tbuckley/cabot-search huggingface dataset:
Use of the Syrian hamster embryo cell transformation assay for carcinogenicity prediction of chemicals currently being tested by the National Toxicology Program in rodent bioassays.
Authors: G A Kerckaert, R Brauninger, R A LeBoeuf, R J Isfort
Journal: Environmental Health Perspectives (1996)

The Syrian hamster embryo (SHE) cell transformation assay was used to predict the carcinogenicity of 26 chemicals currently being tested in the rodent bioassay by the National Toxicology Program as part of its program titled "Strategies for Predicting Chemical Carcinogenesis in Rodents." Of these 26 chemicals, 17 were found to be positive in the SHE cell transformation assay while 9 were negative. Carcinogenicity predictions were made for these chemicals, based upon the SHE cell transformation assay results. Our predictions will be compared with the rodent bioassay results as they become available.
Myocardial thallium-201 kinetics during coronary occlusion and reperfusion: influence of method of reflow and timing of thallium-201 administration.
Authors: J E Granato, D D Watson, T L Flanagan, J A Gascho, G A Beller
Journal: Circulation (1986)

Thallium-201 (201Tl) uptake and redistribution kinetics were examined in an open-chest canine preparation of occlusion and reperfusion. Seven dogs (group I) underwent 3 hr of sustained occlusion and received 1.5 mCi of 201Tl after 40 min of occlusion of the left anterior descending coronary artery (LAD). Group II (n = 18) underwent 60 min of LAD occlusion followed by sudden and total release of the ligature. Group IIa (n = 8) received intravenous 201Tl during occlusion of the LAD, whereas group IIb (n = 10) received intravenous 201Tl at the time of peak reflow. Group III dogs (n = 26) also underwent 60 min of LAD occlusion that was followed by gradual reflow through a residual critical stenosis. Animals in this group also received 201Tl either before (IIIa; n = 16) or after reflow was established (IIIb; n = 10). In group I, the relative 201Tl gradient (nonischemic minus ischemic activity) decreased from 88 +/- 8% (mean +/- SEM) to 59 +/- 6% during 3 hr of coronary occlusion (p = .034). After rapid and total reperfusion (group IIa), this gradient decreased from 71 +/- 6% during occlusion to 26 +/- 5% after reflow (p less than .001). After slow reperfusion through a residual stenosis (group IIIa), the gradient decreased from 81 +/- 5% to 31 +/- 5% (p less than .001) (p = .56 compared with group IIa). In rapidly reperfused dogs receiving intravenous thallium during peak reflow (IIb), initial 201Tl activity in the ischemic zone was 155 +/- 20% of initial normal activity and fell to 93 +/- 13% of normal after 2 hr of reperfusion. Similarly, in dogs reperfused slowly through a critical stenosis (IIIb), which received 201Tl during reflow, 201Tl activity soon after reflow was 94 +/- 4% of initial normal and decreased to 80 +/- 6% at 2 hr of reperfusion (p = .10). Histochemical evidence of necrosis was present in the biopsy region in 80% of the 20 dogs subjected to triphenyl tetrazolium chloride (TTC) staining. Microsphere-determined transmural blood flow was similar in all groups during LAD occlusion and final flows after 2 hr were comparable in all subgroups undergoing reflow. Ischemic zone flow (% normal) was significantly higher at the time of 201Tl administration in groups IIb (192 +/- 25%) and IIIb (110 +/- 5%), which received 201Tl during reflow, than in groups IIa (31 +/- 9%) and IIIa (22 +/- 5%), which received 201Tl during occlusion.(ABSTRACT TRUNCATED AT 400 WORDS)
Hypokalemic Respiratory Arrest in Diabetic Ketoacidosis
Authors: Elisabeth Ryzen
Journal: JAMA (1987)

To the Editor.—  The CASE REPORT entitled Hypokalemic Respiratory Arrest in Diabetic Ketoacidosis 1 emphasizes the importance of adequate potassium repletion in the treatment of patients with diabetic ketoacidosis. However, we were surprised that no mention was made of the need also to assess magnesium concentrations in such patients. Hypomagnesemia is a common finding in diabetics, 2 especially those recovering from diabetic ketoacidosis, 3 and has been reported to cause a decrease in respiratory muscle power. 4 Moreover, refractory hypokalemia, as was seen in the case reported, can be caused by magnesium deficiency. 5 Hypophosphatemia is also commonly associated with hypomagnesemia. 6   Renal losses of magnesium secondary to glycosuria play a primary role in the pathogenesis of magnesium depletion in diabetics. 2 Intravenous fluid therapy during treatment of diabetic ketoacidosis aggravates urinary magnesium losses, and insulin therapy also tends to lower the serum magnesium concentration. 3,7 Less than 1% of
The Use of External Radioactive Markers in Scintimammography
Authors: MARTINE KLEIN, JOLIE WEININGER, SINAIA MOSHE, TAMAR PERETZ, ROLAND CHISIN
Journal: Clinical Nuclear Medicine (2001)

