tbuckley/cabot-search huggingface dataset:
Abstract 3360: The hedgehog pathway inhibitor GDC-0449 alters intracellular Ca2+-homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells
Authors: Fei Tian, Rudolf Maria Huber, Kathrin Schrödl, Amanda Tufman, Rosemarie Kiefl, Albrecht Bergner
Journal: Cancer Research (2012)

Abstract Cisplatin-resistance is an important issue in lung cancer. The hedgehog signaling pathway (Hh) has been shown to be activated in cancer. GDC-0449 is a low-molecular Hh pathway inhibitor that binds to and inhibits Hh pathway receptor SMO. It is the first systemic SMO-inhibitor that has entered clinical trials. Recently, we could show that GDC-0449 is effective in lung cancer cell lines and that combination with cisplatin gives an additional effect. However, no data on the effect of GDC-0449 on cisplatin-resistant lung cancer cells are available. We aimed at investigating if the hedgehog pathway inhibitor GDC-0449 is effective in cisplatin-resistant cells and if it alters the intracellular Ca2+-homeostasis. The cytoplasmatic ([Ca2+]cyto) and endoplasmatic ([Ca2+]ER) Ca2+-concentration of HCC (adeno carcinoma of the lung) and H1339 (small cell lung carcinoma) cells was measured with the calcium indicator dye Fura-2 AM. The expression of the inositol-1,4,5-trisphosphate receptor (IP3R) and Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) were analyzed using Western Blot analysis. GDC-0449 inhibited cell growth in cisplatin-naïve and -resistant cells. In both cell types, GDC-0449 increased [Ca2+]cyto and reduced endoplasmatic [Ca2+]ER. Cisplatin failed to considerably alter the Ca2+-homeostasis in resistant cells. The effects of GDC-0449 on the intracellular Ca2+-homeostasis were not mediated by an altered expression of IP3R or SERCA. We demonstrate that GDC-0449 alters the intracellular Ca2+-homeostasis and inhibits cell growth in cisplatin-resistant lung cancer cells. 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 3360. doi:1538-7445.AM2012-3360
Efficacy and Safety of Apixaban in Patients After Cardioversion for Atrial Fibrillation
Authors: Greg Flaker, Renato D. Lopes, Sana M. Al-Khatib, Antonio G. Hermosillo, Stefan H. Hohnloser, Brian Tinga, Jun Zhu, Puneet Mohan, David Garcia, Jozef Bartunek, Dragos Vinereanu, Steen Husted, Veli Pekka Harjola, Marten Rosenqvist, John H. Alexander, Christopher B. Granger
Journal: Journal of the American College of Cardiology (2013)
Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report
Authors: Joshua A. Boyce, Amal Assa'ad, A. Wesley Burks, Stacie M. Jones, Hugh A. Sampson, Robert A. Wood, Marshall Plaut, Susan F. Cooper, Matthew J. Fenton, S. Hasan Arshad, Sami L. Bahna, Lisa A. Beck, Carol Byrd-Bredbenner, Carlos A. Camargo, Lawrence Eichenfield, Glenn T. Furuta, Jon M. Hanifin, Carol Jones, Monica Kraft, Bruce D. Levy, Phil Lieberman, Stefano Luccioli, Kathleen M. McCall, Lynda C. Schneider, Ronald A. Simon, F. Estelle R. Simons, Stephen J. Teach, Barbara P. Yawn, Julie M. Schwaninger
Journal: Journal of Allergy and Clinical Immunology (2010)
TREATMENT OF TUBERCULOSIS BY THE SPAHLINGER METHOD
Authors: L. Williams
Journal: BMJ (1923)

XZIA ORA good use.It should mean more frequent examination of contacts and of home conditions.It should lead to demo, graphv, marking the black spots where tuberculosis was most rife in houses and in industries.It should lead to a proper disinfection, and for this the most important measures were soap and water, fresh air and sunshine.
Fatty Acid Transport and Incorporation into Human Erythrocytes In Vitro*
Authors: Richard K. Donabedian, Arthur Karmen
Journal: Journal of Clinical Investigation (1967)

