tbuckley/cabot-search huggingface dataset:
Abstract IA15: Context-specific oncogenesis by ETS-family transcription factors
Authors: Yu Chen, Shipra Shukla, Ping Chi, Brett Carver, Charles L. Sawyers
Journal: Cancer Research (2012)

Abstract Recurrent translocation involving ETS-family transcription factors including ERG and ETV1, ETV4, and ETV5 occur in over half of prostate cancers, implicating them as driver oncogenes in prostate tumorigenesis. Two observations pose important questions. 1) The same ETS factors aberrantly expressed in prostate cancer can be endogenously highly expressed in other tissues to modulate normal physiology (e.g., ERG expression in endothelial cells and ETV1 expression in neurons). 2) Forced overexpression in prostate model systems such as immortalized human primary prostate epithelial cells and mouse prostate yields minimal phenotype. These observations indicate that ETS mediated oncogenesis is highly dependent on the cellular context, which is mediated by the cell/tissue type and cooperating lesions. We asked how cellular context affects the DNA binding, transcriptional output, and phenotype of ETS proteins. We compared human ETS dependent tumor cell lines from two lineages, prostate cancer and gastrointestinal stromal tumor and show that ETS binding is largely tissue specific. Further, we have generated genetically engineered mouse models that express ETS in different tissues, within different compartments of the prostate gland, and with different cooperating lesions. We show that ERG binding to genomic DNA is largely similar in PTEN intact and PTEN null mouse prostates. Yet, ERG can only mediate a transcriptional program that mediates an aggressive phenotype in PTEN null prostates. These data suggests that cellular context is critical for ETS transcription factor function. Citation Format: Yu Chen, Shipra Shukla, Ping Chi, Brett Carver, Charles L. Sawyers. Context-specific oncogenesis by ETS-family transcription factors [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr IA15.
THE PHOSPHATASE CONTENT OF THE BLOOD SERUM IN JAUNDICE 1
Authors: Carl H. Greene, Howard F. Shattuck, Lillian Kaplowitz
Journal: Journal of Clinical Investigation (1934)

Enzymes which hydrolyze esters of phosphoric acid, phosphatases, are found in many mammalian tissues.Robison (9) has stressed the pres- ence of these enzymes in growing bone and their importance in relation to the processes of calcification and bone development.Further evidence of the importance of this enzyme in the metabolism of bone (6) was ad- duced with the discovery that the phosphatase content of the blood serum was increased in various diseases such as rickets, Paget's disease or hyper- parathyroidism in which osseous changes are marked.In these conditions the increase in the serum or plasma phosphatase apparently is secondary to the osseous lesions.Phosphatases are present in many tissues and occur in greatest amount in the intestinal mucosa and the kidney.Smaller amounts have been re- ported in the liver and in the bile (4).Bodansky and Jaffe (2, 3) have found that in normal individuals the phosphatase content of the serum varies with digestive activity and so postulate that while some of the phosphatase in the serum may be osseous in origin some at least is non- osseous.This is also true in some pathological conditions for Rob- erts (7, 8) who was one of the first to study the changes in the phosphatase content of the serum in disease, reported that high values were present in cases of obstructive jaundice whereas in catarrhal jaundice the value was only slightly increased over the normal.Roberts (8) considered this difference to be sufficiently marked to be of diagnostic value in the differ- entiation of the several types of jaundice.Bodansky and Jaffe (2) con- firmed the increase in the serum phosphatase in jaundice but their results cast doubt on the diagnostic value of the test for they reported a series of nine cases of catarrhal jaundice and hepatitis in which elevated readings were obtained. METHODS AND MATERIALSUsing the method of Bodansky (1) we have studied the phosphatase content of the serum in a series of 40 cases of jaundice of various types.
The Notch ligand DLL4 specifically marks human hematoendothelial progenitors and regulates their hematopoietic fate
Authors: V Ayllón, C Bueno, V Ramos-Mejía, O Navarro-Montero, C Prieto, P J Real, T Romero, M J García-León, M L Toribio, A Bigas, P Menendez
Journal: Leukemia (2015)
Does Breast-Feeding in Infancy Lower Blood Pressure in Childhood?
Authors: Richard M. Martin, Andrew R. Ness, David Gunnell, Pauline Emmett, George Davey Smith
Journal: Circulation (2004)

