tbuckley/cabot-search huggingface dataset:
Screening for familial hypercholesterolaemia
Authors: Ned Calonge, Janelle Guirguis-Blake
Journal: BMJ (2007)

Quinolinic acid (QUIN) is a potent endogenous excitotoxin, which has been shown to be present in the brain (Wolfensberger et al., 1983). In order to study the cellular localization of QUIN metabolism in the hippocampus, specific antibodies raised against purified rat liver 3- hydroxyanthranilic acid oxygenase (3HAO) and quinolinic acid phosphoribosyltransferase (QPRT), the enzymes directly responsible for QUIN synthesis and catabolism, respectively, were used for immunohistochemical studies in the adult male rat. Cells containing 3HAO immunoreactivity (3HAO-i) were present in all subfields of the hippocampal region, including the area dentata, Ammon9s horn, the subicular complex, and the entorhinal area. The highest density of 3HAO- i cells was found in the molecular layer of Ammon9s horn and in the hilus of area dentata, while the granular cell layer of area dentata and stratum pyramidale of Ammon9s horn contained the lowest number of 3HAO-stained cells. A majority of hippocampal 3HAO-i cells were also stained with monoclonal antibodies against glial fibrillary acidic protein (GFAP) or S-100 protein, suggesting that 3HAO-i is present primarily in astrocytes. At the ultrastructural level, 3HAO-i was found to be distributed uniformly throughout the cytoplasm, with intense immunostaining present in the internal and the external layers of the mitochondria. QPRT-i was detected in 3 morphologically distinct cell types present in all parts of the hippocampus. The total number of QPRT- i cells was lower than that of the 3HAO-i cells. QPRT-i cells were relatively numerous in the molecular and radial layers of Ammon9s horn, while they occurred only sporadically in stratum pyramidale of Ammon9s horn and in the granular cell layer of area dentata. Many QPRT-i cells stained with antibodies against GFAP and S-100, but the proportion of cells in which QPRT was colocalized with these glial marker proteins was lower than that for 3-HAO-i cells. At the ultrastructural level, 2 types of QPRT-i glial cells were detected. The smaller cell type had a diffuse cytoplasmic staining, while the larger cell type, which also contained glial filaments, showed diffuse cytoplasmic staining and intense staining of lysosomal structures. The observation that 3HAO and QPRT only partially coexist in hippocampal glial cells suggests that while synthesis and catabolism of QUIN may occur in the same glial cells, catabolism of QUIN can also take place in cells lacking the synthetic enzyme.
Roles of LAG3 and EGR2 in regulatory T cells
Authors: Tomohisa Okamura, Keishi Fujio, Shuji Sumitomo, Kazuhiko Yamamoto
Journal: Annals of the Rheumatic Diseases (2012)

Regulatory T cells (Tregs) participate in the maintenance of tolerance to self-antigens and suppressive control of excessive immune responses to exogenous antigens. A lack or dysfunction of these cells is responsible for the pathogenesis and development of many autoimmune diseases. It is well known that CD4 Tregs play a major role in controlling immune responses and can be classified into two main populations: thymus-derived naturally occurring Tregs (nTregs) and induced Tregs (iTregs) generated from CD4<sup>+</sup>CD25<sup>−</sup> precursors in the peripheral lymphoid organs. The most extensively studied Tregs are the nTregs, which express the interleukin 2 (IL-2) receptor CD25 and the transcription factor Forkhead box P3 (Foxp3). On the other hand, iTregs contain multiple heterogeneous subsets, including interleukin (IL)-10-producing CD4 type I Tregs (Tr1 cells) and transforming growth factor -β-producing Th3 cells, and so on. However, the extent of the contribution of iTregs to immunoregulation in normal animals has been difficult to evaluate because of the lack of suitable cell surface markers. It has been found recently that IL-10-secreting iTregs can be delineated as CD4<sup>+</sup>CD25<sup>−</sup>Foxp3<sup>−</sup> T cells that characteristically express both the lymphocyte activation gene-3 (<i>LAG3</i>) and the early growth response gene-2 (<i>EGR2</i>). In this review, opinions about the roles of <i>LAG3</i> and <i>EGR2</i> in Tregs are presented.
Initial Treatment for HIV Infection — An Embarrassment of Riches
Authors: Bernard Hirschel, Alexandra Calmy
Journal: New England Journal of Medicine (2008)

