tbuckley/cabot-search huggingface dataset:
Iron Deficiency Anemia: Have We Come Far Enough?
Authors: James A. Stockman
Journal: JAMA (1987)

In the progress of medical science, a disease is recognized, its manifestations are elucidated, and treatments or preventive measures are instituted; we then hope that the problem might become one of historical interest. Sometimes, however, we fail to realize when the problem still exists, and by our therapeutic misadventures create new problems. As demonstrated by the article of Yip et al<sup>1</sup>in this issue ofThe Journal, we indeed have come a long way in dealing with the problem of iron-deficiency anemia in childhood. When viewing the declining prevalence of anemia among low-income children in the United States, we should ask, however, if we have come far enough. To answer, it is useful to understand where we have been, where we are now, and in what directions we could be moving with respect to the prevention of iron deficiency. Iron is among the most common and useful of all
VISUAL EFFICIENCY IN INDUSTRY
Authors: ARTHUR M. CULLER
Journal: JAMA (1941)

In the first draft of the last war visual defects led all other causes for rejection and were three times as common as the next in importance. 1 Such common defects must receive the first attention of the industrial physician.  Psychologists have found that approximately six times as many perceptions are based on vision as on all the other senses combined. Industrial efficiency, therefore, depends almost directly on visual efficiency. The industrial physician is, in fact, caught between the horns of a dilemma when he considers the prime importance of visual efficiency and the great prevalence of visual defects. This means that he has the task not of weeding out the defectives but of evolving a program of visual efficiency which will increase industrial efficiency. This means that industry must not be disrupted by adherence to arbitrary visual standards but that the efficiency of the individual workman may be increased
Can the Genetics of Type 1 and Type 2 Diabetes Shed Light on the Genetics of Latent Autoimmune Diabetes in Adults?
Authors: Struan F. A. Grant, Hakon Hakonarson, Stanley Schwartz
Journal: Endocrine Reviews (2010)

The pathophysiology of latent autoimmune diabetes in adults (LADA) is considered less understood than its much better characterized counterparts of type 1 and type 2 diabetes (T1D and T2D), where its clinical presentation exhibits some features of each of these two main diseases, earning it a reputation as being "type 1.5 diabetes". The etiology of LADA remains unknown, but a genetic component has been implicated from recent reports of T1D and T2D genes playing a role in its pathogenesis. One way to shed much needed light on the classification of LADA is to determine the discrete genetic factors conferring risk to the pathogenesis of this specific phenotype and to determine to what extent LADA shares genetic similarities with T1D and T2D. For instance, no conclusive support for a role of the T1D-associated INS gene has been reported in T2D; conversely, but similarly, no evidence has been found for the role of the T2D-associated genes IDE/HHEX, SLC30A8, CDKAL1, CDKN2A/B, IGF2BP2, FTO, and TCF7L2 in T1D. However, and somewhat at odds with current thinking, TCF7L2, the most strongly associated gene with T2D to date, is strongly associated with LADA, a disorder considered by the World Health Organization to be a slowly progressing form of T1D. In this review, we address recent advances in the genetics of T1D and T2D and how such discoveries have in turn shed some light on the genetics of LADA as being potentially at the "genetic intersection" of these two major diseases.
Formation of reactive nitrogen species at biologic heme centers: a potential mechanism of nitric oxide-dependent toxicity.
Authors: Luigi Casella, Enrico Monzani, Raffaella Roncone, Stefania Nicolis, Alberto Sala, Antonio De Riso
Journal: Environmental Health Perspectives (2002)