Breast-feeding in infancy has been associated with decreased coronary heart disease mortality, but the underlying mechanisms are unclear. We investigated the association of breast-feeding with blood pressure in a contemporary cohort.In a prospective cohort study (ALSPAC, United Kingdom), a total of 7276 singleton, term infants born in 1991 and 1992 were examined at 7.5 years. Complete data were available for 4763 children. The systolic and diastolic blood pressures of breast-fed children were 1.2 mm Hg lower (95% CI, 0.5 to 1.9) and 0.9 mm Hg lower (0.3 to 1.4), respectively, compared with children who were never breast-fed (models controlled for age, sex, room temperature, and field observer). Blood pressure differences were attenuated but remained statistically significant in fully adjusted models controlling for social, economic, maternal, and anthropometric variables (reduction in systolic blood pressure: 0.8 mm Hg [0.1 to 1.5]; reduction in diastolic blood pressure: 0.6 mm Hg [0.1 to 1.0]). Blood pressure differences were similar whether breast-feeding was partial or exclusive. We examined the effect of breast-feeding duration. In fully adjusted models, there was a 0.2-mm Hg reduction (0.0 to 0.3) in systolic pressure for each 3 months of breast-feeding.Breast-feeding is associated with a lowering of later blood pressure in children born at term. If the association is causal, the wider promotion of breast-feeding is a potential component of the public health strategy to reduce population levels of blood pressure.
Government takes first step towards regulating GPs with a specialist interest
Authors: Julia Schofield
Journal: BMJ (2007)

The Department of Health has launched new commissioning guidance for primary care trusts aimed at setting standards for high quality care wherever services are delivered.

Members of the public who took part in the consultation leading to the 2006 white paper Our Health, Our Care, Our Say made it clear that although they thought that receiving medical care closer to home was a good idea, this must not be at the expense of quality. 

The health …
A CASE OF PERSISTENT INFECTION WITH B. DYSENTERIAE (FLEXNER)
Authors: N. PAUL HUDSON
Journal: JAMA (1922)

A person who harbors pathogenic bacteria but who manifests no indication of infection is known as a healthy or true carrier. The best examples of such persons are seen among those who harbor intestinal pathogens. If, however, the person occasionally presents recurrent symptoms, he might not be considered a true carrier but rather as presenting a chronic case with intermittent manifestations of the disease. A definite distinction cannot be made between the two conditions. A review of the current literature of the last twenty-five years discloses a relatively small number of accurately diagnosed instances of either true carriers or of persons having chronic cases of dysentery. Those persons who harbor the Flexner type of dysentery bacillus are usually more common; their condition is less persistent, and the bacillus is discharged less regularly than in carriers of the Shiga type. 1   Both the true carrier and the person presenting the chronic
Fetal Protection and Employment Discrimination — The Johnson Controls Case
Authors: George J. Annas
Journal: New England Journal of Medicine (1991)

Employers have historically limited women's access to traditionally male, high-paying jobs.1 In one famous case early in this century, the U.S. Supreme Court upheld an Oregon law that forbade hiring women for jobs that required more than 10 hours of work a day in factories. The Chief Justice explained that this restriction was reasonable because "healthy mothers are essential to vigorous offspring" and preserving the physical well-being of women helps "preserve the strength and vigor of the race."2 This rationale was never particularly persuasive, and women's hours have not been limited in traditionally female, low-paid fields of employment, such as . . .
Ph.D. Training in Cancer Biology
Authors: Frank M. Torti, Dario Altieri, James Broach, Hung Fan, Michael Lotze, James Manfredi, Lynn Matrisian, Dihua Yu, Amato Giaccia
Journal: Cancer Research (2008)

Cancer is one of the major afflictions of mankind. In recent years, knowledge about the origins, growth, tissue interactions, and spread of cancer has burgeoned. Descriptive knowledge has been replaced by mechanistic understanding of cancer behavior at the molecular, cellular, and organismal levels
A patient with fever, haemoptysis, and tenderness of calf muscles
Authors: L-W. Ding, P-H. Kuo, P-C. Yang
Journal: European Respiratory Journal (2001)

