tbuckley/cabot-search huggingface dataset:
Lack of Cardiac Manifestations among Patients with Previously Treated Lyme Disease
Authors: Oliver Sangha, Charlotte B. Phillips, Kirsten E. Fleischmann, Thomas J. Wang, Anne H. Fossel, Robert Lew, Matthew H. Liang, Nancy A. Shadick
Journal: Annals of Internal Medicine (1998)

Background: Cardiac involvement is common in acute Lyme disease, and case reports suggest that cardiac abnormalities might also occur years after the primary infection. Objective: To determine the prevalence of cardiac abnormalities in persons with previously treated Lyme disease. Design: Population-based, retrospective cohort study with controls. Setting: Nantucket Island, Massachusetts. Participants: From among 3703 adult respondents to a total-population (n = 6046) mail survey, 336 (176 case-patients and 160 controls) were randomly selected for clinical evaluation. Measurements: Current cardiac symptoms and major or minor abnormal electrocardiographic features, including heart rate; rhythm; axis; PR, QRS, and QT intervals; QRS structure; atrioventricular blocks; and ST-segment and T-wave changes. Results: Persons with Lyme disease (case-patients, n = 176) (mean duration from disease onset to study evaluation, 5.2 years) and persons without evidence of previous Lyme disease (controls, n = 160) did not differ significantly in their patterns of current cardiac symptoms and electrocardiographic findings, including heart rate (P > 0.2), PR interval (P = 0.15), QRS interval (P > 0.2), QT interval (P > 0.2), axis (P > 0.2), presence of arrhythmias (P > 0.2), first-degree heart block (P = 0.12), bundle-branch block (P > 0.2), and ST-segment abnormalities (P > 0.2). In multivariate analyses that adjusted for age, sex, and previous heart disease, a history of previously treated Lyme disease was not associated with either major (odds ratio, 0.78; P > 0.2) or minor (odds ratio, 1.09; P > 0.2) electrocardiographic abnormalities. Conclusion: Persons with a history of previously treated Lyme disease do not have a higher prevalence of cardiac abnormalities than persons without a history of Lyme disease.
Office Laboratory Series
Authors: Lois Addison
Journal: JAMA (1985)

Until very recently the physician's office laboratory was a neglected aspect of outpatient medical care. The laboratory frequently consisted only of an old microscope tucked away in an unused corner of the office. Few tests were performed. Tests were often done by untrained staff. "Quality control" was an unrecognized term and seemed to be an unnecessary concern. Test charges were low and frequently were not passed on to the patient. Those days are over. Office laboratories now perform half of all outpatient clinical laboratory procedures. A quiet technological revolution has made a wide spectrum of tests available to office laboratories, many of which a few years ago could be done only in specialized research settings. As a result of this revolution, office laboratory equipment manufacturers are now recognized as the financial growth leaders of the entire health care industry. Recent financial incentives have helped to promote the transfer of laboratory
Abstract IA08: Targeting histone methylation in leukemia
Authors: Scott A. Armstrong
Journal: Cancer Research (2013)

Abstract Leukemias harboring rearrangements of the MLL gene carry a poor prognosis. Over the past 6 years, it has become increasingly clear that fusions of MLL induce widespread epigenetic deregulation that may mediate much of their transforming activity. The histone methyltransferase DOT1L, which methylates histone 3 on lysine 79 (H3K79), has received particular attention. Genome-wide H3K79 methylation profiles in MLL-rearranged leukemias are abnormal, and can serve to distinguish MLL-rearranged from other types of leukemias. Loss of H3K79 methylation affects expression of MLL-target loci and is detrimental to the leukemogenic activity of MLL-rearranged cells, suggesting that a DOT1L dependent, aberrant epigenetic program drives transformation in these leukemias. Small molecule DOT1L inhibitors have been developed and selectively inhibit proliferation of MLL-rearranged leukemia cells. These molecules are now in clinical trials for patients with relapsed refractory leukemia. Also, the Polycomb Repressive Complex 2 (PRC2) has been implicated in self-renewal and cancer progression, and its components are overexpressed in many cancers, but its role in cancer development and progression remains unclear. We have used conditional alleles for the PRC2 components Enhancer of Zeste 2 (Ezh2) and Embryonic Ectoderm Development (Eed) to characterize the role of PRC2 function in leukemia development and progression. Compared to wildtype leukemia, Ezh2-null MLL-AF9-mediated acute myeloid leukemia (AML) show decreased organ infiltration and failed to accelerate upon secondary transplantation. However, Ezh2-null leukemias maintained self-renewal up to the third round of transplantation, indicating that Ezh2 is not strictly required for MLL-AF9 AML. In contrast, inactivation of the essential PRC2 gene, Eed led to complete ablation of PRC2-function, which is incompatible with leukemia growth. Gene expression array analyses indicated more profound gene expression changes in Eed-null compared to Ezh2-null leukemic cells, including downregulation of Myc target genes and upregulation of PRC2 targets. These data show that histone-modifying enzymes play critical roles in leukemia and may be relevant therapeutic targets in these diseases. Citation Format: Scott A. Armstrong. Targeting histone methylation in leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Jun 19-22, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2013;73(13 Suppl):Abstract nr IA08.
Quantitative studies on plasmalemmal folds and caveolae of rabbit ventricular myocardial cells.
Authors: K R Levin, E Page
Journal: Circulation Research (1980)

