tbuckley/cabot-search huggingface dataset:
Possible Etiologic Mechanisms in Chemical Carcinogenesis
Authors: Emmanuel Farber
Journal: Environmental Health Perspectives (1987)

Some highlights in the development of our knowledge about carcinogens as etiological agents for cancer are reviewed briefly.Advances during the past 20 years relating to metabolic activation with the genesis of reactive metabolites, molecular targets and their interactions with activated carcinogens, oncogenes as molecular targets and the dependence on cell proliferation, all relating to the initiation process, are reviewed.Critical to initiation is the new phenotype in the initiated cell, known only in one instance, the rat liver, in which the characteristic change is one of resistance to many xenobiotic influences.The need for clonal expansion of initiated cells as essential for carcinogenic effects is discussed.Differential in- hibition has been shown as a dominant mechanistic pattern in the liver.In other systems, the manner in which clonal expansion is achieved is not evident.The need for studies of the processes involved in carcinogenesis, as well as the agents, is emphasized, in view of the continuing validity of the cell concept as the key to integrating the increasingly large volume of data from the molecular with the biological.
Effects of sulfite on the uptake and binding of benzo[a]pyrene diol epoxide in cultured murine respiratory epithelial cells.
Authors: J L Green, B C Jones, G A Reed
Journal: Environmental Health Perspectives (1994)

Sulfur dioxide (SO2) may act as a cocarcinogen with benzo[a]pyrene (BaP) in the respiratory tract. We have modeled this effect by examining the interactions of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with sulfite, the physiological form of SO2, in a murine respiratory epithelial cell line (C10). We exposed C10 cells to [3H]-anti-BPDE and determined the effects of 1 and 10 mM sulfite on the uptake and subcellular localization of labeled products. Autoradiographic analysis showed that sulfite doubled the nuclear localization of anti-BPDE-derived materials after a 4-hr incubation period. The net nuclear localization of anti-BPDE-derived materials was not affected by sulfite during the first 60 min, but nuclear localization continued to increase in the sulfite-containing incubations throughout the 4-hr incubation period. Little increase in nuclear localization of anti-BPDE-derived material was noted in the incubations without sulfite after 60 min. Subcellular fractionation was performed to determine the amount of label associated with cytosolic and nuclear fractions and to determine covalent binding to protein and DNA. Sulfite produced a modest increase in the amount of [3H]-anti-BPDE-derived products bound to protein; however, binding to nuclear DNA increased by more than 200% with 10 mM sulfite. Analysis of the supernatants from the cytosolic and nuclear fractions of cells exposed to anti-BPDE and sulfite demonstrated the presence of 7r,8t,9t-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10c-su lfonate (BPT-10-sulfonate). [3H]-BPT-10-sulfonate was unable to enter C10 cells, suggesting that it is formed intracellularly.(ABSTRACT TRUNCATED AT 250 WORDS)
Infarct size limitation by the xanthine oxidase inhibitor, allopurinol, in closed-chest dogs with small infarcts
Authors: S. AKIZUKI, S. YOSHIDA, D. E CHAMBERS, L. J EDDY, L. F PARMLEY, D. M YELLON, J. M DOWNEY
Journal: Cardiovascular Research (1985)

The present study was designed to evaluate the ability of allopurinol to limit infarct size following permanent coronary occlusion in the greyhound. Coronary occlusion was produced by injecting 2.5 mm plastic beads into the coronary artery of the closed chest dog. Non-perfused myocardium, the area at risk, was visualised by autoradiography of l41Cerium labelled microspheres which were infused immediately following coronary embolization. The treated dogs (n = 12) received 400 mg of allopurinol orally one day before surgery. A 25 mg·kg−1bolus was administered (iv) immediately before occlusion, and repeated every 8 h. 11 dogs served as controls. After 24 h, the dogs were killed and the hearts were sliced into 5.0 mm transverse sections. The infarcted myocardium was visualised by triphenyl tetrazolium chloride staining. The percentage of the risk zone which evolved to infarct was calculated. This percentage was 18.1 ± 3.95% in the allopurinol group vs 58.4 ± 2.81% in the control group (p<0.001). We conclude that allopurinol is a potent drug for the limitation of infarct size in the dog with permanent coronary occlusion.
Carcinoma of the Urinary Bladder
Authors: William L. Caldwell
Journal: JAMA (1974)