Case historyA 27-yr-old male presented to the author9s emergency room on August 22, 2000, with a 5-day history of fever, chills, and tenderness of bilateral calf muscles.He also complained of diarrhoea, cough and mild haemoptysis.The patient had a part-time job at a Chinese dessert company during summer vacations.He had been in good health previously.There was no history of blood transfusion, hepatitis, chronic liver disease, drug abuse, alcoholism or recent travel to other countries.On examination, his consciousness was clear.Body temperature was 38.8uC, blood pressure 130/90 mmHg, pulse rate 110 beats?min -1 , and respiratory rate 22 breaths?min - .The sclerae were icteric.The pupils were isocoric with prompt light reflex.The neck was supple, without jugular vein distension or lymphadenopathy.The chest expanded symmetrically and the breathing sounds were clear.There were no heart murmurs.The abdomen was soft and flat, without tenderness or rigidity.The liver and spleen were not palpable.The bowel sounds were active.Tenderness over bilateral calf muscles was noted.There were no skin rashes, petechiae, or ecchymosis.Laboratory studies revealed: a white blood cell (WBC) count of 11.1610 9 cells?L -1 , with 90.5% neutrophil, 5.3% monocytes, and 3.5% lymphocytes; a red blood cell (RBC) count of 4.01610 12 cells?L -1 ; haemoglobin 117 g?L -1 ; and 27610 9 platelets?L -1 .The prothrombin time and activated partial thromboplastin time were within normal limits.The asparate aminotransferase was 183 U?L -1 ; the creatine kinase 3,671 U?L -1 ; total bilirubin 5.8 mg?L -1 ; blood urea nitrogen 150 mg?L -1 ; and creatinine 14 mg?L -1 .The smears of peripheral blood were negative for parasites
All-Terrain Vehicle Injuries: By Accident or by Design
Authors: Janine Jagger
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The data presented on all-terrain vehicle (ATV) injuries in California by Drs Trager and Grayman<sup>1</sup>in the April 25 issue were compelling. In Virginia, a Task Force on Head Injury has recently completed its work, part of which included an assessment of the role of ATVs as a cause of brain trauma. Reports were obtained from the Virginia Department of Motor Vehicles Crash Investigation Team, who evaluated the conditions under which ATV-related deaths and serious injuries occurred. Their reports showed that one or more of the following factors were present in the ATV crashes studied between Sept 1, 1983, and May 31, 1985: high speed (&gt;25 mph), low operator age (the youngest injured operator was 5 years old), public road use, three-wheel ATV design, and no protective clothing. In fatal crashes, massive brain or spinal cord injuries were present. In light of the available information, the task
Lung volumes, ventilatory capacity, and transfer factor in healthy British boy and girl twins
Authors: J. E. Cotes, J. M. Dabbs, A. M. Hall, A. T. Axford, K. M. Laurence
Journal: Thorax (1973)

<b>Cotes, J. E., Dabbs, J. M., Hall, A. M., Axford, A. T., and Laurence, K. M. (1973)</b>. <i>Thorax</i>, <b>28</b>, 709-715. <b>Lung volumes, ventilatory capacity, and transfer factor in healthy British boy and girl twins</b>. Normal values are reported for the lung volumes, ventilatory capacity, and transfer factor of 212 healthy British twin children aged 8 to 16 years. The boys and the girls share a common relationship to height for the residual volume, peak expiratory flow rate, and <i>K</i>co (transfer factor per litre of lung volume). For the inspiratory capacity and the transfer factor, also its membrane component (<i>D</i>m), the values for the boys exceed those for the girls by, on average, 10%. This difference may be due, at least in part, to the boys taking more exercise.
Needed: Original First Issue of JAMA
Authors: Arthur W. Hafner
Journal: JAMA (1984)

<h3>To the Editor.—</h3> When the staff of<i>JAMA</i>began their centennial research, the library staff was asked to find a volume 1, No. 1 issue of<i>JAMA</i>published July 14, 1883, with a reproducible cover and full complement of advertising pages. Our own archives had only copies bound in a fashion that eliminated the covers and advertisements. After diligent searching through university collections we learned that this was a universal practice. Each premiere<i>JAMA</i>we tracked down had the covers and ads missing. The only unbound copy to be found was at the National Library of Medicine. They were gracious enough to let us photograph the cover and advertising pages<i>JAMA</i>needed to complete the fine reproduction published July 8, 1983. The library is now seeking its own copy of an intact<i>JAMA</i>from July 14, 1883. We are hoping that a private collector or one of the membership might
Possible Genetic Consequences of Family Planning
Authors: Ei Matsunaga
Journal: JAMA (1966)