Plasmalemmal folds and caveolae were investigated by qualitative and quantitative analysis of electron micrographs obtained by freeze fracture and transmission electron microscopy (TEM) of rabbit right ventricular papillary muscles whose mean sarcomere lengths ranged from 1.64 to 2.28 micron. In passively extended muscles, folds were observed at sarcomere lengths of 2.3 micron and could be shown by extrapolation to become completely extended at a maximum sarcomere length of 2.8 micron. It was concluded that the plasmalemma does not contribute to resting tension in the physiological range of sarcomere lengths. Caveolae are present in both the external plasmalemmal envelope and T-tubular plasmalemma. They show no preferential distribution with respect to underlying myofibrillar striations or membrane folds and are nearly devoid of membrane particles in freeze-fractured material. The surface density of caveolar necks (4.0/micron2 apparent plasmalemmal area) is only 16-20% of that reported for frog skeletal muscle. Caveolae augment plasmalemmal area by 21-32%, assuming two or three caveolae per neck, respectively. Caveolar membrane does not serve as a reservoir of membrane to be recruited into external plasmalemma, at least over the physiological range of sarcomere lengths. In heart muscle they do not account for the T-tubular access resistance, and their function in this tissue remains unknown.
Assessment of variceal pressure by continuous non-invasive endoscopic registration: a placebo controlled evaluation of the effect of terlipressin and octreotide.
Authors: F Nevens, W Van Steenbergen, S H Yap, J Fevery
Journal: Gut (1996)

Octreotide has been proposed for the treatment of variceal bleeding. The effects on portal pressure, however, have been variable in published studies. As bleeding is more directly related to pressure in the varices, this study investigated the effect on variceal pressure of octreotide and terlipressin, a vasoactive drug with a well established effect. Variceal pressure was measured during four to eight minutes by a continuous non-invasive endoscopic registration method. Thirty patients in whom a stable variceal pressure recording had been obtained during at least one minute, were randomised to receive either 2 mg terlipressin, 50 micrograms octreotide or an identical volume of saline, as a single intravenous injection given over 60 seconds. For the final analysis three patients had to be excluded because of lack of a satisfactory recording. There were no significant clinical differences between the three groups of patients. Placebo administration did not induce significant changes, but a mean decrease in variceal pressure of -27% was noted with terlipressin, starting from two minutes onwards. Variceal pressure changes after injection of octreotide were variable and the mean change in pressure did not reach statistical significance. Seven of 10 patients showed a temporary increase in variceal pressure. In conclusion, terlipressin induces a significant and progressive decrease in variceal pressure but inconsistent variations of variceal pressure changes were seen after octreotide administration. This is probably related to its effect on central venous pressure. This study also shows that continuous variceal pressure recording with the non-invasive endoscopic registration technique detects in an accurate way the effect of vasoactive drugs on variceal pressure, because placebo injection did not produce significant changes.
Identification of the 85 kDa glycoprotein in the cholesterol crystallization promoting low density particle as carcinoembryonic antigen like cell adhesion molecule 1 (CEACAM1)
Authors: M. Jirsa, L. Muchova, L. Draberova, P. Draber, F. Smid, Z. Mareček, M. Küroki, A.K. Groen
Journal: Journal of Hepatology (2000)
Abstract 967: Establishing mechanisms of acquired resistance to Met inhibitor in Met-addicted gastric cancer cell lines.
Authors: Andrea Z. Lai, Crista Thompson, Sean Cory, Hong Zhao, Naila Chughtai, Michael Hallett, Morag Park
Journal: Cancer Research (2013)