The peroxidase-catalyzed nitration of tyrosine derivatives by nitrite and hydrogen peroxide has been studied in detail using the enzymes lactoperoxidase (LPO) from bovine milk and horseradish peroxidase (HRP). The results indicate the existence of two competing pathways, in which the nitrating species is either nitrogen dioxide or peroxynitrite. The first pathway involves one-electron oxidation of nitrite by the classical peroxidase intermediates compound I and compound II, whereas in the second pathway peroxynitrite is generated by reaction between enzyme-bound nitrite and hydrogen peroxide. The two mechanisms can be simultaneously operative, and their relative importance depends on the reagent concentrations. With HRP the peroxynitrite pathway contributes significantly only at relatively high nitrite concentrations, but for LPO this represents the main pathway even at relatively low (pathophysiological) nitrite concentrations and explains the high efficiency of the enzyme in the nitration. Myoglobin and hemoglobin are also active in the nitration of phenolic compounds, albeit with lower efficiency compared with peroxidases. In the case of myoglobin, endogenous nitration of the protein has been shown to occur in the absence of substrate. The main nitration site is the heme, but a small fraction of nitrated Tyr146 residue has been identified upon proteolytic digestion and high-performance liquid chromatography/mass spectrometry analysis of the peptide fragments. Preliminary investigation of the nitration of tryptophan derivatives by the peroxidase/nitrite/hydrogen peroxide systems shows that a complex pattern of isomeric nitration products is produced, and this pattern varies with nitrite concentration. Comparative experiments using chemical nitrating agents indicate that at low nitrite concentrations, the enzymatic nitration produces a regioisomeric mixture of nitrotryptophanyl derivatives resembling that obtained using nitrogen dioxide, whereas at high nitrite concentrations the product pattern resembles that obtained using peroxynitrite.
ChIP sequencing of cyclin D1 reveals a transcriptional role in chromosomal instability in mice
Authors: Mathew C. Casimiro, Marco Crosariol, Emanuele Loro, Adam Ertel, Zuoren Yu, William Dampier, Elizabeth A. Saria, Alex Papanikolaou, Timothy J. Stanek, Zhiping Li, Chenguang Wang, Paolo Fortina, Sankar Addya, Aydin Tozeren, Erik S. Knudsen, Andrew Arnold, Richard G. Pestell
Journal: Journal of Clinical Investigation (2012)

Chromosomal instability (CIN) in tumors is characterized by chromosomal abnormalities and an altered gene expression signature; however, the mechanism of CIN is poorly understood. CCND1 (which encodes cyclin D1) is overexpressed in human malignancies and has been shown to play a direct role in transcriptional regulation. Here, we used genome-wide ChIP sequencing and found that the DNA-bound form of cyclin D1 occupied the regulatory region of genes governing chromosomal integrity and mitochondrial biogenesis. Adding cyclin D1 back to Ccnd1–/– mouse embryonic fibroblasts resulted in CIN gene regulatory region occupancy by the DNA-bound form of cyclin D1 and induction of CIN gene expression. Furthermore, increased chromosomal aberrations, aneuploidy, and centrosome abnormalities were observed in the cyclin D1–rescued cells by spectral karyotyping and immunofluorescence. To assess cyclin D1 effects in vivo, we generated transgenic mice with acute and continuous mammary gland–targeted cyclin D1 expression. These transgenic mice presented with increased tumor prevalence and signature CIN gene profiles. Additionally, interrogation of gene expression from 2,254 human breast tumors revealed that cyclin D1 expression correlated with CIN in luminal B breast cancer. These data suggest that cyclin D1 contributes to CIN and tumorigenesis by directly regulating a transcriptional program that governs chromosomal stability.
Tandem versus single autologous peripheral blood stem cell transplantation as post-remission therapy in adult acute myeloid leukemia patients under 60 in first complete remission: results of the multicenter prospective phase III GOELAMS LAM-2001 trial
Authors: P Chevallier, L Fornecker, B Lioure, M C Béné, A Pigneux, C Recher, B Witz, N Fegueux, C-E Bulabois, S Daliphard, D Bouscary, N Vey, M Delain, J-O Bay, P Turlure, M Bernard, C Himberlin, I Luquet, N Ifrah, J-L Harousseau
Journal: Leukemia (2010)
SOME PHYSIOPATHOLOGICAL PARAMETERS OF NATURAL RESISTANCE TO INFECTION IN MURINE SALMONELLOSIS
Authors: Diethelm H. Böhme, Howard A. Schneider, Johanna M. Lee
Journal: The Journal of Experimental Medicine (1959)