CARCINOMA of the urinary bladder is primarily a disease of the elderly, with a peak incidence among those 60 to 70 years old. Each year approximately 9,000 persons in the United States die of urinary bladder cancer, the incidence being three times as frequent in men as in women. The cause of the vast majority of urinary bladder tumors has not been determined. Nevertheless, several causative agents (such as 2-naphthalamine, xenylamine, 4-nitrobiphenyl, benzidine, phenacetin, and caffeine) have been identified as carcinogens, and an increased incidence of bladder carcinoma is reported in workers in the rubber, printing, and leather industries.<sup>1</sup> Most bladder carcinomas are transitional cell tumors of varying degrees of differentiation. Squamous cell metaplasia is seen in many transitional cell carcinomas, particularly the less well-differentiated ones. However, except when schistosomiasis is the cause, true squamous cell carcinomas are rare. Adenocarcinomas also are uncommon. On initial examination, the commonest sign
Thioridazine in Schizophrenia
Authors: Bruce E. Carlson
Journal: JAMA (1971)

<h3>To the Editor.—</h3> At Norristown (Pa) State Hospital, we have had considerable experience in the use of thioridazine (Mellaril), primarily with schizophrenics, but also with patients with nonpsychotic severe anxiety reactions. It is well known that thioridazine, because of its adrenolytic activity, inhibits or prevents ejaculation in some patients. Though not specifically dose-related, this phenomenon is generally more severe at higher dosages. Thioridazine has been shown to cause impotency in males and delay of orgasm in both men and women. Occasionally, thioridazine has been found to be effective in the treatment of premature ejaculation, prolonging the time between insertion and ejaculation. The exact basis of this effect is unknown but may be related to decrease in anxiety or a specific chemical effect on the sexual functioning. Schizophrenics, generally, are most disturbed by any changes in bodily function, whatever the cause, but especially in their sexual functioning. With the use of
Predicting health effects of exposures to compounds with estrogenic activity: methodological issues.
Authors: R Rudel
Journal: Environmental Health Perspectives (1997)

Many substances are active in in vitro tests for estrogenic activity, but data from multigenerational and other toxicity studies are not available for many of those substances. Controversy has arisen, therefore, concerning the likelihood of adverse health effects. Based on a toxic equivalence factor risk assessment approach, some researchers have concluded that exposure to environmental estrogens is not associated with estrogen receptor (ER)-mediated health effects. Their rationale cites the low potency of these compounds in in vitro assays relative to estradiol, and the widespread exposure to pharmaceutical, endogenous, and dietary estrogens. This reasoning relies on two assumptions: that the relative estrogenic potency in in vitro assays is predictive of the relative potency for the most sensitive in vivo estrogenic effect; and that all estrogens act via the same mechanism to produce the most sensitive in vivo estrogenic effect. Experimental data reviewed here suggest that these assumptions may be inappropriate because diversity in both mechanism and effect exists for estrogenic compounds. Examples include variations in ER-ligand binding to estrogen response elements, time course of nuclear ER accumulation, patterns of gene activation, and other mechanistic characteristics that are not reflected in many in vitro assays, but may have significance for ER-mediated in vivo effects. In light of these data, this report identifies emerging methodological issues in risk assessment for estrogenic compounds: the need to address differences in in vivo end points of concern and the associated mechanisms; pharmacokinetics; the crucial role of timing and duration of exposure; interactions; and non-ER-mediated activities of estrogenic compounds.
Chediak-Higashi gene in humans. II. The selectivity of the defect in natural- killer and antibody-dependent cell-mediated cytotoxicity function
Authors: M Klein, J Roder, T Haliotis, S Korec, Jett JR, RB Herberman, P Katz, AS Fauci
Journal: The Journal of Experimental Medicine (1980)