Abstract Signaling by the Met, hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) activates multiple downstream signaling pathways that promote cell migration and invasive growth. Cells that overexpress and are “addicted” to Met also require Met signaling to sustain cell survival. Thus, a number of specific small-molecule inhibitors have been developed to target Met in the clinic. Although several successes of RTK-targeted therapies are acknowledged, most have had limited long-term success clinically due to development of drug resistance. As MET amplification occurs in 10-20% of gastric cancers, and MET-amplified cell lines are often exquisitely dependent on Met signaling for proliferation and survival, we established Met inhibitor-resistant clones derived from two different gastric cancer cell lines (MKN45 and KATO II) that are sensitive to Met inhibition. Treatment with a small-molecule inhibitor, PHA-665752 (PHA), specific to Met abrogates cell proliferation and anchorage-independent growth in these cells. In vitro selection of the most tumorigenic and resistant cells was performed by isolating colonies in anchorage-independent conditions with increasing PHA concentrations. Colonies were picked and expanded in 2D cell culture conditions and PHA concentration gradually increased until the cells were able to proliferate in a PHA concentration of &amp;gt;1μM (10x greater than the dose required for abrogation of proliferation in the parental cell lines). DNA, RNA, and protein have been isolated from each of the clones and sequencing, microarray analyses, phospho-RTK arrays, reverse-phase protein arrays (RPPA) have been utilized to identify the changes in signalling, protein and transcript expression that allow these cells to escape PHA inhibition. The analyses from these high-throughput assays will be presented here. As several Met inhibitors are presently in all three phases of clinical trials, and Met signalling has emerged as a means of escaping treatment by other targeted small-molecule kinase inhibitors, there exists a great need to determine the mechanisms through which cells may circumvent Met inhibition. The identification of resistance mechanisms will be essential for developing multi-pronged therapeutic strategies that may prove more efficacious at combatting tumorigenesis. Citation Format: Andrea Z. Lai, Crista Thompson, Sean Cory, Hong Zhao, Naila Chughtai, Michael Hallett, Morag Park. Establishing mechanisms of acquired resistance to Met inhibitor in Met-addicted gastric cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 967. doi:10.1158/1538-7445.AM2013-967
Failure of single dose amoxycillin as prophylaxis against endocarditis.
Authors: D W Denning, M Cassidy, A Dougall, W S Hillis
Journal: BMJ (1984)

the plastic syringcs was 6-7 days.Twenty seven patients used syringes for over seven days, one for up to 28 days.Of the 44 patients who used more than onie syringe a week, 17 bought their own extra syringes, three got them from district nurses, and 23 managed to defeat the system and get them from us.The mean duration of use of plastic syringes was shorter for patients receiving one injection a day (6-4 days) than for those receiving two injections a day (6-8 days).The group receiving once daily injections were mostly older patienits who had been taking insulin for many years (table ).Of the 118 patients, 18 had never tused glass syringes.Of the remaining 100, 83 preferred plastic syringes and 14 glass; three had no preference.Patients wvho preferred glass syringes had been injecting insulin for a longer mean timc (18 8 years) than the whole group (12-7 years).Of 31 paticnts who had beenI using glass syringes for over 20 years, however, 2_2 preferred plastic syringes.No complications occuLrred from reuse of plastic syringes.
Differential cytokine effects on primitive (CD34+CD38-) human hematopoietic cells: novel responses to Flt3-ligand and thrombopoietin.
Authors: A L Petzer, P W Zandstra, J M Piret, C J Eaves
Journal: The Journal of Experimental Medicine (1996)