Susceptible (BSVS) and resistant (BRVR) mice were experimentally infected with Salmonella typhimurium. The double strain inoculation technique was used in which both avirulent and virulent representatives of S. typhimurium were admitted into the hosts. The BSVS mice succumbed without exception while the BRVR mice survived to 52 per cent. No deaths occurred during the experimental period in non-infected control mice. Parallel to the survivorship test, and concurrent with it, the activity of the reticulo-endothelial system (RES) was measured at frequent intervals in identically infected BSVS and BRVR mice and in their non-infected controls. For this measurement the carbon clearance method was used. No pre-infection difference of activity of the RES could be discerned in susceptible BSVS mice vs. resistant BRVR. Following infection, increases in the RES activity were detected in about the same magnitude in both mouse stocks. However, a difference was found in the time of onset. The susceptible animals showed an early and short increase in the activity of the RES, followed by a drop to control levels at the time of death. The resistant group exhibited a considerably delayed, but significant increase in RES activity, which returned to control levels approximately 4 weeks after infection. The absolute white blood count did not undergo significant change in either of the two infected groups, but the susceptible animals showed a relative increase of their neutrophils at the expense of their lymphocytes. Extensive anatomical changes were observed in both mouse strains, mainly confined to liver and spleen. These consisted of stasis, swelling of Kupffer cells, necrotic foci, histiocytic-monocytic nodules, widespread thrombosis of branches of the portal and splenic veins, and extensive areas of necrosis. These changes appeared earlier in susceptible than in resistant animals. The implications of these findings are discussed.
Occupational asthma in a pharmaceutical worker exposed to penicillamine
Authors: F. Lagier, A. Cartier, J. Dolovich, J.-L. Malo
Journal: Thorax (1989)

A case of occupational asthma due to penicillamine is reported.Many drugs have been reported as causing occupational asthma.'2Penicillamine (C(CH3)2-SH-CHCOOH-NH2) is documented here as having caused occupational asthma in a pharmaceutical company worker. Case reportA 32 year old man had worked for 14 years as an operator in a
Ruptured Mesenteric Varix in Cirrhosis — Unusual Cause for Hemoperitoneum
Authors: John J. Rothschild, Irwin Gelernt, William Sloan
Journal: New England Journal of Medicine (1968)

THE occurrence of extensive collateral circulation is well known in association with portal hypertension. Existence of these hypertensive channels exposes patients to a continuous risk of serious hemorrhage. Esophageal and esophagogastric varices are the best known anatomic sites of hemorrhage. Other origins of bleeding have occasionally been cited. Recently, we observed a patient with rupture of a mesenteric varix resulting in hemoperitoneum and exsanguinating hemorrhage. To our knowledge this is a heretofore undescribed source of bleeding in cirrhosis.Case ReportA.G. (M.S.H. 317076), a 43-year-old man, was admitted to Mount Sinai Hospital on November 8, 1966, complaining of abdominal and . . .
Envelope-chimeric Entry-targeted Measles Virus Escapes Neutralization and Achieves Oncolysis
Authors: Tanner S Miest, Koon-Chu Yaiw, Marie Frenzke, Johanna Lampe, Andrew W Hudacek, Christoph Springfeld, Veronika von Messling, Guy Ungerechts, Roberto Cattaneo
Journal: Molecular Therapy (2011)