Drugs that are used to treat patients with human immunodeficiency virus (HIV) infection are classified according to their target. The first ones to be developed were nucleoside reverse-transcriptase inhibitors (NRTIs), which lead to premature termination of the nascent DNA chain, and nonnucleoside reverse-transcriptase inhibitors (NNRTIs), which bind and inhibit reverse transcriptase. The viral protease inhibitors were next. NRTIs, NNRTIs, and protease inhibitors remain the staples of highly active antiretroviral therapy, but other targets, such as the CCR5 receptor, the fusion peptide, and viral integrase, have recently yielded promising molecules.At this time, eradication of HIV is impossible. Rebound inevitably follows . . .
Life Changes Related to the Onset of Juvenile Rheumatoid Arthritis
Authors: Liisa Keltikangas-Järvinen, Pirkko Pelkonen, Ilkka Kunnamo
Journal: Psychotherapy and Psychosomatics (1988)

Life changes preceding the onset of juvenile rheumatoid arthritis (JRA) were studied in 49 children with prolonged arthritis, and in 58 children with temporary arthritis. In addition, the frequency of changes experienced by patients during their life was compared with the expectancy scores for healthy children. The frequency of changes during the year prior to the onset of the disease did not differentiate children with JRA from children with temporary arthritis. During their lives, the children of both groups had experienced a higher frequency of life changes requiring considerable readjustment than healthy children of the same age.
A Computer-Based Medical Record
Authors: Joseph M. Kiely
Journal: JAMA (1968)

The Mayo Clinic has had preliminary experience with a computer-input system which employs video screen and light-pen and allows the physician to use ordinary English language for entry and retrieval of historical and physical-examination data. The system allows the clinician convenient, rapid, direct interaction with a computer-based, medical-information system. Use of this technique results in clinical records that are carefully formatted, complete and legible, and easily retrievable either on the video screen or as printed copy. These improved attributes of the clinical record should result in better patient care and facilitate retrieval of data for clinical research.
ENTEROTOXIGENIC ESCHERICHIA COLI AND REOVIRUS-LIKE AGENT IN RURAL BANGLADESH
Authors: RobertW Ryder, DavidA Sack, AlbertZ Kapikian, JamesC Mclaughlin, Jyotsnamoy Chakraborty, A.S.M Mizanur Rahman, MichaelH Merson, JoyG Wells
Journal: The Lancet (1976)
Effect of Azelastine Hydrochloride on Macrophage Chemotaxis and Phagocytosis <i>in Vitro</i>
Authors: Mitsuo Honda, Kazunori Miura, Tomio Tanigawa
Journal: Allergy (1982)

Azelastine, a newly synthesized anti-allergic agent, was tested for its effects on guinea pig macrophage chemotaxis and phagocytosis. As specific macrophage chemo-attractants, we used macrophage chemotactic factors a and c; separated and highly purified from inflamed skin sites. Macrophage chemotaxis induced by skin extract or chemotactic factors was significantly suppressed by a low concentration of the agent (1 microgram/ml); the effect was dose-dependent. The inhibition of chemotaxis was reversible, because chemotactic activity was restored when the agents was removed by washing cells before chemotactic assay. Inactivation of chemotactic factors was not detected by mixing azelastine and factors a and c. Azelastine may directly interact with macrophages to decrease their chemotactic responsiveness. beta-Glucuronidase activity in the medium and macrophages after phagocytosis of polystyrene latex particles was not affected by this agent at concentrations ranging from 1 to 10 micrograms/ml. The phagocytosis of latex particles or sheep red blood cells opsonized with IgG antibodies (EA) and anchoring of macrophages to substrate were not inhibited and azelastine did not damage the macrophages as determined by lactate dehydrogenase (LDH) release assay.
The MRCGP examination and accident and emergency departments
Authors: W H Konarzewski
Journal: BMJ (1983)

SIR,-We have recently completed a survey of chronic leg ulcers in the Lothian and Forth Valley areas.We have identified 1690 patients with this condition, of whom 68 O were being managed entirely in the community by district nurses and general practitioners.We shall be reporting this study shortly.Our purpose in writing at this early stage is to express our concern that the survey has engendered with regard to serious inadequacies in the Drug
Stratified random allocation
Authors: P. Sedgwick
Journal: BMJ (2013)