A high proportion of the CD34+CD38- cells in normal human marrow are defined as long-term culture-initiating cells (LTC-IC) because they can proliferate and differentiate when co-cultured with cytokine-producing stromal feeder layers. In contrast, very few CD34+CD38- cells will divide in cytokine-containing methylcellulose and thus are not classifiable as direct colony-forming cells (CFC), although most can proliferate in serum-free liquid cultures containing certain soluble cytokines. Analysis of the effects of 16 cytokines on CD34+CD38- cells in the latter type of culture showed that Flt3-ligand (FL), Steel factor (SF), and interleukin (IL)-3 were both necessary and sufficient to obtain an approximately 30-fold amplification of the input LTC-IC population within 10 d. As single factors, only FL and thrombopoietin (TPO) stimulated a net increase in LTC-IC within 10 d. Interestingly, a significantly increased proportion of the CFC produced from the TPO-amplified LTC-IC were erythroid. Increases in the number of directly detectable CFC of &amp;gt; 500-fold were also obtainable within 10 d in serum-free cultures of CD34+CD38- cells. However, this required the presence of IL-6 and/or granulocyte/colony-stimulating factor and/or nerve growth factor beta in addition to FL, SF, and IL-3. Also, for this response, the most potent single-acting factor tested was IL-3, not FL. Identification of cytokine combinations that differentially stimulate primitive human hematopoietic cell self-renewal and lineage determination should facilitate analysis of the intracellular pathways that regulate these decisions as well as the development of improved ex vivo expansion and gene transfer protocols.
Analysis of anaphase in cell culture: an adequate test system for the distinction between compounds which selectively alter the chromosome structure or the mitotic apparatus.
Authors: R R Coutiño
Journal: Environmental Health Perspectives (1979)

A system of anaphase analysis is presented as an adequate test to detect aberrations in chromosome structure and alterations in the mitotic apparatus. Particular emphasis is placed on those data which suggest that proteins may be the preferred targets of chemical compounds that induce aneuploidy.
Cyclical Cushing's Syndrome
Authors: C. P. Aber, H. D. Cheetham
Journal: BMJ (1961)

MEDIBCrAL JoNAL studied 11 anaemic pregnant women in Gambia and treated eight with a high-protein diet for one to three months.He noted no improvement in haemoglobin concentration and also concluded that dietary deficiency of protein is not a cause of anaemia in pregnancy in Gambia.With the exception of the seroflocculation tests, no significant differences exist between the results of the liver-function tests in normal pregnancy and in pregnancy with anaemia.Of the anaemic patients, 10% had abnormal seroflocculation reactions, but this finding is considered to be secondary to the anaemia.It is clear from the analysis of our results that the majority of the anaemic patients must be free from severe liver disease.On the other hand, our data show dietary deficiencies of haemopoietic factors-and in particular deficiency of folic acid-to be important in producing the anaemias of pregnancy in Nigerian women.Summary The serum proteins and liver function of non-pregnant Nigerian women and of pregnant women, with and without anaemia, have been investigated.Dietary deficiency of protein and hepatic damage are not important aetiological factors in the anaemias of pregnancy in Nigerian women.The majority of the anaemic pregnant women had megaloblastic erythropoiesis.The response of the patients to treatment with antimalarials, iron, and folic acid was satisfactory.We are indebted to Drs.
ABC of ophthalmology. Visual difficulty in old age.
Authors: P A Gardiner
Journal: BMJ (1979)

Visual problems change with age YouthSo far as vision is concerned, there are three periods of life: up to the age 7-~^^îof 20 (development); from 20 to60 (maturity); and after 60 (the old eye).These ages are characterised by the changes in refraction that occur in Changes in some children and adolescents; changes in the power of accommodation refraction and the difficulties of the hypermetrope that occur in the latter half of middle age; and the absence of any refractive change in old age except those secondary to disease and degeneration.Before the age of 60 nearly all disorders of eyesight can be helped by Maturity glasses, though incipient disease may be responsible.After 60, however, most new disorders do not have a refractive origin, so that glasses are not *the main form of treatment and the dangers of self-diagnosis increase.Old people can fall into two gioups in their attitude towards their 4--r ?-., eyesight.Either they fail to understand when no glasses can help them, or .... :=._...
Role of Complement and Complement Regulatory Proteins in the Complications of Diabetes
Authors: Pamela Ghosh, Rupam Sahoo, Anand Vaidya, Michael Chorev, Jose A. Halperin
Journal: Endocrine Reviews (2015)