Measles virus (MV) is a promising vector for cancer therapy and multivalent vaccination, but high prevalence of pre-existing neutralizing antibodies may reduce therapeutic efficacy, particularly following systemic administration. MV has only one serotype, but here we show that its envelope glycoproteins can be exchanged with those of the closely related canine distemper virus (CDV), generating a chimeric virus capable of escaping neutralization. To target its entry, we displayed on the CDV attachment protein a single-chain antibody specific for a designated receptor. To enhance oncolytic efficacy we armed the virus with a prodrug convertase gene capable of locally activating chemotherapeutic prodrugs. The new virus achieved high titers, was genetically stable, and was resistant to neutralization by sera from both MV-immunized mice and MV-immune humans. The new virus targeted syngeneic murine tumor cells expressing the designated receptor implanted in immunocompetent mice, and synergized with a chemotherapeutic prodrug in a model of oncolysis. Importantly, the chimeric MV remained oncolytic when administered systemically even in the presence of anti-MV antibodies capable of abrogating the therapeutic efficacy of the parental, nonshielded MV. This work shows that targeting, arming, and shielding can be combined to generate a tumor-specific, neutralization-resistant virus that can synergize with chemotherapeutics. Measles virus (MV) is a promising vector for cancer therapy and multivalent vaccination, but high prevalence of pre-existing neutralizing antibodies may reduce therapeutic efficacy, particularly following systemic administration. MV has only one serotype, but here we show that its envelope glycoproteins can be exchanged with those of the closely related canine distemper virus (CDV), generating a chimeric virus capable of escaping neutralization. To target its entry, we displayed on the CDV attachment protein a single-chain antibody specific for a designated receptor. To enhance oncolytic efficacy we armed the virus with a prodrug convertase gene capable of locally activating chemotherapeutic prodrugs. The new virus achieved high titers, was genetically stable, and was resistant to neutralization by sera from both MV-immunized mice and MV-immune humans. The new virus targeted syngeneic murine tumor cells expressing the designated receptor implanted in immunocompetent mice, and synergized with a chemotherapeutic prodrug in a model of oncolysis. Importantly, the chimeric MV remained oncolytic when administered systemically even in the presence of anti-MV antibodies capable of abrogating the therapeutic efficacy of the parental, nonshielded MV. This work shows that targeting, arming, and shielding can be combined to generate a tumor-specific, neutralization-resistant virus that can synergize with chemotherapeutics.
The last laugh
Authors: Theodore Dalrymple
Journal: BMJ (2008)

I have always regarded critics of the medical profession as ill informed, ill intentioned, or ill adjusted—or, of course, all three. I have known several newspaper editors, for example, who were profoundly anti-doctor, a hostility I ascribe to the fact that doctors are held in far higher public esteem than journalists. If journalists cannot improve their own reputation, they can at least try to destroy that of others. Politicians are of the same ilk as journalists.

Of the great critics of the medical profession, none was more ferocious and uncompromising than Jean-Baptiste Poquelin, better known as Moliere. The last play he wrote was Le Malade Imaginaire , and as usual he makes fun of doctors …
Methadone Maintenance
Authors: Richard M. Glass
Journal: JAMA (1993)

In a 1965<i>JAMA</i>article, Dole and Nyswander<sup>1</sup>presented an initial evaluation of what was then a new treatment for heroin addiction: methadone maintenance. These pioneering physicians recognized that drug-free treatments for opiate addiction were rarely successful, and that except for overdoses, the severe medical complications of heroin addiction were due to the hazards of unsterile injections rather than direct drug toxic effects. They reported that prescription of daily doses of methadone hydrochloride, a long-acting and orally effective synthetic opioid, could relieve craving for heroin and block its euphoric effects while creating a condition of pharmacologic stability that permitted psychosocial treatment and rehabilitation of patients whose lives had previously been dominated by their addiction. See also p 1953. The development of this medical treatment abetted the conceptualization of addiction as a disease, and increased the involvement of physicians in its treatment. However, methadone maintenance treatment was immediately controversial<sup>2</sup>
INSPECTION OF THE JUGULAR VEIN; ITS VALUE AND ITS LIMITATIONS IN FUNCTIONAL DIAGNOSIS.A CRITICISM BY DR. HIRSCHFELDER AND A REPLY BY DR. McCASKEY. I. A CRITICISM.
Authors: ARTHUR D. HIRSCHFELDER
Journal: JAMA (1907)