In Tc-99m MIBI scintimammography, the exact localization of foci of increased tracer uptake or the exact anatomic correlation of palpated breast masses with a scintigraphic finding is difficult. The authors describe three patients with known or possible malignant breast lesions for whom the use of external radioactive markers successfully helped to provide this information, thus improving the diagnostic accuracy and guiding decision-making in the patients’ treatment.
Effect of intragastric bile salts on ionic movement across normal human gastric mucosa after intravenous atropine
Authors: K. J. Ivey, L. Denbesten, J. A. Clifton
Journal: Gut (1971)

The effect of intravenous atropine (2.0 mg/70 kg) and intragastric bile salts (5 0-5.5 mM) on ionic fluxes across the gastric mucosa was studied.Serial instillations of bile salts, i n 200 ml 160 m-equiv/l HCl with 51Cr as a non-absorbable indicator, were performed in eight normal subjects.
Intra-Cutaneous Congo Red in Rheumatoid Arthritis
Authors: F. T. Shannon, W. J. Fessel, E. G. L. Bywaters
Journal: Annals of the Rheumatic Diseases (1957)

It has been claimed that, in patients with amyloidosis, the presence of amyloid material in the skin may be demonstrated by the intracutaneous injection of Congo red (Philpott and Freshman, 1936;Nomland, 1936).In the presence of amy- loidosis, the area of staining is said to be more intense and to persist for a longer time than in normal skin.Recently this technique has been employed by Laine, Holopainen, and Makinen (1956) in a series of patients with rheumatoid arthritis.The fixation of the dye in the skin was measured by the time taken for the stained area to fade to a standard intensity and this was found to be significantly longer in 55 patients with rheumatoid arthritis than in thirty normal control subjects.From these results, Laine and his co-workers concluded that this phenomenon might be due to the presence of amyloid in the skin of patients with rheumatoid arthritis.This seemed quite possible since, with the decline of tuberculosis, rheumatoid arthritis is one of the chief causes of secondary amyloid.At the Postgraduate School of Medicine, London, amyloid was found in eight out of 48 autopsied cases (Missen and Taylor, 1956).Using a modified method of assessment, we have confirmed Laine's results, but our experience leads us to differ somewhat from Laine and his colleagues in their tentative conclusions cited above. MethodsAn autoclaved solution of I per cent.Congo red in normal saline was used, since the aqueous solution used by Laine and others was found to produce some pain on injection.This solution may be autoclaved repeatedly without change in its staining properties and no discom- fort or untoward reactions occurred after its injection.A tuberculin syringe was used and exactly 0 1 ml.was injected into the skin of the flexor surface of the forearm of each subject.
Psychosis, Psychopathy, and Homicide: A Preliminary Neuropsychological Inquiry
Authors: Paul G. Nestor, Matthew Kimble, Ileana Berman, Joel Haycock
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study attempted to statistically distinguish subgroups of murderers with mental disorders from among 26 hospitalized men (mean age=34 years) who were committed to a maximum security forensic hospital. METHOD: Measures consisted of objective ratings of psychosis and psychopathy and neuropsychological tests of intelligence, memory and attention, executive functions, and academic abilities. RESULTS: Cluster analysis produced two distinct subgroups: one defined by high incidence of psychosis and low level of psychopathy and one by low incidence of psychosis and high level of psychopathy, each corresponding to distinct neuropsychological differences in intellectual abilities, learning disabilities, and social intelligence. CONCLUSIONS: In light of this relatively small, highly select group, these novel findings must be viewed as preliminary. Studies of larger cohorts are needed before definitive conclusions can be drawn as to the reliability of these two distinct symptom clusters, each independently validated by neuropsychological measures of intelligence, sociality, and academic abilities.
Benjamin Leon Gittelson
Authors: J. Salinsky
Journal: BMJ (2010)

Benjamin Leon Gittelson (“Leon”) was born in London on 12 May 1940. He studied chemistry at St Peter’s College, Oxford (1959-63), and qualified in medicine at University College Hospital, London, in 1970. He died in Cape Town, South Africa on 2 February 2010 from pulmonary fibrosis and cardiac failure.

