tbuckley/cabot-search huggingface dataset:
170. Transfected Cell Arrays for Assessment of Estrogen Receptor Activation in Breast Cancer Cells
Authors: Angela K. Pannier, Zain Bengali, Eric A. Ariazi, V. Craig Jordan, Lonnie D. Shea
Journal: Molecular Therapy (2006)

Transfected cell arrays represent a high-throughput approach to correlate gene expression with functional cell responses, based on gene delivery from a substrate that supports cell adhesion. These arrays provide the ability to express, in parallel, thousands of exogenous genes in live cells, giving real-time information on cellular physiology and gene function. While there have been advances in transfected cell arrays, improvements are needed to this technology, including increasing the cells types that can be efficiently transfected and developing better quantification and normalization methods. We have created an array using soft lithography techniques to pattern DNA-lipid complex deposition. Specifically, a mold was fabricated by curing polydimethylsiloxane (PDMS) into thin, flat disks. Rods of precise diameters were then used to punch holes into the mold, with diameters ranging from 1 mm to 3 mm. The PDMS mold was oxidized and then reversibly sealed to polystyrene slides. The holes in the mold, termed microwells, served as reservoirs for complex deposition onto the polystyrene slides. After deposition, the PDMS mold was peeled away from the polystyrene slide, which was then rinsed thoroughly. DNA complexes were immobilized on the slide in distinct regions, replicating the pattern of microwells in the PDMS mold. Transfection of cells seeded onto these slides was also confined to the patterns. The array was then used to deliver and express DNA sequences that report on the activity of the estrogen receptor (ER) pathway in ER-positive, estrogen-responsive human breast cancer cells. Estrogen receptor α (ERα) expression is the most important biomarker for determining treatment course for clinical breast cancer. Estrogens, via ERα, act as potent mitogens of ER-positive breast cancer. To assess ERα activity, arrays were formed with DNA complexes containing an estrogen-responsive reporter plasmid, pERE(3x)TK- Luc, which contains three repeats of the estrogen response element (ERE) sequence upstream of a minimal thymidine kinase (TK) promoter. This regulated promoter directs firefly luciferase expression in response to transcriptional activation by estradiol (E2)-bound ERα, followed by recruitment of cofactor complexes and basal transcriptional machinery. To normalize for transfection efficiency, DNA complexes also included the pTK-RenLuc plasmid, which contains the same TK promoter driving Renilla luciferase expression. ER-positive MCF-7 breast cancer cells were seeded onto the immobilized DNA-lipid complexes and treated with combinations of E2, the complete antiestrogen fulvestrant or vehicle controls. Firefly and Renilla luciferase expression were analyzed using real-time luciferase imaging, accomplished by adding both luciferase substrates into the media above the cells. Luciferase imaging allowed rapid and quantitative imaging of two luciferase reporter genes in the same cell, which enabled normalization of ER activity.
US medical students in Cuba may be forced to leave
Authors: Jeanne Lenzer
Journal: BMJ (2004)

Eighty underprivileged US medical students studying at Cuba's Latin American School of Medical Sciences may not be able to finish their courses because of a new ruling by President Bush.

As part of Bush's plan to “hasten Cuba's transition” to a “post-Castro, democratic existence” US citizens will no longer be allowed to enjoy “fully hosted” stays in Cuba—in other words, where the Cuban government funds their living and tuition costs.

Molly Millerwise, spokeswoman for the US Treasury Department, said that the ruling is part of “another round of crackdowns of Cuba related sanctions.”

The students, recruited from …
Viral hepatitis. New light on an old disease
Authors: S. Krugman
Journal: JAMA (1970)