When human erythrocytes were incubated in vitro with (14)C-labeled free fatty acids bound to serum albumin, labeled fatty acids were incorporated into erythrocyte triglycerides and phospholipids. The first step in this reaction was the transfer of free fatty acids from the albumin to the cells. This transfer was rapid and reversible. The acids were distributed between albumin and cells according to the relative quantities of albumin and cells present. Each acid had a different distribution coefficient. At equilibrium, relatively larger fractions of the stearic and palmitic acids and smaller fractions of the oleic and linoleic were associated with the cells. All these fatty acids were then slowly incorporated into phospholipids and triglycerides. The rate of incorporation of each was a function of its concentration in the cells, but larger fractions of the oleic and linoleic were incorporated than of the stearic, palmitic, myristic, or lauric. The two processes of transfer and incorporation thus had almost opposite selectivities for the different fatty acids. As a result, the fatty acids incorporated into triglycerides and phospholipids resembled in composition the fatty acids on the albumin except for moderately less stearic acid.
A Case of Palpable Parathyroid Tumour
Authors: W. D. Park, P. G. Swann
Journal: BMJ (1952)

On the evidence available it seems that neither arterial nor venous spasm is responsible (Haimovici and Suffness, 1948; De Bakey and Ochsner, 1949).In most of the reported cases factors well known to predispose to venous thrombosis, such as polycythaemia vera, dehydration, cardiac failure, and prolonged recumbency, have been absent.It is well known that phlegmasia alba dolens occurs com- monly during the puerperium, and this also applies to the severe variety of thrombosis which leads to gangrene.Cases of phlegmasia cerulea dolens, however, do not seem to be specially associated with the puerperium, and none of the reported cases have occurred during that period.Treatment This can conveniently be considered from the aspect of the peripheral circulatory failure, of the thrombosis, and of the swollen limb.As regards the peripheral circulatory failure, it is important to recognize that this demands urgent treatment with intravenous fluids which remain within the cardiovascular system.Compatible blood, small pool plasma, or dextran may be used, the amount necessary depending on the degree of the collapse.Treatment of the thrombosis demands the usual combination of heparin and ethyl biscoumacetate, and anticoagulant therapy should be continued until the patient is ambulant.As neither venous nor arterial spasm seems to play an important part, sympathetic blocks, papaverine injections, etc., can reason- ably be omitted.Treatment of the swollen limb entails its elevation above the heart level until the swelling has subsided, followed by external support to the limb in the form of an elastic stock- ing or of crepe bandages when the patient becomes ambu- lant.Persistent swelling of the limb despite these measures is no different from that following phlegmasia alba dolens, and the treatment of this is beyond the scope of this paper.Summay A case of phlegmasia cerulea dolens is described.Points of interest from the literature are discussed.Active treatment of the phase of collapse and peripheral circulatory failure is advocated.At the same time full doses of anticoagulants should be given.The further course is not dissimilar from that of the better-known phlegmasia alba dolens.
Avoiding interpretive pitfalls when assessing arrhythmia suppression after myocardial infarction: Insights from the long-term observations of the placebo-treated patients in the Cardiac Arrhythmia Pilot Study (CAPS)
Authors: Craig M. Pratt, Al Hallstrom, Pierre Theroux, Donald Romhilt, James Coromilas, James Myles
Journal: Journal of the American College of Cardiology (1991)
Canadian trainees could be accused of "battery" for performing pelvic examinations under anaesthesia, say legal analysts
Authors: B. Kermode-Scott
Journal: BMJ (2012)

Recently updated Canadian guidelines concerning patient consent for pelvic examinations undertaken during anaesthesia contain a “major flaw” because they do not specifically mention trainees, say health law experts.

In 2010, the Society of Obstetricians and Gynaecologists of Canada (SOGC) and the Association of Academic Professionals in Obstetrics and Gynaecology of Canada (APOG) released an updated policy statement regarding pelvic examinations performed on women under anaesthesia. Unlike the previous 2006 guideline that applied to “medical trainees” (explicitly including students and residents), the updated statement for the most part applies only to “medical …
Low-dose UVA1 phototherapy in systemic sclerosis: effects on acrosclerosis
Authors: Alexander Kreuter, Frank Breuckmann, Andrea Uhle, Norbert Brockmeyer, Gregor von Kobyletzki, Marcus Freitag, Markus Stuecker, Klaus Hoffmann, Thilo Gambichler, Peter Altmeyer
Journal: Journal of the American Academy of Dermatology (2004)
Determinants and characteristics of mean corpuscular volume and hemoglobin concentration in white <i>HFE</i> C282Y homozygotes in the hemochromatosis and iron overload screening study
Authors: Christine E. McLaren, James C. Barton, Victor R. Gordeuk, Lu Wu, Paul C. Adams, David M. Reboussin, Mark Speechley, Henry Chang, Ronald T. Acton, Emily L. Harris, Andrea M. Ruggiero, Oswaldo Castro
Journal: American Journal of Hematology (2007)