After postgraduate training at the Maudsley Hospital, London (1970-76), where he qualified with MRCPsych, Leon practised as a specialist psychiatrist and psychotherapist in Cape Town. In the 1980s he developed a …
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Authors: Takeshi Inagaki, Mihwa Choi, Antonio Moschetta, Li Peng, Carolyn L. Cummins, Jeffrey G. McDonald, Guizhen Luo, Stacey A. Jones, Bryan Goodwin, James A. Richardson, Robert D. Gerard, Joyce J. Repa, David J. Mangelsdorf, Steven A. Kliewer
Journal: Cell Metabolism (2005)
Abstract 2942: RKI-1447, a potent ROCK inhibitor with anti-tumor and anti-invasive activities in breast cancer
Authors: Ronil A. Patel, Kara D. Forinash, Roberta Pireddu, Ying Sun, Mathew P. Martin, Jin-Yi Zhu, Brian G. Alexander, Ernst Schonbrunn, Nicholas J. Lawrence, Said M. Sebti
Journal: Cancer Research (2012)

Abstract Rho-associated kinases 1 and 2 (ROCKs) are intimately involved in metastasis and this prompted the development of ROCK inhibitors (RKIs) as anti-metastatic agents. Here, we describe the development of RKI-1447 which inhibits ROCK 1 and 2 potently in vitro (IC50s; 14 and 6 nM, respectively) and suppresses the phosphorylation of ROCK substrates MLC2 and MYPT1 in human breast cancer cells (IC50; 100 nM). The crystal structure of the RKI-1447-ROCK1 complex reveals that RKI-1447 binds the hinge region in the ATP binding site. RKI-1447 is highly selective and does not affect the phosphorylation levels of Akt, Erk, Mek and S6. RKI-1447 is also highly selective at inhibiting ROCK-mediated cytoskeleton re-organization (actin stress fiber formation) following LPA stimulation, but does not affect PKA-meditated lamelipodia and filopodia formation following PDGF and bradykinin stimulation, respectively. RKI-1447 inhibits migration, invasion and anchorage-independent tumor growth of breast cancer cells. A structurally-related analog RKI-1313 that is inactive against ROCKs in vitro (IC50 &amp;gt; 10 µM) has little effects on migration, invasion and anchorage-independent growth. Finally, RKI-1447 is highly effective at inhibiting the growth of ErbB2-driven breast tumors in a transgenic animal model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2942. doi:1538-7445.AM2012-2942
Impact of lenalidomide dose on progression-free survival in patients with relapsed or refractory multiple myeloma
Authors: M A Dimopoulos, M Hussein, A S Swern, D Weber
Journal: Leukemia (2011)

This analysis assessed the effect of lenalidomide on progression-free survival (PFS). Patients with relapsed or refractory multiple myeloma (RRMM) who received lenalidomide plus dexamethasone in the MM-009 and MM-010 trials were pooled and those who had not progressed and were still receiving lenalidomide at 12 months were included. The median follow-up of surviving patients was 48 months. Of 353 patients who received lenalidomide plus dexamethasone, 116 (33%) had not progressed. Overall, 52 patients (45%) had no dose reductions, 25 (22%) had dose reductions ≥12 months and 39 (34%) had dose reductions before 12 months. Patients who had dose reductions ≥12 months had a significantly longer median PFS than those who had reductions before 12 months (P=0.007) or no dose reductions (P=0.039) (not reached vs 28.0 vs 36.8 months, respectively). In a multivariate Cox regression model, dose reduction ≥12 months was an independent predictor of improved PFS (hazard ratio, 0.47; 95% confidence interval, 0.23-0.98) after adjusting for patient characteristics. The data suggest that to achieve maximum PFS benefit, patients with RRMM should be treated for ≥12 months with full-dose lenalidomide plus dexamethasone. Thereafter, patients may benefit from lower-dose continued therapy; prospective studies are needed to confirm these findings.
TCT-153 Safety and efficacy of transendocardial injection of mesenchymal and induced pluripotent stem cells in a swine subacute model of myocardial ischemia
Authors: Ricardo Sanz-Ruiz, Verónica Crisostomo Ayala, Claudia Baez Diaz, Susana Suarez Sancho, Andreu M. Climent, Francisco Miguel Sanchez Margallo, Francisco Fdez-Aviles
Journal: Journal of the American College of Cardiology (2014)
T-cell factor/β-catenin activity is suppressed in two different models of autosomal dominant polycystic kidney disease
Authors: Michelle M. Miller, Diana M. Iglesias, Zhao Zhang, Rachel Corsini, LeeLee Chu, Inga Murawski, Indra Gupta, Stefan Somlo, Gregory G. Germino, Paul R. Goodyer
Journal: Kidney International (2011)
Terminal acute myelogenous leukemia in a patient with congenital agranulocytosis
Authors: Wing‐Yen Wong, Donald Williams, Marilyn L. Slovak, Bishan Charak, Amitabha Mazumder, David Snyder, Darleen R. Powars, Russell K. Brynes
Journal: American Journal of Hematology (1993)

