tbuckley/cabot-search huggingface dataset:
In situ microscopic analysis of asbestos and synthetic vitreous fibers retained in hamster lungs following inhalation.
Authors: R A Rogers, J M Antonini, H Brismar, J Lai, T W Hesterberg, E H Oldmixon, P Thevenaz, J D Brain
Journal: Environmental Health Perspectives (1999)

Hamsters breathed, nose-only, for 13 weeks, 5 days/week, 6 hr/day, either man-made vitreous fiber (MMVF)10a, MMVF33, or long amosite asbestos at approximately 300 World Health Organization (WHO) fibers/cc or long amosite at 25 WHO fibers/cc. [World Health Organization fibers are longer than 5 microm and thicker than 3 microm, with aspect ratio >3.] After sacrifice, fiber burden was estimated (left lungs) by ashing and scanning electron microscopy (ashing/SEM) or (right middle lobes) by confocal laser scanning microscopy (CLSM) in situ. In situ CLSM also provided three-dimensional views of fibers retained, undisturbed, in lung tissue. Fibers of each type were lodged in alveoli and small airways, especially at airway bifurcations, and were seen fully or partly engulfed by alveolar macrophages. Amosite fibers penetrated into and through alveolar septa. Length densities of fibers in parenchyma (total length of fiber per unit volume of lung) were estimated stereologically from fiber transsections counted on two-dimensional optical sections and were 30.5, 25.3, 20.0, and 81.6 mm/mm3 for MMVF10a, MMVF33, and low- and high-dose amosite, respectively. Lengths of individual fibers were measured in three dimensions by tracking individual fibers through series of optical sections. Length distributions of amosite fibers aerosolized, but before inhalation versus after retention in the lung were similar, whether determined by ashing/SEM or in situ CLSM. In contrast, the fraction of short MMVF10a and MMVF33 fibers increased and the geometric mean fiber lengths of both MMVFs decreased by approximately 60% during retention. Most likely due to fiber deposition pattern and differences in sampling, fiber burdens [MMVF10a, MMVF33, and amosite (high dose; 269 WHO fibers/cc)] determined by ashing/SEM were 1.4, 1. 5, and 3.5 times greater, respectively, than those calculated from in situ CLSM data. In situ CLSM is able to provide detailed information about the anatomic sites of fiber retention and also fiber lengths and burdens in good agreement with ashing/SEM results.
Five-Year Results of a Randomized Clinical Trial Comparing Total Mastectomy and Segmental Mastectomy with or without Radiation in the Treatment of Breast Cancer
Authors: Bernard Fisher, Madeline Bauer, Richard Margolese, Roger Poisson, Yosef Pilch, Carol Redmond, Edwin Fisher, Norman Wolmark, Melvin Deutsch, Eleanor Montague, Elizabeth Saffer, Lawrence Wickerham, Harvey Lerner, Andrew Glass, Henry Shibata, Peter Deckers, Alfred Ketcham, Robert Oishi, Ian Russell
Journal: New England Journal of Medicine (1985)

In 1976 we began a randomized trial to evaluate breast conservation by a segmental mastectomy in the treatment of Stage I and II breast tumors ≤4 cm in size. The operation removes only sufficient tissue to ensure that margins of resected specimens are free of tumor. Women were randomly assigned to total mastectomy, segmental mastectomy alone, or segmental mastectomy followed by breast irradiation. All patients had axillary dissections, and patients with positive nodes received chemotherapy. Life-table estimates based on data from 1843 women indicated that treatment by segmental mastectomy, with or without breast irradiation, resulted in disease-free, distant-disease–free, and overall survival at five years that was no worse than that after total breast removal. In fact, disease-free survival after segmental mastectomy plus radiation was better than disease-free survival after total mastectomy (P = 0.04), and overall survival after segmental mastectomy, with or without radiation, was better than overall survival after total mastectomy (P = 0.07, and 0.06, respectively). A total of 92.3 per cent of women treated with radiation remained free of breast tumor at five years, as compared with 72.1 per cent of those receiving no radiation (P<0.001). Among patients with positive nodes 97.9 per cent of women treated with radiation and 63.8 per cent of those receiving no radiation remained tumor-free (P<0.001), although both groups received chemotherapy. We conclude that segmental mastectomy, followed by breast irradiation in all patients and adjuvant chemotherapy in women with positive nodes, is appropriate therapy for Stage I and II breast tumors ≤4 cm, provided that margins of resected specimens are free of tumor. (N Engl J Med 1985; 312:665–73.)
Conference attacks referral centres
Authors: Zosia Kmietowicz
Journal: BMJ (2006)

Doctors have criticised referral management centres for sending patients for inappropriate treatment to independent sector treatment centres far from their home. At their annual conference in Belfast, BMA representatives backed motions that condemned the use of referral management centres, saying they made a nonsense of patient choice, and called for a restoration of GPs' right to refer patients to a named specialist.