Antibody-dependent cell-mediated cytolysis (ADCC) of human tumor cells by FcR(+) nonadherent effector lymphocytes as well as natural killer (NK) activity was markedly impaired in Chediak-Steinbrinck-Higashi Syndrome (C-HS) patients. Compared to a more than 400-fold defect in NK activity in terms of lytic units, the abnormal ADCC response in C-HS donors was 24-fold below normal suggesting a partial but not complete overlap of lymphocytes or lytic mechanisms responsible for ADCC and NK. The ADCC mechanism against erythrocyte targets, however, was normal, thereby suggesting a qualitative difference in these two forms of ADCC. Other effector-cell functions against tumor-cell targets were normal as measured by (a) spontaneous cytolysis mediated by monocytes, (b) spontaneous cytostasis mediated by neutrophils, and (c) lectin-dependent cytolysis mediated by neutrophils. Although one C-HS patient was low in lectin-dependent cytolysis mediated by lymphocytes, the other C-HS patient was normal, thereby suggesting that cytolytic T function was not linked to the NK-ADCC defect. In addition, the proliferative response to T-dependent mitogens was also relatively normal. These results, combined with other studies showing normal cell-mediated and humoral immunity in these same patients, suggest that patients with C-HS have an immunodeficiency which is selective for NK and ADCC activity.
Cost-effectiveness of distal embolic protection for patients undergoing percutaneous intervention of saphenous vein bypass grafts
Authors: David J. Cohen, Sabina A. Murphy, Donald S. Baim, Tara A. Lavelle, Ronna H. Berezin, Donald E. Cutlip, Kalon K.L. Ho, Richard E. Kuntz
Journal: Journal of the American College of Cardiology (2004)
Suspected cases of pulmonary tuberculosis referred from port of entry into Great Britain, 1980-3.
Authors: A C Markey, S M Forster, R Mitchell, E Larson, H Smith, C J Dore
Journal: BMJ (1986)

Revue de 203 dossiers, concernant principalement de jeunes immigrants provenant de l'Inde. Les aspects radiologiques et cliniques suggerent la tuberculose dans la plupart des cas. Les cultures sont positives pour M. tuberculosis dans 44 cas, negatives dans 140 cas. 80% des malades sont consideres comme a haut risque et doivent etre etroitement surveilles
Case of Retroversion of the Uterus at the Sixth Month of Pregnancy
Authors: J. Seddon
Journal: BMJ (1848)

In the case of a female, aged 43, affected with catalepsy, whom I am now attending, I found the use of chloroform of infinite service, enabling me to administer medicine which was otherwise imupracticable.This is the second time I have been consulted within the last tbree months.The first time I saw her was subsequent to the cataleptic state, but now it came on during my attendance, so that I had every opportunity of watching its progression and decline.When the cataleptic state was perfect, and had lasted for sixteen hours, after trying turpentine stimuli externally, and enemata, which proved of no avail, I presented the vapour of chloroform to her nostrils and mouth by means of a hbandkerchief.The fourth inspiration produced a change.Each inhalation, previously inaudible, now became prolonged and loud, as though the vapour gave great satisfaction.The pulse, which had been 56 was increased to 84 ; the iris gained its wonted power and sensation, and the limbs, with every volun- tary muscle in the body, were now again obedient to the will.This being just what I wanted, I made her sit up and take some medicine, which could not be done before, on account of the existence of trismus.She soon again sank into her former state, but from that hour her recovery commenced.
The influence of delayed compressive stress on TGF-β1-induced chondrogenic differentiation of rat BMSCs through Smad-dependent and Smad-independent pathways
Authors: Juan Li, Jun Wang, Yuanwen Zou, Yifan Zhang, Dan Long, Lei Lei, Lijun Tan, Rui Ye, Xuejin Wang, Zhihe Zhao
Journal: Biomaterials (2012)
Recognition of Hapten-Modified Cells In Vitro by Human T Lymphocytes
Authors: Michael F. Seldin, Robert R. Rich, Stuart L. Abramson
Journal: Journal of Clinical Investigation (1979)

Clearer definition of the recognitive structures of human T lymphocytes for antigens will be required to elucidate the molecular basis of diseases and immunological responses induced or regulated by normal or abnormal T-cell function. For this purpose we have investigated the cellular requirements for immune responses in vitro to trinitrophenyl-conjugated peripheral blood mononuclear cells. The responding cell was characterized as a T cell on the basis of rosetting with sheep erythrocytes. T-cell recognition of hapten in proliferative responses depended upon presentation of antigen in an appropriate stimulator-cell context. Neither autologous hapten-modified erythrocytes nor T cells restimulated responses of in vitro-primed lymphocytes. Moreover, hapten-conjugated non-T cells were more effective than modified unfractionated cells in restimulating proliferative responses. Both macrophages and non-T lymphocytes effectively restimulated hapten-conjugate responses.
An ultrasonic displacement instrument with greater beam dispersal
Authors: G. A. MCGOUGH, D. BREAZEALE, G. L. MULLINS, W. G. GUNTHEROTH
Journal: Cardiovascular Research (1973)