Tests for the presence of Australia or hepatitisassociated antigen (HAA) and antibody (anti-HAA) were performed on more than 25,000 serum specimens from more than 700 patients with viral hepatitis. Hepatitisassociated antigen was consistently present in sera from patients with MS-2 strain of serum hepatitis (SH); it was not present in MS-1, infectious hepatitis (IH). Hepatitis-associated antigen was detected earlier after a parenteral exposure to SH than after an oral exposure. Antigen appeared two weeks to two months before onset of jaundice; it was transient in 65% of patients, but persisted for four months to 13 years in 35% of children. The average incubation period of IH (MS-1) was essentially the same following an oral or parenteral exposure (32 to 33 days); in SH (MS-2) it was 65 days after parenteral exposure and 98 days after oral exposure. Gamma-globulin consistently neutralized the infectivity of IH (MS-1) serum; in most cases it did not neutralize the infectivity of SH (MS-2) serum.
Predictors of pretransplant dropout and posttransplant recurrence in patients with perihilar cholangiocarcinoma
Authors: Sarwa Darwish Murad, Ray W. Kim, Terry Therneau, Gregory J. Gores, Charles B. Rosen, James A. Martenson, Steven R. Alberts, Julie K. Heimbach
Journal: Hepatology (2012)

We have previously reported excellent outcomes with liver transplantation for selected patients with early-stage perihilar cholangiocarcinoma (CCA) following neoadjuvant chemoradiotherapy. Our aim was to identify predictors of dropout before transplantation and predictors of cancer recurrence after transplantation. We reviewed all patients with unresectable perihilar CCA treated with neoadjuvant chemoradiation in anticipation for transplantation between 1993 and 2010. Predictors were identified by univariate and multivariate Cox regression analysis of clinical variables. In total, 199 patients were enrolled, of whom 62 dropped out and 131 underwent transplantation at our institution, with six undergoing transplantation elsewhere. Predictors of dropout were carbohydrate antigen 19–9 (CA 19–9) ≥ 500 U/mL (hazard ratio [HR] 2.3; P = 0.04), mass ≥ 3 cm (HR 2.1; P = 0.05), malignant brushing or biopsy (HR 3.6; P = 0.001), and Model for End-Stage Liver Disease (MELD) score ≥ 20 (HR 3.5; P = 0.02). Posttransplant, recurrence-free 5-year survival was 68%. Predictors of recurrence were elevated CA 19–9 (HR 1.8; P = 0.01), portal vein encasement (HR 3.3; P = 0.007), and residual tumor on explant (HR 9.8; P &lt; 0.001). Primary sclerosing cholangitis (PSC), age, history of cholecystectomy, and waiting time were not independent predictors. Conclusion : Outcome following neoadjuvant chemoradiation and liver transplantation for perihilar CCA is excellent. Risk of dropout is related to patient and tumor characteristics and this can be used to guide patient counseling before enrollment. Recurrence risk is mostly associated with presence of residual cancer on explant. Patients with PSC do not have an independent survival advantage over de novo patients, but present with more favorable tumor characteristics.
The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach
Authors: Jan J. Cornelissen, Alois Gratwohl, Richard F. Schlenk, Jorge Sierra, Martin Bornhäuser, Gunnar Juliusson, Zdenek Råcil, Jacob M. Rowe, Nigel Russell, Mohamad Mohty, Bob Löwenberg, Gerard Socié, Dietger Niederwieser, Gert J. Ossenkoppele
Journal: Nature Reviews Clinical Oncology (2012)
Prevention of Smoking
Authors: E. James Feeley
Journal: JAMA (1979)

<h3>To the Editor.—</h3> In a recent COMMENTARY by Richard V. Ebert, MD (240:2159, 1978), he urges physicians to try to reduce the grim toll of lung cancer, chronic bronchitis, and emphysema by encouraging their smoking patients to abstain from cigarettes. He suggests that this approach may be more productive than trying to induce young people to avoid the cigarette habit, since "lectures and counseling are relatively ineffective." Based on my experience in conducting cancer education programs in public schools, I think this pessimism is unwarranted. We have been dealing principally with preteens and early teenagers, using film presentations followed by small discussion groups conducted by advanced high school science students. These presentations have been well received by the young people, probably because of the straightforward, nonpedantic approach and the participation of the older teenagers. Some of our young students go home and convince their parents to stop the habit, and
Paleopathological Evidence of Rheumatoid Arthritis
Authors: Ronald E. Domen
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The study by Appelboom et al (1981;245:483) on the antiquity of rheumatoid arthritis provides pictorial evidence for this disease in the 17th century, approximately 200 years earlier than is generally acknowledged. However, I think that they are in error concerning the lack of evidence for rheumatoid arthritis before this time. The paleopathological literature provides evidence that rheumatoid arthritis was present before the 17th century.<sup>1</sup>One case is that of an Egyptian mummy from the Fifth Dynasty (2750 to 2625 BC).<sup>1,2</sup>The hands were deformed by joint swellings, ulnar deviation of the fingers, hyperextension at the metacarpophalangeal joints, flexion at the interphalangeal joints, and involvement of the temporomandibular joints. American Indian skeletal material from Dickson Mounds, Ill, has disclosed a case of rheumatoid arthritis in an elderly man from the Mississippian period (700 to 1650 AD).<sup>3</sup>The Indian displayed flexed knees and some erosion of
Deaths of children in house fires
Authors: P. Whidden
Journal: BMJ (1996)