Charlie Daniels, a GP in …
Gianotti-Crosti Syndrome
Authors: Ferdinando Gianotti
Journal: British Journal of Dermatology (1968)

Journal Article Gianotti‐Crosti Syndrome Get access Ferdinando Gianotti Ferdinando Gianotti Clinica Dermatologica, Via Pace 9, Milan, Italy Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 5, 1 May 1968, Page 342, https://doi.org/10.1111/j.1365-2133.1968.tb12312.x Published: 01 May 1968
Finding the Causes of Birth Defects
Authors: Jose F. Cordero
Journal: New England Journal of Medicine (1994)

Birth defects are the leading cause of infant mortality, and they account for much of the disability in children in the United States and most developed countries1,2. To reduce infant mortality we must find the causes of birth defects and implement strategies to prevent them. There has been great progress in finding and preventing some birth defects, such as congenital rubella, yet in the United States more than 150,000 babies are born each year with serious birth defects. Some causes of birth defects have been identified in the past 40 years -- human teratogens, chromosomal defects, and single-gene . . .
Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors
Authors: Yenan T. Bryceson, Hans-Gustaf Ljunggren, Eric O. Long
Journal: Blood (2009)

Natural killer (NK) cells provide innate control of infected and neoplastic cells. Multiple receptors have been implicated in natural cytotoxicity, but their individual contribution remains unclear. Here, we studied the activation of primary, resting human NK cells by Drosophila cells expressing ligands for receptors NKG2D, DNAM-1, 2B4, CD2, and LFA-1. Each receptor was capable of inducing inside-out signals for LFA-1, promoting adhesion, but none induced degranulation. Rather, release of cytolytic granules required synergistic activation through coengagement of receptors, shown here for NKG2D and 2B4. Although engagement of NKG2D and 2B4 was not sufficient for strong target cell lysis, collective engagement of LFA-1, NKG2D, and 2B4 defined a minimal requirement for natural cytotoxicity. Remarkably, inside-out signaling induced by each one of these receptors, including LFA-1, was inhibited by receptor CD94/NKG2A binding to HLA-E. Strong inside-out signals induced by the combination of NKG2D and 2B4 or by CD16 could overcome CD94/NKG2A inhibition. In contrast, degranulation induced by these receptors was still subject to inhibition by CD94/NKG2A. These results reveal multiple layers in the activation pathway for natural cytotoxicity and that steps as distinct as inside-out signaling to LFA-1 and signals for granule release are sensitive to inhibition by CD94/NKG2A.
SELECTIVE VAGOTOMY IN THE PREVENTION OF POST-VAGOTOMY DIARRHŒA
Authors: H.W. Burge, A.R. Rizk, A.M.B. Tompkin, C.E. Barth, J.S.F. Hutchison, C.J. Longland, I. Mclennan, D.C. Miln
Journal: The Lancet (1961)
Injuries to pedestrians in road traffic accidents.
Authors: R. M. Atkins, W. H. Turner, R. B. Duthie, B. R. Wilde
Journal: BMJ (1988)

Although there have been many reports on injuries to occupants of cars in road traffic accidents, there have been few prospective studies of injuries to pedestrians in such accidents. For this reason a two year prospective study of pedestrians in road traffic accidents in the Oxford region was carried out. The incidence of death in pedestrians was significantly higher than in car occupants or motorcyclists. The principal determinant of death was the weight of the vehicle concerned. The most common site of injury was the head because of a high incidence of brief concussion, but the most common site of serious injuries was the leg. Injuries to all regions of the body increased with age and with the weight of the vehicle in the collision. Accidents most often concerned young children or the elderly.
Early Colorectal Cancer - Follow-up after Endoscopic Polypectomy
Authors: A.H. Speroni, R.P. Meiss, C. Calzona, R.H. Castelletto, A. Jmelnitzky, N. Chopita, C.M. Vaccarezza, H.H. Rubio
Journal: Endoscopy (1988)

Approximately 90% of correctly indicated endoscopic polypectomies for early colorectal cancer, whether invasive or not, are curative, provided strict criteria are adopted in the pathological evaluation of the resected specimen. Unrestricted time surveillance is mandatory since benign (more frequent) or malignant relapses appear in 30-40% of the patients.
Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis
Authors: Tomohiro Watanabe, Naoki Asano, Peter J. Murray, Keiko Ozato, Prafullakumar Tailor, Ivan J. Fuss, Atsushi Kitani, Warren Strober
Journal: Journal of Clinical Investigation (2008)