Congenital agranulocytosis terminating in acute myelogenous leukemia has been previously reported in only two cases of adolescent males. We describe the clinical and laboratory features of a 13-year-old male with congenital agranulocytosis, treated with G-CSF with initial good neutrophil response, who subsequently developed acute myeloid leukemia. This rare complication may define a preleukemic subset of patients for whom G-CSF therapy is ineffective. The diagnostic challenges of this case are presented.
The Chemotherapy of Hypertension
Authors: Edward D. Freis
Journal: JAMA (1971)

It was by chance that I became involved in 1946 in the clinical evaluation of antihypertensive agents. After World War II, I had returned to Boston to complete my residency training in internal medicine and to work in hemodynamics research with Robert Wilkins at the Massachusetts Memorial Hospital. Surgical sympathectomy was then the popular method for treating hypertension and Dr. Wilkins was involved with Reginald Smithwick in assessing the cardiovascular and circulatory changes associated with this operative procedure. However, Dr. Wilkins and Chester Keefer had been asked by James Shannon, who was then director of the Squibb Institute for Medical Research, to work with the Institute in exploring the possibility of developing a successful chemotherapy for hypertension. The clinical evaluation of any drugs that might emerge in this project was assigned to me working under the direction of Dr. Wilkins. The first drug tested was an outgrowth of the World
Mortality Associated With Atrial Fibrillation in Patients With Myocardial Infarction
Authors: Patricia Jabre, Véronique L. Roger, Mohammad H. Murad, Alanna M. Chamberlain, Larry Prokop, Frédéric Adnet, Xavier Jouven
Journal: Circulation (2011)

Atrial fibrillation (AF) is a common finding in patients with myocardial infarction (MI). Atrial fibrillation is not generally perceived by clinicians as a critical event during the acute phase of MI; however, its prognostic influence in MI remains controversial. Furthermore, contradictory data exist concerning the risk of death according to AF timing. This article, a systematic review and first meta-analysis, aims to quantify the mortality risk associated with AF in MI patients and its timing.A comprehensive search of several electronic databases (1970 to 2010; adults, any language) identified MI studies that evaluated mortality related to AF. Evidence was reviewed by 2 blinded reviewers with a formal assessment of the methodological quality of the studies. Adjusted odds ratios were pooled across studies using the random-effects model. The I(2) statistic was used to assess heterogeneity. In the 43 included studies (278 854 subjects), the mortality odds ratio associated with AF was 1.46 (95% confidence interval, 1.35 to 1.58; I(2)=76%; 23 studies). This worse prognosis persisted regardless of the timing of AF; the odds ratio of mortality for new AF with no prior history of AF was 1.37 (95% confidence interval, 1.26 to 1.49), I(2)=28%, 9 studies), and for prior AF was 1.28 (95% confidence interval, 1.16 to 1.40; I(2)=24%; 4 studies). The sensitivity analysis of new AF studies adjusting for confounding factors did not show a decrease in risk of death.Atrial fibrillation is associated with increased risk of mortality in MI patients. New AF with no history of AF before MI remained associated with an increased risk of mortality even after adjustment for several important AF risk factors. These subsequent increases in mortality suggest that AF can no longer be considered a nonsevere event during MI.
Government simplifies warnings on air pollution
Authors: H. Barratt
Journal: BMJ (2001)

People with asthma and other lung diseases are to benefit from a much simpler system of air quality forecasts, the UK government has announced.

The Department for the Environment, Food and Rural Affairs hopes that the changes will make it easier for potentially vulnerable people to take precautions when air quality is poor, as well as encouraging the public to work towards improving air …
Microsatellites, transposable elements and the X chromosome
Authors: P. Jarne, P. David, F. Viard
Journal: Molecular Biology and Evolution (1998)

Variability at microsatellite (MS) loci is generally perceived as resulting from an interaction between mutation and genetic drift and, to a lesser extent, selection and recombination. Less investigated has been the reason for MS accumulation in genomes. We present here a simple model that could account for the variation in density of MS loci, assuming that they are created either through replication slippage or in association with transposable elements. Microsatellites then evolve under the forces cited above. We use this framework to revisit two results obtained from high-density genomic maps of the human and mouse genomes built with thousands of CA repeats: MS loci are (1) less variable and (2) less dense on the X chromosome than on autosomes. The first result is most likely explained by differential mutation on the X chromosome and the autosomes. The second result may be explained by differential mutation, provided the distributions of MS loci are still not at equilibrium. Selection, acting either directly on large allele size or indirectly on the transposable elements associated with MS, may explain the same result. The framework developed here is a first step toward more rigorous models, calling for additional data.
General health checks may work
Authors: T. Lauritzen, A. Sandbaek, K. Borch-Johnsen
Journal: BMJ (2014)