EDITOR,—Ian Roberts's editorial on the deaths of children in house fires omits to mention what is overwhelmingly the most important factor in fatal residential fires—namely, cigarettes.1 “Smokers' materials” are the source of ignition in nearly half of the house fires in Britain that result in a death. Matches are not included in the government's definition of this term, and in fatal residential fires the term essentially refers to cigarettes. Any discussion of deaths among children because of house fires ought therefore to mention …
Statin Use and Hospitalization for Sepsis in Patients With Chronic Kidney Disease
Authors: Rajesh Gupta, Laura C. Plantinga, Nancy E. Fink, Michal L. Melamed, Josef Coresh, Caroline S. Fox, Nathan W. Levin, Neil R. Powe
Journal: JAMA (2007)

Patients with chronic kidney disease are at high risk for sepsis and sepsis-related mortality.To assess whether statin use is associated with a reduction in sepsis events [corrected] in dialysis patients.National prospective cohort study that enrolled 1041 incident dialysis patients at 81 US not-for-profit outpatient dialysis clinics from October 1995 to June 1998, with follow-up to January 2005. Statin use was determined by medical record review. Rates of sepsis events [corrected] between statin users and control patients were compared using multivariate regression models, with adjustment for potential confounders in the overall cohort and in a subcohort in which control patients were matched to statin users according to their likelihood (propensity) to have been prescribed a statin.Sepsis events [corrected] were determined through hospital records from the United States Renal Data System (mean follow-up, 3.4 years).There were 303 sepsis events [corrected] Rates of sepsis events [corrected] were significantly lower in patients receiving statins (crude incidence rate, 41/1000 patient-years) than in those not receiving statins (crude incidence rate, 110/1000 patient-years) (P<.001). With adjustment for demographics and dialysis modality, statin users were substantially less likely to be subsequently hospitalized for sepsis (incidence rate ratio, 0.41; 95% confidence interval [CI], 0.25-0.68). Further adjustment for comorbidities and laboratory values continued to show this protective association (incidence rate ratio, 0.38; 95% CI, 0.21-0.67). In the propensity-matched subcohort, statin use was even more protective (incidence rate ratio, 0.24; 95% CI, 0.11-0.49).Use of statins was strongly and independently associated with a reduction in the risk of sepsis events [corrected] in patients who had chronic kidney disease and were receiving dialysis. Randomized trials of statins in patients with chronic kidney disease should examine the prevention of sepsis as a potentially important benefit.
PLATELET REACTIVITY AFTER CLOPIDOGREL IN JAPANESE PATIENTS WITH CORONARY ARTERY DISEASE UNDERGOING PERCUTANEOUS CORONARY INTERVENTION ACCORDING TO CYP2C19 GENOTYPES
Authors: Yuichiro Toma, Koyu Sakai, Masahiko Noguchi, Koji Sato, Soichiro Enomoto, Masashi Kato, Hiroyoshi Yokoi, Masashi Iwabuchi, Hideyuki Nosaka, Masakiyo Nobuyoshi
Journal: Journal of the American College of Cardiology (2011)
Alcohol and Risk of Breast Cancer
Authors: Steven A. Narod
Journal: JAMA (2011)

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EVALUATION OF PREMOTOR REACTION TIME, SENSATION OF POSITION AND JUMP PERFORMANCE ABILITY FOLLOWING RECONSTRUCTIVE ACL OPERATION
Authors: Lee Hoseong
Journal: British Journal of Sports Medicine (2013)