Abstract Elevated mean corpuscular volume (MCV) is common in persons with hemochromatosis associated with HFE C282Y homozygosity. We evaluated data from the subset of non‐Hispanic white participants in the Hemochromatosis and Iron Overload Screening Study to determine if elevated MCV in C282Y homozygotes is related to this genotype or to serum iron measures. Regression analysis was used to model MCV and Hb from transferrin saturation (TfSat), serum ferritin (SF), mean corpuscular hemoglobin concentration, red blood cell count, age, HFE genotype, Field Center, and presence of liver‐related abnormalities in C282Y homozygotes and control subjects without HFE mutations (wt/wt genotype). Mean MCV was higher in C282Y homozygotes than in HFE wt/wt controls (94.4 vs. 89.7 fL in women; 95.3 vs. 91.2 fL in men; P &lt; 0.0001 for both). These differences were largely associated with increased mean TfSat and SF in C282Y homozygotes. Adjusted mean MCV was 92.0 fL (95% confidence interval, 91.1, 92.9) in female C282Y homozygotes and 90.9 fL (90.3, 91.5) in controls. Among women with SF in the reference range 20–200 μg/L, adjusted mean MCV was 92.9 fL, (91.7, 94.2) in C282Y homozygotes, 1.8 fL higher than in controls ( P = 0.013). The adjusted mean MCV of male C282Y homozygotes and controls was similar ( P = 0.30). Adjusted mean Hb was 0.2 g/dL higher in women with C282Y/C282Y than in controls. Greater mean MCV in C282Y homozygosity reflects increased mean TfSat and mean SF in men and women; an additional effect of genotype on MCV and Hb was detected in women. Am. J. Hematol. 82:898–905, 2007. © 2007 Wiley‐Liss, Inc.
Chimerism and minimal residual disease monitoring after reduced intensity conditioning (RIC) allogeneic transplantation
Authors: JA Pérez-Simón, D Caballero, M Diez-Campelo, R Lopez-Pérez, G Mateos, C Cañizo, L Vazquez, B Vidriales, MV Mateos, M Gonzalez, JF San Miguel
Journal: Leukemia (2002)
The first George W
Authors: W. Moore
Journal: BMJ (2009)

When any politician sneezes or mops a brow, flunkies flap in panic and rivals circle greedily. When that politician is leader of the world’s largest democracy, any hint of less than tip top health commands global attention.

Of America’s 44 presidents so far, eight have died in office, while many have had life threatening episodes, ranging from Franklin D Roosevelt’s paralysing illness (probably polio) to George W Bush’s encounter with a pretzel. But no US president has borne such ill health—nor suffered quite so much at the hands of his doctors—as the first.

Broad shouldered and more than 6 feet (1.8 m) tall, George Washington (1732-99) battled with no fewer than 10 bouts of …
Relative contribution of contact and complement activation to inflammatory reactions in arthritic joints.
Authors: J.J Abbink, A.M Kamp, J.H Nuijens, A.J Erenberg, A.J Swaak, C.E Hack
Journal: Annals of the Rheumatic Diseases (1992)

Although both the complement and contact system are thought to contribute to the inflammatory reaction in arthritic joints, only activation of complement has so far been well established, whereas contact activation and its contribution to arthritis has not been systematically explored. Complement and contact activation were assessed in 71 patients with inflammatory arthropathies and 11 with osteoarthritis using sensitive assays for C3a, and C1-inhibitor (C1INH)-kallikrein and C1INH-factor XIIa complexes respectively. Increased plasma concentrations of kallikrein-and factor XIIa-C1INH complexes were found in two and seven of the 71 patients with inflammatory arthropathies, respectively, and in none of the patients with osteoarthritis. Increased synovial fluid concentrations of kallikrein and factor XIIa complexes occurred in 13 and 15 patients with inflammatory joint diseases respectively, and in two patients with osteoarthritis. Contact system parameters did not correlate with clinical symptoms, local activity, or neutrophil activation. In contrast, synovial fluid concentrations of C3a and C1INH-C1 complexes were increased in all patients and in 20 patients with inflammatory arthropathies respectively, and were higher in patients with a higher local activity score. Synovial fluid C3a correlated with parameters of neutrophil activation such as lactoferrin. Increased plasma concentrations of C3a and C1INH-C1 complexes occurred in 13 and 11 patients with inflammatory joint diseases, and in one and two patients with osteoarthritis respectively. Plasma concentrations of C3a correlated with the number of painful joints. Thus contact activation occurs only sporadically in patients with arthritis and contributes little if anything to the local inflammatory reaction and neutrophil activation. These latter events are significantly related to the extent of complement activation.
Malpractice — A Break with the Past
Authors: Neil L. Chayet
Journal: New England Journal of Medicine (1968)