An ultrasonic transit time device was modified to permit close placement of the crystals and to broaden the effective spatial angle of the beam of ultrasound. The device is ideal for chronic animal experiments since its output is linear for displacement and calibration may be performed at any time.
The Excitement and Fascination of Science: Reflection by Eminent Scientists
Authors: Richard E. Peschel
Journal: JAMA (1991)

Nuclear physicist Emilio Segrè offers the best reason that physicians and health professionals should read this collection of autobiographical reflections by over 110 scientists from 18 different scientific disciplines: "My father once told me, 'You are living on Fermi's crumbs' " (p 1361). Health care professionals today can provide excellent medical care to patients only by standing on the shoulders of the scientific giants (or living on the crumbs of these great men and women, to use the words of Segrè's father) who have contributed so much to the basic scientific underpinnings of medicine and the fabric of our technological society. This two-volume collection has 18 sections organized by scientific discipline with 112 autobiographical chapters written by leaders in their fields. The 2338 pages present a mosaic of the scientific foundations of modern Western civilization. A sample of the vignettes, history, scientific information, and insights into the scientific method recounted in
LIMITED LINEAR ABLATION FOR REGIONAL SCAR ENCIRCLING TO TREAT POST-INFARCTION VENTRICULAR TACHYCARDIA USING A STANDARDIZED MAPPING AND ABLATION APPROACH
Authors: Thomas Deneke, Thomas Lawo, Dong-In Shin, Marc Horlitz, Andreas Mügge, Leif Bö;sche, Bernd Lemke
Journal: Journal of the American College of Cardiology (2010)
Activity of a multitargeted chemo-switch regimen (sorafenib, gemcitabine, and metronomic capecitabine) in metastatic renal-cell carcinoma: a phase 2 study (SOGUG-02-06)
Authors: Joaquim Bellmunt, José Manuel Trigo, Emiliano Calvo, Joan Carles, José L Pérez-Gracia, Jordi Rubió, Juan Antonio Virizuela, Rafael López, Martín Lázaro, Joan Albanell
Journal: The Lancet Oncology (2010)
Case of human vibriosis.
Authors: J. H. Darrell, B. C. Farrell, R. A. Mulligan
Journal: BMJ (1967)

MEDICAL JOURNALan attempt to avoid loss of our second strain we froze some aliquots of the original blood cultures at -700 C., and found on later examination that the organisms had survived. SummaryTwo cases of human vibriosis, the first to be recorded in Britain, are described.One of the vibrios isolated was a strict anaerobe, a type not previously recorded as a human pathogen.The condition should be considered whenever a pyrexia of unknown origin is being investigated, and is most likely to be diagnosed if blood cultures are taken.The organisms causing human vibriosis are related to those causing vibriosis in animals and distinct from those causing cholera in man.Non-cholera vibrio infection in man (human vibriosis) may present as a dysentery-like condition or as a pyrexial bacteraemic illness with or without localization of infection.Localization is most likely to occur in the meninges, synovial membranes, valvular endocardium, and, in pregnant women, in the foetus and foetal membranes and placenta.I wish to thank Dr. K. Robson and Dr. T. Pilkington for permission to use their clinical notes and for access to their patients.
Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial
Authors: Katsuyuki Ando, Hiroshi Ohtsu, Shunya Uchida, Shinya Kaname, Yoshihiro Arakawa, Toshiro Fujita
Journal: The Lancet Diabetes & Endocrinology (2014)
New NHS organisations will need dialogue to improve service delivery, meeting hears
Authors: N. Hawkes
Journal: BMJ (2012)

The passage of the Health and Social Care Bill has created a plethora of new structures in England but no certainty that they can exercise enough power either on their own or with others to drive through improvements in service delivery, a breakfast seminar heard this week. 

In the second of a series of King’s Fund breakfast meetings, on 17 July, participants chewed over the role of commissioning—for 20 years the vacant lot between the silos occupied by service purchasers and providers.