Background Although surgical reconstruction of the anterior cruciate ligament (ACL) is commonly performed to increase stability of the knee, persistent changes in neuromuscular function has frequently been cited as contributing to disability. 1 2 Objective This study investigated neuromuscular function (premotor reaction time, reproductive angle inaccuracy and jump ability) in a sample of patients 12 to 28 months following reconstructive ACL operation. In addition, the effect of leg dominance on neuromuscular function was analyzed in a sample of subjects without knee injury. Methods Ten healthy woman without knee injury and 10 patients following ACL operation participated in the study after they had been screened for neuromuscular function disorders. Premotor reaction time (PRT) of vastus medialis (VM), vastus lateralis (VL), hamstring medialis (HM), and hamstring lateralis (HL) were recorded by electromyography through the examination sudden knee eversion stress. Sensation of position were evaluated as a reproductive angle inaccuracy (RAI) in the difference between a specified angle (15°, 30°, 45°, 60°, and 75°) and the reproduction angle. Two physical therapists evaluated each subject's performance ability using a talent diagnose system (TDS Jump and TDS Flash Jump). Results The patients showed a significant increase in reaction time of hamstring operated legs (p&lt;.05), systemic reaction time (TDS Flash Jump) (p&lt;.05), and significant decrease in grounding time (TDS Jump) of operated legs (p&lt;.05). For correlation coefficient, no statistically significant changes were found. Conclusions It was confirmed that a multi function of neuromuscular had decreased though one year or more passed after ACL reconstructive operation, therefore, should be provide information that recovers a multi function of neuromuscular in rehabilitation after ACL operation.
OBSERVATIONS ON THE RELATION OF THE VIRUS CAUSING RABBIT PAPILLOMAS TO THE CANCERS DERIVING THEREFROM
Authors: Peyton Rous, John G. Kidd, J. W. Beard
Journal: The Journal of Experimental Medicine (1936)

All the strains of the Shope virus thus far tested which give rise to vigorous, progressively enlarging papillomas in domestic rabbits, function as carcinogenic agents by way of these growths. The more pathogenic the virus as evidenced by the brevity of its incubation period and the vigor of the papillomas produced, the sooner and oftener does cancer occur. The number of virus entities contained in the inoculum notably influences the outcome, cancer appearing most frequently in those confluent, papillomatous masses which have resulted from the greatest concentration of the virus material under test. The papillomas experimentally induced by the ordinary inoculation methods are essentially aggregates of proliferating cell families, each the outcome of some primary cell-virus association. Some of these associations are followed more frequently by cancer than others are in the same animal. Cottontail rabbits, the natural hosts of the virus, are notably resistant to its sustained activity, as compared with domestic rabbits. Though often growing rapidly at first, the papillomas of cottontails soon become relatively inert in most cases, and they usually retrogress, and rarely undergo malignant change. In an instance here reported both a squamous cell carcinoma and a metastasizing sarcoma appeared at the base of some papillomas due to experimental inoculation, which had existed on the ears of a cottontail for nearly 2 years. The meaning of the phenomena is discussed.
THE ANTIBODY RESPONSE IN THE HUMAN BEING AFTER INJECTION WITH NORMAL HORSE SERUM
Authors: Louis Tuft, Susan Griffith Ramsdell
Journal: The Journal of Experimental Medicine (1929)

After the injection of normal horse serum in the human being, serum sickness occurs even more regularly than in cases treated with the various immune sera, but this is not accompanied by the production, to any notable degree, of circulating antibodies of the various types that are regularly to be demonstrated after the administration of immune serum and its resulting serum sickness. Since normal horse serum therefore appears to be weakly antigenic, and immune serum highly antigenic for the human being, one must assume that this difference is the result of some alteration in its antigenic characteristics produced during the course of the immunization or of its preparation for use; or that the specific antibody which is responsible for the phenomenon of serum sickness has not yet been identified; or that this phenomenon is not in any way dependent on the presence of the various known antibodies to normal horse serum.
Human Embryonic Stem Cells Develop Into Multiple Types of Cardiac Myocytes
Authors: Jia-Qiang He, Yue Ma, Youngsook Lee, James A. Thomson, Timothy J. Kamp
Journal: Circulation Research (2003)