Researchers investigated the effects of manual lymph drainage on the development of lymphoedema related to breast cancer. A randomised single blinded controlled trial was performed. The intervention was a six months’ treatment programme consisting of guidelines about prevention of lymphoedema, exercise therapy, and manual lymph drainage. Control treatment consisted of the same programme as the intervention but without manual lymph drainage.1

Participants were consecutive patients with breast cancer and unilateral axillary lymph node dissection. Randomisation to treatment groups occurred in a 1:1 ratio using stratification by body mass index (≤25 or >25) and postoperative axillary irradiation (yes or no). Allocation was achieved using random permuted blocks of size four. In total, 160 patients were recruited, with 79 allocated to the intervention and 81 allocated to control.

The main outcome measures were incidence of arm lymphoedema and time until development of arm lymphoedema. One year after surgery, there was no significant difference between treatment groups in the cumulative incidence rate for arm lymphoedema and the time to development of arm lymphoedema.

Which of the following …
Offshore schools loan regs revamped
Authors: A. A. Skolnick
Journal: JAMA (1995)

AFTER YEARS of neglecting its congressionally mandated responsibility, the US Department of Education is putting the final touches on new regulations for determining which foreign medical schools are eligible to participate in the Federal Family Educational Loan (FFEL) program.  However, these final touches may touch off angry protests as well as lawsuits if they accomplish what Congress has mandated in the Higher Education Act Amendment of 1992—to deny federally insured loans to students attending foreign medical schools that fail to meet the same standards US and Canadian schools must meet.  Many of these  schools, which primarily enroll US citizens, depend heavily on tuition paid with FFEL program loans. These loans are the only federal educational assistance funds available to Americans studying abroad. At least some of these for-profit, offshore schools may not stay open if eligibility for the loan program is denied.  To satisfy the new regulations, substandard schools
Influence of superimposed alcoholic hepatitis on the outcome of liver transplantation for end-stage alcoholic liver disease
Authors: Santiago Tomé, Carmen Martinez-Rey, Arturo González-Quintela, Francisco Gude, Antonio Brage, Esteban Otero, Ihab Abdulkader, Jerónimo Forteza, Manuel Bustamante, Evaristo Varo
Journal: Journal of Hepatology (2002)
FREE NORADRENALINE AND ADRENALINE EXCRETION IN RELATION TO THE DEVELOPMENT OF CARDIAC ARRHYTHMIAS AND HEART-FAILURE IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION
Authors: D.E. Jewitt, D. Reid, M. Thomas, C.J. Mercer, C. Valori, J.P. Shillingford
Journal: The Lancet (1969)
Role of Simvastatin as an Immunomodulator in Type 2 Diabetes
Authors: Michelle Petrou, Marialena Gregoriades, Vassilios Vassiliou
Journal: Diabetes Care (2004)

In reading the article by Lopes-Virella et al. (1), we were rather concerned that the authors referred to “creatinine kinase” as a marker of cardiac injury. We are certain that the authors wanted to refer to …
Early diagnosis of infantile seborrhoeic dermatitis and atopic dermatitis—total and specific IgE levels
Authors: VICTORIA M. YATES, REBECCA E.I. KERR, K. FRIER, S.J. COBB, RONA M. MacKIE
Journal: British Journal of Dermatology (1983)

Journal Article Early diagnosis of infantile seborrhoeic dermatitis and atopic dermatitis—total and specific IgE levels Get access VICTORIA M. YATES, VICTORIA M. YATES Department of Dermatology, Stobhill General Hospital, Glasgow Dr V.M. Yates, The Skin Hospital, Quay St., Manchester M3 3HL. Search for other works by this author on: Oxford Academic Google Scholar REBECCA E.I. KERR, REBECCA E.I. KERR Department of Dermatology, Stobhill General Hospital, Glasgow Search for other works by this author on: Oxford Academic Google Scholar K. FRIER, K. FRIER Department of Immunology Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar S.J. COBB, S.J. COBB Department of Immunology Western Infirmary, Glasgow Search for other works by this author on: Oxford Academic Google Scholar RONA M. MacKIE RONA M. MacKIE University Department of Dermatology, Glasgow Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 108, Issue 6, 1 June 1983, Pages 639–645, https://doi.org/10.1111/j.1365-2133.1983.tb01075.x Published: 01 June 1983 Article history Accepted: 12 October 1982 Published: 01 June 1983
The Anticoagulant Activity of Lysosomal Cationic Proteins from Polymorphonuclear Leukocytes *
Authors: Hussain I. Saba, Harold R. Roberts, John C. Herion
Journal: Journal of Clinical Investigation (1967)