We disagree with Gotzsche and colleagues’ conclusion that general health checks don’t work,1 which is based on their Cochrane review and the recent Inter99 publication.2 The Cochrane review included older trials and thus tested outdated screening tests and treatments. A recent meta-analysis of general practice based health checks found small improvements in surrogate outcomes, especially in high risk patients.3 The Inter99 …
Exercise-induced Asthma
Authors: Miles Weinberger
Journal: JAMA (1976)

<h3>To the Editor.—</h3> Bierman et al (234: 295,1975) suggest that ephedrine and theophylline in combination have an additive effect in suppressing exercise-induced bronchospasm. On examination of these data, however, I am more impressed with the relative lack of suppression of exercise-induced bronchospasm that was obtained even with the combination product. It certainly does not compare with the far more impressive blocking of exercise-induced bronchospasm that can be achieved with an inhaled sympathomimetic amine<sup>1</sup>or with theophylline administered in doses that achieve therapeutic serum concentrations of 10μg/ml to 20μg/ml.<sup>2</sup> The data of Bierman et al demonstrate mild bronchodilation (an 11% increase in the forced expiratory flow (FEF) 25% to 75%) during the preexercise period after the administration of a theophylline-ephedrinehydroxyzine hydrochloride mixture had been followed by a 19% postexercise drop in the FEF<sub>25%-75%</sub>. By comparison, exercise resulted in only a 25% fall in FEF<sub>25%-75%</sub>after the administration
729. Phase I Trial of Intraperitoneal (IP) Administration of a Measles Virus (MV) Strain Expressing the Human Carcinoembryonic Antigen (CEA) in Ovarian Cancer Patients
Authors: Evanthia Galanis, Lynn C. Hartmann, William A. Cliby, Paula Zollman, Prema P. Peethambaram, Harry J. Long, Judith S. Kaur, Jeff A. Sloan, Gregory A. Poland, Kah-Whye Peng, Stephen J. Russell
Journal: Molecular Therapy (2006)

Top of pageAbstract
Background: Edmonston vaccine strains of MV have significant antitumor activity against ovarian cancer xenografts (Peng et al, Cancer Res, 2002). Oncolytic selectivity is due to overexpression of the MV CD46 receptor in ovarian cancer cells. Furthermore, engineering the virus to express the marker peptide CEA (MV-CEA) allows real time monitoring of viral gene expression/ propagation in vivo.

Methods: We are conducting a Phase I trial of MV-CEA in patients (pts) with recurrent, taxol and platinum refractory ovarian or primary peritoneal carcinoma. Eligible pts should have protective anti-MV antibody (ab) titers and normal CEA levels. A standard phase I cohorts of three statistical design is employed. MV-CEA is administered IP via a port-a-cath, q 4 wks for up to 6 cycles.

Results: To date, 12 pts have received viral doses from 103 to 106 TCID50. No dose-limiting toxicity has been observed. Most common toxicities included grade 1|[ndash]|2 nausea (4 pts); grade 1|[ndash]|2 fatigue (4 pts); grade 1 fever (3 pts); grade 1 abdominal pain (2 pts). One pt had grade 1|[ndash]|3 arthralgias in cycles 4|[ndash]|6. There was no treatment induced immunosuppression as assessed by DTH, CD4, CD8, immunoglobulin and complement levels, no significant increase in the titers of anti-MV abs in serum or ascites in response to treatment, and no development of anti-CEA abs. Viral genomes were detected in the peripheral blood mononuclear cells of 2 asymptomatic pts by QRT-PCR. No CEA elevation in the serum was observed in the dose range tested, and there was no viral shedding in urine or mouth gargle specimens. Testing of pt tumor samples for CD46 by IHC demonstrated overexpression of the target receptor in 7/8 pts. Best objective response was stable disease (2|[ndash]|8 mo duration) in 5 pts, while 3 pts had significant decrease in CA125 levels, of 44%, 72%, and 78%, respectively.

Conclusions: In this first human application of an engineered oncolytic MV strain, we have observed excellent tolerance after repeat IP administration of the virus. Despite the low doses employed so far, there is early evidence of biologic activity. Dose escalation continues to the target dose of 109 TCID50.