Human embryonic stem (hES) cells can differentiate in vitro, forming embryoid bodies (EBs) composed of derivatives of all three embryonic germ layers. Spontaneously contracting outgrowths from these EBs contain cardiomyocytes (CMs); however, the types of human CMs and their functional properties are unknown. This study characterizes the contractions and action potentials (APs) from beating EB outgrowths cultured for 40 to 95 days. Spontaneous and electrical field-stimulated contractions were measured with video edge-detection microscopy. β-Adrenergic stimulation with 1.0 μmol/L isoproterenol resulted in a significant increase in contraction magnitude. Intracellular electrical recordings using sharp KCl microelectrodes in beating EB outgrowths revealed three distinct classes of APs: nodal-like, embryonic atrial-like, and embryonic ventricular-like. The APs were described as embryonic based on the relatively depolarized resting membrane potential and slow AP upstroke. Repeated impalements of an individual beating outgrowth revealed a reproducible AP morphology recorded from different cells, suggesting that each outgrowth is composed of a predominant cell type. Complex functional properties typical of cardiac muscle were observed in the hES cell-derived CMs including rate adaptation of AP duration and provoked early and delayed afterdepolarizations. Repolarization of the AP showed a significant role for I Kr based on E-4031 induced prolongation of AP duration as anticipated for human CMs. In conclusion, hES cells can differentiate into multiple types of CMs displaying functional properties characteristic of embryonic human cardiac muscle. Thus, hES provide a renewable source of distinct types of human cardiac myocytes for basic research, pharmacological testing, and potentially therapeutic applications.
Diabetes Insipidus Associated with Wegener's Granulomatosis Successfully Treated with Cyclophosphamide
Authors: Barton F. Haynes, Anthony S. Fauci
Journal: New England Journal of Medicine (1978)

WEGENER'S granulomatosis, a necrotizing granulomatous vasculitis that involves the paranasal sinuses, lungs and glomeruli, rarely involves the brain parenchyma.1 Central-nervous-system involvement is nearly always manifested by cerebral-artery vasculitis, cranial-nerve palsy or opticnerve dysfunction.2 , 3 Before the use of cytotoxic therapy for the disorder, three cases of diabetes insipidus associated with Wegener's granulomatosis were reported.4 5 6 The present report describes a patient with the disorder who had diabetes insipidus and hyperprolactinemia and who was successfully treated with cyclophosphamide.Case ReportIn June, 1974, a 25-year-old man noted the gradual onset of polyuria and polydipsia, with daily urine output of 12 liters. In March, . . .
Doctors and managers.
Authors: A. Seaton
Journal: BMJ (1992)

Charlton and Cuninghame propose regular standard quality checks on computer health records, but this should be cost effective.We fear that the authors underestimate the effort and resources required in manual checking.3In the future, electronic reconciliation of data on patients held on different computers must be pursued.6In the meantime, we suggest that regular feedback of data to general practitioners is likely to improve accuracy and to encourage a higher rate of immunisation in the target populationthe prime objective.Finally, we agree that computers, like humans, should be immunised against attack by viruses.7
Epidemiology of Primary Tuberculosis in an Industrial School
Authors: Joseph H. Bates, William E. Potts, Margaret Lewis
Journal: New England Journal of Medicine (1965)

FOR many years it was generally accepted that primary tuberculosis developed almost exclusively among persons who had prolonged and intimate contact with infectious sources. The mechanism of infection was poorly understood, but it was believed that the organisms spread through the air in particles, the inhalation of which resulted in the development of a pulmonary lesion. Little was known about the precise nature of this process until Wells, Ratcliffe and Crumb1 demonstrated that the size of the inhaled particle was important. Rabbits inhaling 2 or 3 bovine tubercle bacilli dispersed as single units contracted more pulmonary tuberculosis than when inhaling . . .
ACID AND PEPSIN RESPONSE TO GASTRIN I, PENTAGASTRIN, TETRAGASTRIN, HISTAMINE, AND PENTAGASTRIN SNUFF
Authors: K. Jepson, H.L. Duthie, A.N. Fawcett, J.R. Gumpert, D. Johnston, J. Lari, K.G. Wormsley
Journal: The Lancet (1968)