The mechanisms underlying the susceptibility of individuals with caspase recruitment domain 15 (CARD15) mutations and corresponding abnormalities of nucleotide-binding oligomerization domain 2 (NOD2) protein to Crohn disease are still poorly understood. One possibility is based on previous studies showing that muramyl dipeptide (MDP) activation of NOD2 negatively regulates TLR2 responses and that absence of such regulation leads to heightened Th1 responses. We now report that administration of MDP protects mice from the development of experimental colitis by downregulating multiple TLR responses, not just TLR2. The basis of these in vivo findings was suggested by in vitro studies of DCs, in which we showed that prestimulation of cells with MDP reduces cytokine responses to multiple TLR ligands and this reduction is dependent on enhanced IFN regulatory factor 4 (IRF4) activity. Further studies of mouse models of colitis showed that this inhibitory role of IRF4 does in fact apply to MDP-mediated protection from colitis, since neither IRF4-deficient mice nor mice treated with siRNA specific for IRF4 were protected. These findings indicate that MDP activation of NOD2 regulates innate responses to intestinal microflora by downregulating multiple TLR responses and suggest that the absence of such regulation leads to increased susceptibility to Crohn disease.
Molecular Pathways: Microsatellite Instability in Colorectal Cancer: Prognostic, Predictive, and Therapeutic Implications
Authors: Frank A. Sinicrope, Daniel J. Sargent
Journal: Clinical Cancer Research (2012)

Abstract Microsatellite instability (MSI) is the molecular fingerprint of the deficient mismatch repair (MMR) system, which characterizes ∼15% of colorectal cancers. MSI develops as a result of germline mutations in MMR genes or, more commonly, from epigenetic silencing of MLH1 in sporadic tumors occurring in a background of methylation of CpG islands in gene promoter regions and in tumors that frequently show hotspot mutations in the BRAF oncogene. MSI tumors have distinct phenotypic features and have been consistently associated with a better stage-adjusted prognosis compared with microsatellite stable tumors. MSI negatively predicts response to 5-fluorouracil and may also determine responsiveness to other drugs used for treatment of colorectal cancers. Recent data have expanded the molecular heterogeneity of MSI tumors and may contribute to our understanding of differential chemosensitivity. The ability to identify deficient MMR has important implications for patient management, and it holds promise for therapeutic exploitation and for the development of novel therapeutics. Clin Cancer Res; 18(6); 1506–12. ©2012 AACR.
USE OF INTRA-AORTIC AND INTRACARDIAC TRANSFUSIONS IN CARDIAC ARREST
Authors: Hugh E. Stephenson
Journal: JAMA (1953)

When cardiac arrest or sudden shock occurs in the operating room, the problem of rapid transfusion of whole blood is often of paramount urgency. Much has been written about the efficacy of intra-arterial transfusions in selected cases. The intra-aortic and intra-cardiac routes, however, have not received adequate attention. It is the purpose of this report to consider these routes. <h3>INTRA-AORTIC TRANSFUSION</h3> A recent case illustrates the use of the intra-aortic transfusion route. <h3>Case 1.</h3> —The patient, a 36-year-old Negro man, was admitted with massive hematemesis and melana of several hours' duration. There was a history of proved duodenal ulcer that had been demonstrated rontgenographically and for which the patient had been under conservative therapy. Despite repeated transfusions and insertion of a Sengstaken tube, bleeding continued, and a subtotal gastrectomy was thought advisable. At operation, 36 hours after the patient's admission, exploration of the abdomen revealed a large, penetrating, posterior ulcer
Selective enhancement of function of stunned myocardium by increased flow.
Authors: L D Stahl, T R Aversano, L C Becker
Journal: Circulation (1986)