Neither Stephen Dorrell, chairman of the parliamentary select committee on health, nor Andrea Young, regional director designate for the south of England for the new NHS Commissioning Board, made any claims that commissioning had in the past really worked as intended. Too often, Dorrell said, it had been experienced as “something done to clinicians by managers, and so long as it feels like that, …
Evaluation of survival data for chronic myelocytic leukemia
Authors: Joseph E. Sokal
Journal: American Journal of Hematology (1976)

Abstract Median survival figures are essentially worthless for evaluation of the effectiveness of therapy in different series of patients with chronic myelocytic leukemia. Such data are heavily influenced by the characteristics of the initial patient mix, which play the major role in determining mortality during the first year of treatment. The effects of differing initial proportions of poor‐risk patients are dissipated within two years, however, and the annual mortality rates thereafter reflect the influence of antileukemic therapy. Comparison of these rates, from very diverse series of patients, yielded quite consistent results and indicated superiority of effective chemotherapy over irradiation or inferior drug schedules.
The Spleen in Osteogenic Sarcoma: A Scan and Autopsy Survey
Authors: RICHARD P. SPENCER, JOHN T. FLANNERY
Journal: Clinical Nuclear Medicine (1977)

Thirty-four cases of osteogenic sarcoma which had been autopsied in Connecticut were studied. Eight of these had associated or related disorders which might have contributed to the sarcoma (four with Paget's disease in the area, two with prior ocular enucleation and irradiation for retinoblastoma, one with a previous mastectomy and external irradiation, and one with a history of working with radium). The weights of 33 spleens which had been recorded were found to be approximately normally distributed. Seven of the spleens contained metastatic osteogenic sarcoma (in five of these cases, the liver also contained metastases). The two largest spleens were not associated with splenic or hepatic metastases or with marked hepatomegaly. The possibility of splenic trapping of immune complexes in osteogenic sarcoma was raised. Of six liver-spleen radiocolloid scans in patients with osteogenic sarcoma, only one had a shift of radiocolloid to the spleen (and the liver was abnormal in that case). Further studies are warranted on the relationship of splenomegaly, shift of radiocolloid to the spleen, or intrasplenic defects, to the clinical course of osteogenic sarcoma and other tumors.
Adoration of the Vagi?
Authors: Jay A. Nadel
Journal: New England Journal of Medicine (1984)

The use of muscarinic antagonists, such as atropine, as bronchodilators has captured the interest of investigators studying the regulation of airway smooth muscle. Cyclic anticholinergic compounds that have recently been developed can be delivered by aerosols into the airways, with minimal systemic side effects. Thus, if acetylcholine released from vagal motor nerves innervating airway smooth muscle is an important cause of airway narrowing in disease, substantial bronchodilation may result, possibly with few side effects (i.e., a high "therapeutic ratio"). For these reasons, it is important therapeutically to determine the efficacy and limitations of the use of muscarinic antagonists.Evidence for . . .
A Specific Role for Saline or the Sodium Ion in the Regulation of Renin and Aldosterone Secretion
Authors: Michael L. Tuck, Robert G. Dluhy, Gordon H. Williams
Journal: Journal of Clinical Investigation (1974)

It is well established that in normal man the renin-angiotensin-aldosterone system is responsive to changes in volume. The present study was performed to determine whether sodium has an action apart from volume in the regulation of the secretion of renin and aldosterone. Acute volume expansion was induced either by saline, dextran, or glucose infusion in supine, normal subjects in balance on a 10 meq sodium/100 meq potassium diet. Plasma renin activity (PRA), angiotensin II (A II), aldosterone (PA), cortisol, serum sodium, and potassium were measured every 10 min for the first 30 min and then at 1, 2, 4, 6, and 8 h.
Anyone for tennis
Authors: Colin Douglas
Journal: BMJ (2001)

Or would you prefer parking? Yes, I think I have a sense of the meeting. No need to go to a vote. Clearly you will be happy to go along with our administrators' plans for the once popular but now somewhat dilapidated tennis courts beyond the former nurses' home …

It must have happened a lot over the decades, all over the NHS. Hospital tennis—a pastime easily compatible with the kind of on-call schedules that persisted into the early 1970s—is now …