It is well established that the organ damage that complicates human diabetes is caused by prolonged hyperglycemia, but the cellular and molecular mechanisms by which high levels of glucose cause tissue damage in humans are still not fully understood. The prevalent hypothesis explaining the mechanisms that may underlie the pathogenesis of diabetes complications includes overproduction of reactive oxygen species, increased flux through the polyol pathway, overactivity of the hexosamine pathway causing intracellular formation of advanced glycation end products, and activation of protein kinase C isoforms. In addition, experimental and clinical evidence reported in past decades supports a strong link between the complement system, complement regulatory proteins, and the pathogenesis of diabetes complications. In this article, we summarize the body of evidence that supports a role for the complement system and complement regulatory proteins in the pathogenesis of diabetic vascular complications, with specific emphasis on the role of the membrane attack complex (MAC) and of CD59, an extracellular cell membrane-anchored inhibitor of MAC formation that is inactivated by nonenzymatic glycation. We discuss a pathogenic model of human diabetic complications in which a combination of CD59 inactivation by glycation and hyperglycemia-induced complement activation increases MAC deposition, activates pathways of intracellular signaling, and induces the release of proinflammatory, prothrombotic cytokines and growth factors. Combined, complement-dependent and complement-independent mechanisms induced by high glucose promote inflammation, proliferation, and thrombosis as characteristically seen in the target organs of diabetes complications.
Palliation may block cure of incontinence in elderly
Authors: Elaine Blume
Journal: JAMA (1983)

While urinary incontinence in the geriatric population is a major problem, the "prevailing pessimism regarding incontinence treatment is... not justified," says Mark E. Williams, MD, assistant professor of medicine at the University of Rochester School of Medicine and Dentistry. Williams elaborated on the subject recently at a Bethesda, Md, conference on "Evaluating the Elderly Patient: The Case for Assessment Technology." British surveys have disclosed that incontinence affects from 2% to 26% of elderly persons in the community (only about half of whom are known to health care providers) and from 13% to 48% of those in hospitals. Prevalence is not associated with sex, increasing age (within the older age population), or urinary infection, but it has been related to gynecologic and urologic surgery, drug use, physical disability, and neurologic disease. Incontinence results when bladder pressure is greater than sphincter resistance and, according to Williams, effective treatment depends on correctly classifying
Radical toxicity of phenols: A reference point for obtaining perspective in the formulation of QSAR
Authors: Rajni Garg, Sanjay Kapur, Corwin Hansch
Journal: Medicinal Research Reviews (2000)

In this report we discuss some of the surprising ways phenols interact in vivo and how some of their toxic activity can be understood in terms of QSAR and in fact can be related via electronic terms to be similar to processes of simple chemical reactions. A simple two-term QSAR is found to be a good predictor of estrogenic toxicity. However, it is also shown that even the simplest of phenols can yield quite unexpected results than can be elucidated via QSAR. We still have a long way to go before we can predict under what conditions a phenol will produce toxic effects such as cancer and how much phytophenols one can consume before reaping a toxic reaction. © 2000 John Wiley & Sons, Inc. Med Res Rev, 21, No. 1, 73–82, 2001
The Physiology of Emotions: Report of the Third Annual Symposium of the Kaiser Foundation Hospitals in North California, San Francisco
Authors: Stewart Wolf
Journal: JAMA (1961)

This comfortable-sized volume contains an absorbing and valuable summary of the data considered pertinent to the place of the emotions in the adaptive functions of man and animals. The authors, Brinker, Magoun, Hoagland, Ganong, Forsham, Kety, Goldfien, Elkes, Featherstone, Beach, Gerard, Pribram, Rioch, Herbert, Mead, Goldstein, and Weinstein, are a particularly articulate group of workers who see the ill-defined subject of emotions from many points of view. Each one proposes a thesis based on his interpretation of his own work and the related work of others. If there is a consensus, it is that patterns of reaction, either successfully adaptive or destructive, depend on the state of the organism and the state of the environment at the time, as well as on the significance of the stimulus-event to the affected individual. Neural, endocrine, and other chemical-mediating mechanisms are considered in a highly provocative way, with attempts to relate them to