Although augmentation of flow does not improve the performance of normal myocardium, the hyperemic response after brief coronary occlusion is associated with transient hyperfunction in the previously ischemic region. In this study we assessed the effect of vasodilator-enhanced coronary blood flow on the systolic function of postischemic stunned myocardium. In 18 open-chest, anesthetized dogs the anterior descending artery was occluded for 5 min, followed by a 10 min period of reflow, repeated 12 times with a final 90 min recovery period. After the recovery period, either 0.06 mg/min dipyridamole (n = 6), 1 mg/min papaverine (n = 6), or 1.5 micrograms/kg/min nitroglycerin (n = 6) was infused intravenously for 15 min. Regional myocardial blood flow, which had returned to normal before administration of vasodilator, was increased 150% above baseline by dipyridamole and 80% by papaverine, but was unchanged by nitroglycerin. Segmental shortening decreased after repeated occlusions: from 17.5% to 0.9% in the group later treated with dipyridamole, from 18.6% to 6.7% in the papaverine group, and from 19.2% to-1.9% in the nitroglycerin group (p less than .005 for all groups). Segmental shortening increased to 8.8% after dipyridamole, 13.6% after papaverine, and 5.1% after nitroglycerin (p less than .05 for all groups), although the load-independent end-systolic pressure-length relationship (ESPLR) showed a significant shift to the left, reflecting enhanced performance, only after dipyridamole and papaverine. For all dogs combined, the percent improvement in ESPLR was correlated with the percent increase in flow (R = -.73, p less than .001). Performance was unchanged in the control region despite similar augmentation of flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Case of cronkhite--Canada syndrome with associated jejunal diverticulosis.
Authors: W J Cunliffe, J Anderson
Journal: BMJ (1967)

The association of gastrointestinal polypi with diffuse alopecia and nail dystrophy was first recorded by Cronkhite and Canada (1955).This paper records the ninth patient with this syndrome. CASE REPORTThe patient was a schoolmaster aged 60.In 1957 diffuse alopecia and " unusual nails " were noted during investigations for dyspepsia.Laparotomy revealed a nodular pancreas, and chronic pancreatitis
BCR-ABL SH3-SH2 domain mutations in chronic myeloid leukemia patients on imatinib
Authors: Daniel W. Sherbenou, Oliver Hantschel, Ines Kaupe, Stephanie Willis, Thomas Bumm, Lalita P. Turaga, Thoralf Lange, Kim-Hien Dao, Richard D. Press, Brian J. Druker, Giulio Superti-Furga, Michael W. Deininger
Journal: Blood (2010)
Asthma and Wheezing in Young Children
Authors: Michael Silverman
Journal: New England Journal of Medicine (1995)

Asthma might seem to be a single, easily recognizable disorder. At the margins, perhaps, chronic obstructive pulmonary disease and the gray zone of very mild disease can create diagnostic difficulty, but the central ground is no longer problematic. Or so it has seemed. The article by Martinez and his colleagues from Tucson, Arizona, in this issue of the Journal challenges this complacent view.1 Although they describe a study of wheezing disorders in young children, I believe that the authors' main conclusion, that there are several distinct groups of people among those who wheeze, will soon be shown to apply to . . .
Expression and localization of heat shock proteins in rat basophilic leukemia cells: differential modulation by degranulation, thermal or oxidative stress
Authors: M. Bachelet, F. Marchand, E. Souil, D. François, E. Mariéthoz, A. Weyer, B. S. Polla
Journal: Allergy (2002)

Rat basophilic leukemia (RBL-2H3) cells are well characterized in terms of morphological and biochemical changes upon activation, and have been extensively used as a model system for studying the mechanisms of the immediate hypersensitivity reaction. To investigate whether overexpression of heat shock/stress proteins (HSP) is involved in the mast cell-dependent reactivity, we examined the adaptive responses of RBL-2H3 cells to classical stress conditions such as heat shock or oxidative injury produced by an aqueous extract of tobacco smoke.HSP were determined by flow cytometry and immunocytochemistry. Degranulation was confirmed as the release of beta-hexosaminidase, determined spectrophotometrically, and by electron microscopy experiments.We found that RBL-2H3 cells respond to heat shock or oxidative injury by the synthesis of both the inducible 72 kDa HSP (Hsp70), and the oxidation-specific 32 kDa heme oxygenase (HO)-1. Heat shock induced mainly Hsp70 in a cell growth-dependent manner, whereas oxidative stress induced mainly HO-1 in a cell growth-independent manner. However, heat shock or oxidative stress had no significant effects on degranulation.Stress-mediated synthesis of HSP was not associated with RBL-2H3 degranulation and likewise, degranulation did not induce HSP.
Cognitive Performance in Late Adolescence and the Subsequent Risk of Subdural Hematoma: An Observational Study of a Prospective Nationwide Cohort
Authors: Anna Nordström, Peter Nordström
Journal: PLoS Medicine (2011)