A cationic protein fraction from rabbit polymorphonuclear leukocyte lysosomes has been shown to exert a potent anticoagulant effect on human blood in vitro. The anticoagulant activity is detectable in the whole blood clotting time, the recalcification time of platelet-rich plasma, the prothrombin time, the partial thromboplastin time, and the thromboplastin generation test. The lysosomal cationic proteins do not inhibit any of the known specific procoagulants. They appear to inhibit clotting by blocking the formation of intrinsic thromboplastin possibly by interfering with the role of phospholipids in the reaction involving Factors V and X and calcium.
RABBIT ANTIBODIES TO STREPTOCOCCAL CARBOHYDRATES
Authors: Dietmar G. Braun, Klaus Eichmann, Richard M. Krause
Journal: The Journal of Experimental Medicine (1969)

In a search for possible genetic factors which may influence the immune response to the streptococcal carbohydrates, over 100 rabbits have been immunized with streptococcal vaccines, and representative examples of high and low response pairs mated. The concentration of precipitins to the group—specific carbohydrates has been measured in the antisera following primary intravenous immunization with heat-killed streptococcal vaccines, Group A, Group A-variant, and Group C. For the majority of rabbits, the concentration of precipitins varied between 1 and 10 mg/ml of antiserum; while in the minority, it was between 11 and 32 mg/ml. The offspring of rabbits with high antibody levels had a significantly higher concentration of antibody than was seen in the offspring of rabbits of low response parents. Such data suggest that the magnitude of the immune response to these carbohydrate antigens is under some form of genetic control. Not uncommonly in rabbits with hyper-γ-globulinemia following primary immunization, the group-specific precipitins are the predominant component of the γ-globulin. An unusual feature of such components is that they are electrophoretically monodisperse, and possess individual antigenic specificity. In this respect they resemble the myeloma proteins. When a response of this sort is not seen after primary immunization, it may occur after secondary immunization. Therefore, prior exposure to the same or closely related antigen may also have an influence on the occurrence of high concentrations of such uniform antibodies.
Pseudotumor Cerebri Associated With Prolonged Corticosteroid Therapy
Authors: A. Earl Walker, J. J. Adamkiewicz
Journal: JAMA (1964)

An endocrine factor appears to be one of the causes of benign intracranial hypertension. The occurrence of the pseudotumoral syndrome has been seen in children receiving corticosteroids over prolonged periods of time for various conditions. The clinical manifestations of headache, nausea, vomiting, and papilledema tend to occur during the reduction or withdrawal phase of therapy. The blood electrolyte levels are normal but urinary steroid excretion may be low. Although the cerebrospinal fluid pressure is elevated, the ventricles may be small. A transient hypophyseal adrenal suppression appears to be an underlying mechanism. The condition is usually self-limited with appropriate management. The authors review the clinical features of the reported cases and of four patients seen at the Johns Hopkins Hospital.
Maternal tobacco smoke exposure and persistent pulmonary hypertension of the newborn.
Authors: C Bearer, R K Emerson, M A O'Riordan, E Roitman, C Shackleton
Journal: Environmental Health Perspectives (1997)

