cases of acute viral hepatitis (non-A, non-B) HLA class I antigens were present in granular form in the cytoplasm of all hepatocytes. These findings may be relevant to the prolonged survival of liver allografts in man and other species and in the pathogenesis of some liver diseases.
The Effect of Preoperative MRI on Mastectomy Rates in Breast Cancer Patients.
Authors: E. Cobain, S. Hong, H. Abe, S. Jansen, N. Jaskowiak, G. Newstead, O. Olopade
Journal: Cancer Research (2009)

Abstract Background: Currently, there are two primary surgical options for the treatment of early stage breast cancer: modified radical mastectomy and breast conserving surgery (BCS) with post-surgical radiation. Numerous studies have shown that there is no survival difference between the two surgical treatments, however, in recent years, there is data to suggest that mastectomy rates have been on the rise. While many factors undoubtedly influence surgical management decisions in breast cancer patients, the effect of routine use of preoperative breast MRI may be a contributor to the rise in mastectomy rates. Methods: Breast cancer patients who were treated surgically and received a preoperative MRI were identified using a database from the University of Chicago Department of Radiology, which contains information on over 4200 patients who have received breast MRI since 2002. These patients were cross-referenced with data from the University of Chicago Cancer Registry, which contains information regarding type of surgical treatment, surgeon, stage of cancer at time of diagnosis and surgical stage for all breast cancer patients treated at the University of Chicago Hospitals from 2000-2007. Annual mastectomy rates from 2000-2007 were calculated and compared using Pearson's Chi Square test. Annual mastectomy rates were stratified by mean age at diagnosis and stage of disease. Mastectomy rates prior to routine use of preoperative MRI (2000-2002) and after routine use of preoperative MRI (2005-2007) were calculated for breast cancer patients under 45 and over 45 years of age and rates were compared using Fisher's exact test. Results: A total of 1,404 patients received surgical treatment for a new diagnosis of breast cancer between 2000 and 2007 at the University of Chicago Hospitals. Results to date indicate that mastectomy rates across all years are not significantly different (p = 0.315). Results also indicate that the mean age at diagnosis of patients who receive mastectomy as the initial surgical treatment for their breast cancer is higher than those who receive BCS from 2000-2002, but is lower than those who receive BCS from 2003-2007. In addition, breast cancer patients under the age of 45 have higher rates of mastectomy since the routine use of preoperative MRI which trends toward statistical significance (p = 0.0598). Conclusion: These preliminary results indicate that overall mastectomy rates at the University of Chicago Hospitals are not increasing in concordance with the increased use of preoperative MRI testing, but that younger breast cancer patients may have higher rates of mastectomy in the MRI era. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4019.
PMO-048 Reduction in pro-inflammatory cytokines after weight loss surgery: a prospective study
Authors: A Belgaumkar, K Carswell, R Mitry, R Hughes, A Dhawan, A Patel
Journal: Gut (2012)

<h3>Introduction</h3> Morbid obesity is associated with a pro-inflammatory state, reflected by a relative increase in levels of pro-inflammatory cytokines and corresponding decrease in anti-inflammatory cytokines. The production of active mediators by the adipose tissue plays an important role in this pathological state. We aimed to study the effects of laparoscopic sleeve gastrectomy (LSG) on markers of oxidative stress, inflammatory mediators interleukin (IL) 6 and IL-10, and the adipocytokines Resistin, Leptin and Adiponectin. <h3>Methods</h3> We prospectively studied 19 patients (13 females, mean age 45 years; range 27–64) who underwent LSG at our institution. Fasting bloodsamples were taken pre-operatively and at 6 months post surgery. Fasting blood glucose, serum insulin and lipids were also measured at the same time points. IL-6, IL10, Adiponectin, Leptin and Resistin were measured using a bead-based multiplex bioassay. HOMA-IR was used as a measure of insulin resistance. Markers of oxidative stress—lipid peroxidation (TBARS) and glutathione peroxidase (GPX)—were measured using commercially available biochemical kits. Results are expressed as mean. Statistical analysis employed one-way ANOVA with repeated measures. <h3>Results</h3> LSG was associated with significant weight loss (pre-op 60.0±2.59 kg/m2, vs 53.0±2.35 at 6 weeks, 45.8±2.0 at 6 months, p&lt;0.0001). Insulin resistance decreased significantly (HOMA-IR 8.7±1.4 vs 3.8±0.7 vs 2.4±0.5, p&lt;0.0001). IL-6 and Leptin levels were significantly lower at 6 months post-op (6.6±1.0 pg/ml vs 4.8±1.1, p&lt;0.031; 16.4±3.1 ng/ml vs 5.3±1.2, p&lt;000.1). Resistin, Adiponectin and IL-10 levels did not change significantly: Resistin 1.0±0.1 ng/ml vs 0.97±0.1; Adiponectin 11.7±1.8 μg/ml vs 9.9±1.5; IL-10 pg/ml 0.72±0.1 vs 0.67±0.1. There were no significant changes in TBARS or GPX. <h3>Conclusion</h3> Insulin resistance and BMI fall significantly after LSG and this is accompanied by a fall in pro-inflammatory cytokines, IL-6 and Leptin. There was no concomitant rise in anti-inflammatory IL-10 and adiponectin. Markers of oxidative stress did not change significantly. Restrictive surgery results in improvements in insulin resistance and a significant reduction in weight. The resulting reduction in adipose tissue, with changes in production of the adipocytokines, has a complex effect on the inflammatory milieu and requires further elucidation. <h3>Competing interests</h3> None declared.