THE "locality rule" has for many years been one of the most important facets of the legal standard to which a physician is held when his conduct is to be judged in a court of law. This standard has traditionally been that the physician must act as another prudent physician practicing in the same community would have acted under the same circumstances.Recently, the Supreme Judicial Court of Massachusetts completely rejected the "locality rule" in a landmark decision,† dealing another severe blow to the defense of medical malpractice claims. This decision, along with other recent erosion of the traditional defenses . . .
ANGIOSCOPIC ASSESSMENT OF PERI-STENT CONTRAST STAINING FOLLOWING DRUG-ELUTING STENT IMPLANTATION
Authors: Takayuki Ishihara, Masaki Awata, Fusako Sera, Masashi Fujita, Tetsuya Watanabe, Osamu iida, Shin Okamoto, Tomoharu Dohi, tsuyoshi mishima, Kei Sato, Kiyonori Nanto, Yukika Mizukami, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2012)
gp39-CD40 interactions are essential for germinal center formation and the development of B cell memory.
Authors: T M Foy, J D Laman, J A Ledbetter, A Aruffo, E Claassen, R J Noelle
Journal: The Journal of Experimental Medicine (1994)

gp39, the ligand for CD40 expressed on activated CD4+ T helper cells, is required for the generation of antibody responses to T-dependent (TD) antigens. Treatment of mice with anti-gp39 in vivo inhibits both primary and secondary antibody formation to TD, but not T-independent antigens. However, the role of this receptor-ligand pair in the development of germinal centers and the generation of B cell memory is as yet undefined. Using an antibody to gp39, this study examines the in vivo requirement for gp39-CD40 interactions in the induction of germinal center formation, as well as in the generation of B cell memory. Animals were immunized, treated in vivo with anti-gp39, and evaluated using immunohistochemical staining for the presence of splenic germinal centers 9-11 d after immunization. The results demonstrate that the formation of germinal centers was completely inhibited as a result of treatment with anti-gp39. Moreover, adoptive transfer experiments demonstrate that the generation of antigen-specific memory B cells is also inhibited as a consequence of blocking gp39-CD40 interactions. Taken together, the data demonstrate that gp39-CD40 interactions are critical not only for the generation of antibody responses, but also in the development of B cell memory.
Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis
Authors: Frédéric Pendino, Eric Nguyen, Inge Jonassen, Bjarte Dysvik, Abdulkader Azouz, Michel Lanotte, Evelyne Ségal-Bendirdjian, Johan R. Lillehaug
Journal: Blood (2009)
Echocardiographic characterisation of left ventricular geometry of professional male tennis players
Authors: Ross Q Osborn, Walter C Taylor, Keith Oken, Marcello Luzano, Michael Heckman, Gerald Fletcher
Journal: British Journal of Sports Medicine (2007)