We propose that in utero exposure to tobacco smoke products places a newborn at risk for persistent pulmonary hypertension of the newborn (PPHN). To test this hypothesis, infants with PPHN were identified. Healthy newborns of similar ethnicity were identified as a comparison group. Cord blood cotinine concentrations and maternal questionnaires were obtained. The number of women exposed to tobacco smoke in each group ascertained by questionnaire was borderline significantly different (38.7% vs. 20.5%; p = 0.080). However, more PPHN infants had detectable cotinine in their cord blood (64.5% vs. 28.2%; p = 0.002), and the median cotinine concentrations were significantly higher (5.2 ng/ml vs. 2 ng/ml; p = 0.051) than the comparison infants. Among infants delivered to nonsmoking women, more PPHN infants had detectable cotinine (50% vs. 19%; p = 0.015), and the cotinine concentrations were higher (3.5 ng/ml vs. 1.65 ng/ml; p = 0.022) than the comparison group. We conclude that active and passive smoking during pregnancy is a risk factor for PPHN. Therefore, we recommend that pregnant women cease smoking and avoid environmental tobacco smoke. Key words. cotinine, newborns, passive, persistent pulmonary hypertension, smoking, tobacco smoke pollution.
Cost Savings at the End of Life
Authors: Ezekiel J. Emanuel
Journal: JAMA (1996)

Medical care at the end of life consumes 10% to 12% of the total health care budget and 27% of the Medicare budget. Many people claim that increased use of hospice and advance directives and lower use of high-technology interventions for terminally ill patients will produce significant cost savings. However, the studies on cost savings from hospice and advance directives are not definitive. The 3 randomized trials show no savings from these interventions, but either they are too small for confidence in their negative results or their intervention and cost accounting are flawed. The nonrandomized trials of hospice and advance directives show a wide range of savings, from 68% to none. Five methodological issues obscure the assessment of these studies: (1) selection bias in those patients who use hospice and advance directives, (2) the different time frames of assessing the costs, (3) the limited types of medical costs evaluated, (4) the variability of reporting the savings, and (5) the lack of generalizability of the findings to other patient populations. A more definitive study that assessed patients' end-of-life care preferences, use of hospice and advance directives, and direct and indirect costs would be desirable. In the absence of such a study, the existing data suggest that hospice and advance directives can save between 25% and 40% of health care costs during the last month of life, with savings decreasing to 10% to 17% over the last 6 months of life and decreasing further to 0% to 10% over the last 12 months of life. These savings are less than most people anticipate. Nevertheless, they do indicate that hospice and advance directives should be encouraged because they certainly do not cost more and they provide a means for patients to exercise their autonomy over end-of-life decisions. (<i>JAMA</i>. 1996;275:1907-1914)
Abstract A18: CDK6 binds and promotes the degradation of the EYA2 protein
Authors: Dawn Kohrt, Jennifer Crary, Marc Zimmer, Heide Ford, Phi Hinds, Martha Grossel
Journal: Cancer Research (2013)

Abstract Cyclin dependent kinase 6 (Cdk6) is a D-cyclin activated kinase that is directly involved in driving the cell cycle through inactivation of pRB in G1 phase. Increasingly, evidence suggests that CDK6, while directly driving the cell cycle, may only be essential for proliferation of specialized cell types, agreeing with the notion that CDK6 also plays an important role in differentiation. Here, evidence is presented that CDK6 binds to and promotes degradation of the EYA2 protein. The EYA proteins are a family of proteins that activate genes essential for the development of multiple organs, regulate cell proliferation, and are misregulated in several types of cancer. This interaction suggests that CDK6 regulates EYA2 activity, a mechanism that could be important in development and in cancer. Citation Format: Dawn Kohrt, Jennifer Crary, Marc Zimmer, Heide Ford, Phi Hinds, Martha Grossel. CDK6 binds and promotes the degradation of the EYA2 protein. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A18.
Demography in Early America: Beginnings of the Statistical Mind, 1600-1800
Authors: Gert H. Brieger
Journal: JAMA (1970)

We now take for granted that the statistical treatment of social and scientific affairs can yield important insights. In this book, Dr. Cassedy, from the History of Medicine Division of the National Library of Medicine, describes the introduction of vital statistics in the United States before 1800. In quick progression he discusses the role of numbers in the religious and secular affairs of the early colonists, the census, bills of mortality, life expectancy figures, and the statistical approach to disease. The growth of colonial America, Cassedy concludes, coincided with the emergence of new statistical concepts in Europe. Without much lag-time these early statistical activities also found application in the thinking of Americans. Even so, by the end of the book, one must still conclude, as Cassedy does, that "two centuries of statistical activities had not really brought Americans very far beyond a simple quantitative way of looking at things." The