The subject of heart-block and the recent additons to the knowledge of the allied functional disturbances of the heart and of the so-called cardiac neuroses have aroused a great deal of interest in the revelations from tracings of the venous pulse and polygraphic tracings. Although with appropriate apparatus<sup>1</sup>these are somewhat less difficult to obtain than are good radial pulse tracings, some form of rather expensive polygraph is necessary, and about half an hour is required to obtain the desired record.<sup>2</sup>Nevertheless so much information is to be gained by what they show that this procedure can scarcely be omitted from the modern routine examination of heart cases. It is, therefore, natural that efforts should be made to minimize the labor involved in such investigation, and in this regard the recent contribution of Dr. G. W. McCaskey<sup>3</sup>marks an attempt toward simplicity. By means of the Mackenzie
747 A 96-WEEK RANDOMIZED TRIAL OF SWITCHING TO ENTECAVIR IN CHRONIC HEPATITIS B PATIENTS WITH A COMPLETE VIROLOGIC RESPONSE TO LAMIVUDINE
Authors: J. Heo, S.H. Ahn, J.Y. Park, H.Y. Woo, H.J. Lee, W.Y. Tak, S.H. Um, K.T. Yoon, S.Y. Park, Y.S. Seo, C.W. Kim, K.H. Han, M. Cho
Journal: Journal of Hepatology (2013)
SRC is a signaling mediator in FLT3-ITD– but not in FLT3-TKD–positive AML
Authors: Hannes Leischner, Corinna Albers, Rebekka Grundler, Elena Razumovskaya, Karsten Spiekermann, Stefan Bohlander, Lars Rönnstrand, Katharina Götze, Christian Peschel, Justus Duyster
Journal: Blood (2012)
Gastric cancer detection in gastric ulcer disease.
Authors: R A Mountford, P Brown, P R Salmon, C Alvarenga, C S Neumann, A E Read
Journal: Gut (1980)

A retrospective study has been performed of all cases of gastric ulcer diagnosed or investigated within the Endoscopy Unit of the Department of Medicine, Bristol, over a three year period (1974-76). The average length of follow-up was two years. Two hundred and sixty five cases of gastric ulcer were studied of which 37 proved to be malignant (14%). Presenting complaints of anorexia, weight loss, nausea and/or vomiting, and multiple (greater than 3) symptoms, were commoner in the malignant ulcer group. Ulcer site and the presence of coexisting duodenal ulceration were largely unhelpful in deciding the status of an ulcer. Malignant ulcers tended to be large (greater than 1 cm diameter). Radiology was highly unreliable in distinguishing benign from malignant ulcers. Visual inspection at endoscopy was more reliable, but associated with a tendency to over-diagnose malignancy. False positive biopsies were uncommon (two cases). Three cases of clinically unsuspected superficial gastric carcinoma were revealed. Repeated endoscopy and biopsy of all gastric ulcers until they are completely healed is advised.
Myeloma cells inhibit non-canonical wnt co-receptor ror2 expression in human bone marrow osteoprogenitor cells: effect of wnt5a/ror2 pathway activation on the osteogenic differentiation impairment induced by myeloma cells
Authors: M Bolzoni, G Donofrio, P Storti, D Guasco, D Toscani, M Lazzaretti, S Bonomini, L Agnelli, A Capocefalo, B Dalla Palma, A Neri, F Nicolini, G Lisignoli, F Russo, S Colla, F Aversa, N Giuliani
Journal: Leukemia (2012)
Committee on Allied Health Education and Accreditation
Authors: Barbara Weithaus
Journal: JAMA (1991)

The American Medical Association (AMA), through its support of allied health education accreditation, plays an important role in maintaining professional standards, assuring that graduates of programs accredited by the AMA Committee on Allied Health Education and Accreditation (CAHEA) are qualified to perform their roles and functions and to work effectively with physicians. The specialized accreditation services provided by CAHEA contribute greatly to educational effectiveness and quality assurance. <h3>ACCREDITATION</h3> For more than 50 years the AMA and its members have recognized the value of actively participating in and promoting standards that maintain the quality of education for allied health personnel. This participation is increasingly important as it becomes more difficult to maintain an adequate supply of qualified professionals who complement, facilitate, or assist physicians as they provide health care services to the public. The AMA CAHEA is the most extensive specialized accrediting body in the nation. In accrediting educational programs that