Background: The cardiac characteristics of various types of athletes have been defined by echocardiography. Athletes involved in predominately static exercise, such as bodybuilders, have been found to have more concentric hypertrophy, whereas those involved in dynamic exercise, such as long distance runners, have more eccentric hypertrophy. Tennis at the elite level is a sport that is a combination of static and dynamic exercise. Objective: To characterise left ventricular geometry including left ventricular hypertrophy by echocardiography in male professional tennis players. Design: Retrospective study of screening echocardiograms that were performed on male professional tennis players. Setting: All echocardiograms were performed at the Mayo Clinic (Jacksonville, Florida, USA) between 1998–2000. Participants: A total of 41 male professional tennis players, with a mean age of 23. Results: Left ventricular hypertrophy was present in 30 of 41 subjects (73%, 95% CI: 57%–86%). The majority of players manifested eccentric hypertrophy (n = 22, 54%). Concentric hypertrophy (n = 9, 22%) and normal geometry (n = 7, 17%) were encountered with similar frequency. Only 7% (n = 3) manifested concentric remodelling. The mean thickness of both the interventricular septum and the posterior wall was 11.0 mm. The mean LVEDd was 55 mm. The mean RWT was 0.41. The mean LVMI was 130 gm/m 2 and the mean EF was 64%. Five of the 41 subjects had an abnormal septal thickness of 13 mm. Conclusion: This was the first study to specifically describe the full range of echocardiographically-determined left ventricular geometry in professional male tennis players. The majority of subjects exhibited abnormal geometry, predominantly eccentric hypertrophy.
Relapsing polychondritis: an autoimmune disease?
Authors: R N Clayton, R Hoffenberg
Journal: BMJ (1978)

Measurements of exhaled <sup>37</sup>Ar produced by total-body neutron irradiation of <sup>40</sup>Ca were used to determine total-body calcium in 16 human subjects. There was a good correlation between body calcium using the 30-min postirradiation breath sample of <sup>37</sup>Ar and body calcium determined by measurement of <sup>49</sup>Ca.
Socioeconomic status and coronary heart disease risk factor trends. The Minnesota Heart Survey.
Authors: R V Luepker, W D Rosamond, R Murphy, J M Sprafka, A R Folsom, P G McGovern, H Blackburn
Journal: Circulation (1993)

BACKGROUND Socioeconomic status (SES) indicators including education, income, and occupation are associated with coronary heart disease (CHD) risk factors, morbidity, and mortality. In most industrialized nations, individuals with less education, lower income, and blue collar occupations have the highest CHD rates. It is suggested by some that these differences by SES are increasing even as age-adjusted CHD mortality declines. METHODS AND RESULTS The Minnesota Heart Survey includes measurement of CHD risk factors and behaviors in population-based samples of Minneapolis-St. Paul adults aged 25 to 74 years in 1980 to 1982 (N = 3243) and 1985 to 1987 (N = 4538). Education was significantly and inversely related to blood pressure, cigarette smoking, body mass index, and a summary risk score for both men and women. Serum cholesterol was inversely related to education in women but not in men. Education was positively associated with leisure physical activity and health knowledge. Associations with household income were less consistent in magnitude and direction. Risk characteristics improved significantly between the 1980 to 1982 and 1985 to 1987 surveys. These changes were similar across education and household income levels. CONCLUSIONS Improvement in CHD risk factors over time unrelated to education or income suggests that population-wide factors such as improved health knowledge, availability of healthy food items, hypertension treatment, and restrictions on cigarette smoking are operating beneficially in all SES groups. Although the SES gradient in risk factors is not increasing, it remains substantial and indicates directions for future prevention efforts.
Adult T‐cell leukemia developing during immunosuppressive treatment in a renal transplant recipient
Authors: Hisashi Tsurumi, Kenzaburo Tani, Toshihisa Tsuruta, Risa Shirato, Tadahiro Matsudaira, Arinobu Tojo, Chikashi Wada, Hisanori Uchida, Keiya Ozawa, Shigetaka Asano
Journal: American Journal of Hematology (1992)

Abstract We report a case of a 32‐year‐old male, an asymptomatic carrier of human T‐cell leukemia virus type 1 (HTLV‐1), who underwent a renal transplantation and developed adult T‐cell leukemia (ATL) during the course of posttransplant immunosuppressive treatment. He was treated with combination chemotherapies consisting of cyclophosphamide, vincristine, doxorubicin, prednisolone, cisplatin, cytosine arabinoside, etoposide, and methyl‐prednisolone, without any improvement. Bestrabucil (KM2210), a conjugate of chlorambucil and estradiol, was administered as an alternative therapy; this therapy successfully suppressed his leukemic cell growth, and partial remission was achieved. Posttransplant immunosuppressive therapy with prednisolone, mizoribine, and cyclosporin A might have been the predominant cause of the transition from an asymptomatic HTLV‐1 infection to overt ATL. A careful approach is required with HTLV‐1 asymptomatic carriers who need organ transplantation followed by immunosuppressive treatment. © 1992 Wiley‐Liss, Inc.