Family planning means to have children in a desired number, each child at a desired time. Although the parental desire in this regard may be different in individual families, a more or less uniform pattern of reproduction would emerge from practicing family planning, since this need is conditioned by life circumstances that are rather common to all members of the society. Thus, if an appreciable fraction of a population practices it, a change in demographic trends, namely, decline in variances would be expected not only in the number of children per family but also in birth order and parental ages in live-birth data. As family planning is usually used to limit family size, a second sign would be decline in the mean number of children and the mean birth order, while the mean of the parental ages may scarcely be affected. The purpose of this paper is to review the
Abstract P3-14-15: Nabrax: Neoadjuvant therapy of breast cancer with weekly nab-paclitaxel: Final safety of GEICAM 2011-02
Authors: M Martin, S Antolin, A Anton, A Plazaola, E Garcia-Martinez, MA Segui, P Sanchez-Rovira, C Esteban, E Garcia-Valdes, L Calvo, M Quindos, E Carrasco, C Rodriguez-Martin, JI Chacon
Journal: Cancer Research (2013)

Abstract Aims: nab-paclitaxel is an innovative chemotherapy that consists of nano-particles of human serum albumin bound paclitaxel. It exploits the role of albumin as the natural carrier of hydrophobic molecules in human to increase paclitaxel delivery to tumor cells. Weekly nab-paclitaxel showed a superior efficacy compared to every 3-weeks docetaxel in a randomized phase II study in metastatic breast cancer (Gradishar JCO 2009, Clin. Breast Cancer 2012). This single arm phase II trial has been designed to evaluate the activity and safety of weekly nab-paclitaxel as neoadjuvant treatment of early stage breast cancer patients with positive estrogen receptors and negative HER2. Methods: Stage II-III patients were included and treated with nab-paclitaxel weekly at a dose of 150 mg/m2 on days 1, 8 and 15 every 4 weeks for 4 cycles. Following chemotherapy, patients undergo surgery and adjuvant therapy (with radiation, chemo and endocrine therapy) under the investigator criteria. The primary objective is to determine the residual cancer burden class III as measured by the Symmans criteria (JCO 25:4422,2007). Secondary objectives include pathological complete response, overall response, invasive disease free survival, safety and potential correlative biomarkers. Results: Eighty-three patients have been recruited in the study in 13 Spanish institutions. Here we report safety data from 77 patients. Median age was 48 years, 62% were postmenopausal and 94% had ECOG PS 0; most patients were stage II (23% IIa and 36% IIb). A total of 259 cycles have been administered to date; 47 patients completed 4 cycles as planned, 5 patients discontinued treatment early (due to grade 2-3 sensory neuropathy in 4 patients), the remaining patients are still under treatment. The treatment was delayed in 8.1% of patients; nab-paclitaxel doses were omitted and reduced in 3.9% and 9.7% of cycles respectively, for a relative dose intensity of nab-paclitaxel of 97.3%. The most frequent reasons for dose modifications were neutropenia (5.4%) and neuropathy (2.7%). The main grade 2/3 adverse events are described in table 1. Table 1Related adverse events.Per patient (N = 74)Per Cycle (N = 259)NCI-CTCAE vs 4.0. (&amp;gt;5% grade 2-4)Grade 2, N (%)Grade 3, N (%)Grade 2, N (%)Grade 3, N (%)Leukopenia6 (8.1)1 (1.4)11 (4.2)1 (0.4)Neutropenia17(23)7 (9.5)30 (11.6)9 (3.5)Alopecia47(63.5)—121 (46.7)—Fatigue11 (14.9)2 (2.7)17 (6.6)2 (0.8)Neuropathy: Sensory17 (23)2 (2.7)25(9.6)5 (1.9)Musculoskeletal Pain11 (14.9)0 (0)13 (5.0)0 (0) Conclusions: Neoadjuvant therapy with weekly nab-paclitaxel at dose of 150 mg/m2 on days 1, 8 and 15 every 4 weeks was well tolerated. Final safety data for the entire treated patients will be mature and presented at the meeting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-15.
Levels of platinum, palladium, and lead in populations of Southern California.
Authors: D E Johnson, J B Tillery, R J Prevost
Journal: Environmental Health Perspectives (1975)