Anna and Peter Nordström analyzed a prospective nationwide cohort of 440,742 Swedish men and found that reduced cognitive function in young adulthood was associated with increased risk of subdural hematoma later in life, whereas a higher level of education and physical fitness were associated with a decreased risk.
Renal transplantation in diabetics nephropathy.
Authors: M Gonzalez-Carrillo, A Moloney, M Bewick, V Parsons, C J Rudge, P J Watkins
Journal: BMJ (1982)

Forty diabetics who had developed end-stage renal failure from diabetic nephropathy and underwent renal transplantation have been followed up from one to six years. After one and two years 63% and 42% survived (45% and 33% respectively with functioning kidneys). Older patients, those with coronary and peripheral vascular disease, and those with severe neuropathy are prone to higher postoperative morbidity and mortality. The presence of advanced retinopathy, on the other hand, does not appear to influence the outcome.
Responses of young girls to two modes of aerobic training.
Authors: J R Welsman, N Armstrong, S Withers
Journal: British Journal of Sports Medicine (1997)

OBJECTIVES: To investigate the physiological effects of two different three times a week, eight week training programmes on the aerobic fitness of nine to ten year old girls. METHODS: Treadmill determined peak VO2, submaximal heart rates, and submaximal blood lactate were the criterion measures. Seventeen girls completed a programme of "aerobics" training where sessions lasted 20-25 minutes. Eighteen girls followed a cycle ergometer training programme which involved pedalling continuously for 20 minutes with the heart rate maintained between 160 and 170 beats/minute. A control group of 16 girls completed the criterion tests but did not train. In the cycle ergometer group and eight control subjects plasma total cholesterol and high density lipoprotein cholesterol were determined before and after training. RESULTS: Peak VO2 did not change significantly with training in either training group, neither were there any significant changes in submaximal heart rates. Blood lactate declined significantly at the two lowest submaximal exercise intensities in the cycle ergometer training group (from 2.3 (1.1) to 1.4 (0.06) mmol/l at stage 1 and from 2.1 (1.2) to 1.6 (0.06) mmol/l at stage 2; means (SD); P &lt; 0.01). Total cholesterol and high density lipoprotein cholesterol remained unchanged with training. CONCLUSIONS: These findings suggest that an eight week structured exercise programme produces minimal changes in either the aerobic fitness or blood lipids of young girls. It may be more beneficial for long term health to promote enjoyment in activity and positive attitudes to exercise rather than attempting to enhance aerobic fitness through strenuous exercise programmes.
The Identification of (ETV6)/RUNX1-Regulated Genes in Lymphopoiesis Using Histone Deacetylase Inhibitors in ETV6/RUNX1-Positive Lymphoid Leukemic Cells
Authors: Julia Starkova, Jozef Madzo, Gunnar Cario, Tomas Kalina, Anthony Ford, Marketa Zaliova, Ondrej Hrusak, Jan Trka
Journal: Clinical Cancer Research (2007)

Chimeric transcription factor ETV6/RUNX1 (TEL/AML1) is believed to cause pathologic block in lymphoid cell development via interaction with corepressor complex and histone deacetylase. We wanted to show the regulatory effect of ETV6/RUNX1 and its reversibility by histone deacetylase inhibitors (HDACi), as well as to identify potential ETV6/RUNX1-regulated genes.We used luciferase assay to show the interaction of ETV6/RUNX1 protein, ETV6/RUNX1-regulated gene, and HDACi. To identify ETV6/RUNX1-regulated genes, we used expression profiling and HDACi in lymphoid cells. Next, using the flow cytometry and quantitative reverse transcription-PCR, we measured differentiation changes in gene and protein expression after HDACi treatment.Luciferase assay showed repression of granzyme B expression by ETV6/RUNX1 protein and the reversibility of this effect by HDACi. Proving this regulatory role of ETV6/RUNX1, we identified, using complex statistical analysis, 25 genes that are potentially regulated by ETV6/RUNX1 protein. In four selected genes with known role in the cell cycle regulation (JunD, ACK1, PDGFRB, and TCF4), we confirmed expression changes after HDACi by quantitative analysis. After HDACi treatment, ETV6/RUNX1-positive cells showed immunophenotype changes resembling differentiation process compared with other leukemic cells (BCR/ABL, ETV6/PDGFRB positive). Moreover, ETV6/RUNX1-positive leukemic cells accumulated in G(1)-G(0) phase after HDACi whereas other B-lineage leukemic cell lines showed rather unspecific changes including induction of apoptosis and decreased proliferation.Presented data support the hypothesis that HDACi affect ETV6/RUNX1-positive cells via direct interaction with ETV6/RUNX1 protein and that treatment with HDACi may release aberrant transcription activity caused by ETV6/RUNX1 chimeric transcription factor.