Results of an epidemiology study of populations living near a freeway and in the high desert area of Southern California for levels of platinum, palladium and lead are presented. Three age groups (children, young adults, and mature adults) were sampled twice for blood, urine, hair, and feces. Air, water, and soil samples were collected in the areas of the residences of the two populations. The primary objective of this study was to obtain baseline levels of these metals prior to the introduction of the catalytic muffler. The samples were collected in September 1974.
Genetic Mutations Associated with Cigarette Smoking in Pancreatic Cancer
Authors: Amanda Blackford, Giovanni Parmigiani, Thomas W. Kensler, Christopher Wolfgang, Siân Jones, Xiaosong Zhang, D. Willams Parsons, Jimmy Cheng-Ho Lin, Rebecca J. Leary, James R. Eshleman, Michael Goggins, Elizabeth M. Jaffee, Christine A. Iacobuzio-Donahue, Anirban Maitra, Alison Klein, John L. Cameron, Kelly Olino, Richard Schulick, Jordan Winter, Bert Vogelstein, Victor E. Velculescu, Kenneth W. Kinzler, Ralph H. Hruban
Journal: Cancer Research (2009)

Cigarette smoking doubles the risk of pancreatic cancer, and smoking accounts for 20% to 25% of pancreatic cancers. The recent sequencing of the pancreatic cancer genome provides an unprecedented opportunity to identify mutational patterns associated with smoking. We previously sequenced >750 million bp DNA from 23,219 transcripts in 24 adenocarcinomas of the pancreas (discovery screen). In this previous study, the 39 genes that were mutated more than once in the discovery screen were sequenced in an additional 90 adenocarcinomas of the pancreas (validation screen). Here, we compared the somatic mutations in the cancers obtained from individuals who ever smoked cigarettes (n = 64) to the somatic mutations in the cancers obtained from individuals who never smoked cigarettes (n = 50). When adjusted for age and gender, analyses of the discovery screen revealed significantly more nonsynonymous mutations in the carcinomas obtained from ever smokers (mean, 53.1 mutations per tumor; SD, 27.9) than in the carcinomas obtained from never smokers (mean, 38.5; SD, 11.1; P = 0.04). The difference between smokers and nonsmokers was not driven by mutations in known driver genes in pancreatic cancer (KRAS, TP53, CDKN2A/p16, and SMAD4), but instead was predominantly observed in genes mutated at lower frequency. No differences were observed in mutations in carcinomas from the head versus tail of the gland. Pancreatic carcinomas from cigarette smokers harbor more mutations than do carcinomas from never smokers. The types and patterns of these mutations provide insight into the mechanisms by which cigarette smoking causes pancreatic cancer.
The Prognostic Value of F-18 Fluorodeoxyglucose Bone Marrow Uptake in Patients With Recent Diagnosis of Multiple Myeloma
Authors: Massimo Castellani, Marco Carletto, Luca Baldini, Rossella Calori, Virgilio Longari, Davide Soligo, Luca Dellavedova, Paolo Gerundini
Journal: Clinical Nuclear Medicine (2009)

Purpose: We assessed the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow of patients with multiple myeloma (MM) in comparison with Tc-99m methoxy-isobutyl-isonitrile (MIBI). Methods: The extent and intensity of FDG and MIBI uptake in the bone marrow of 18 patients with a recent diagnosis of MM were assessed by visual score and by calculating the mean SUV (mSUV) for FDG and the femora/thigh ratio (TG/BKG, [Target/Background ratio]) for MIBI images. These parameters were correlated with clinical indexes of disease using hemoglobin and beta-2-microglobulin levels and plasma cell infiltrate (PCI) percentage. The mean values of the visual score, mSUV, and TG/BKG levels were compared in patients deceased after a relatively short follow-up (n = 9; group A) and in patients with a longer survival or were alive at the end of the study (n = 9; group B). Results: Significant correlations of mSUV and TG/BKG values with PCI percentages and beta-2-microglobulin were found (P < 0.05). The extent of FDG and MIBI bone marrow uptake was greater in patients of group A (P < 0.01). Higher values of mSUV (P < 0.01) and TG/BKG (P < 0.05) were also observed in patients of group A. These results were consistent with the differences (not statistically significant) in hemoglobin, albumin, beta-2-microglobulin levels, and PCI percentages observed in the 2 groups. Conclusion: Our study demonstrates that an increase of FDG bone marrow uptake may predict a more aggressive disease, as much as MIBI uptake. Therefore, an additional analysis of FDG bone marrow images should be performed in patients undergoing PET studies during the initial staging of MM.