tbuckley/cabot-search huggingface dataset:
A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
Authors: Nathaniel Rothman, Montserrat Garcia-Closas, Nilanjan Chatterjee, Nuria Malats, Xifeng Wu, Jonine D Figueroa, Francisco X Real, David Van Den Berg, Giuseppe Matullo, Dalsu Baris, Michael Thun, Lambertus A Kiemeney, Paolo Vineis, Immaculata De Vivo, Demetrius Albanes, Mark P Purdue, Thorunn Rafnar, Michelle A T Hildebrandt, Anne E Kiltie, Olivier Cussenot, Klaus Golka, Rajiv Kumar, Jack A Taylor, Jose I Mayordomo, Kevin B Jacobs, Manolis Kogevinas, Amy Hutchinson, Zhaoming Wang, Yi-Ping Fu, Ludmila Prokunina-Olsson, Laurie Burdett, Meredith Yeager, William Wheeler, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Alison Johnson, Molly Schwenn, Margaret R Karagas, Alan Schned, Gerald Andriole, Robert Grubb, Amanda Black, Eric J Jacobs, W Ryan Diver, Susan M Gapstur, Stephanie J Weinstein, Jarmo Virtamo, Victoria K Cortessis, Manuela Gago-Dominguez, Malcolm C Pike, Mariana C Stern, Jian-Min Yuan, David J Hunter, Monica McGrath, Colin P Dinney, Bogdan Czerniak, Meng Chen, Hushan Yang, Sita H Vermeulen, Katja K Aben, J Alfred Witjes, Remco R Makkinje, Patrick Sulem, Soren Besenbacher, Kari Stefansson, Elio Riboli, Paul Brennan, Salvatore Panico, Carmen Navarro, Naomi E Allen, H Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Neil Caporaso, Maria Teresa Landi, Federico Canzian, Borje Ljungberg, Anne Tjonneland, Francoise Clavel-Chapelon, David T Bishop, Mark T W Teo, Margaret A Knowles, Simonetta Guarrera, Silvia Polidoro, Fulvio Ricceri, Carlotta Sacerdote, Alessandra Allione, Geraldine Cancel-Tassin, Silvia Selinski, Jan G Hengstler, Holger Dietrich, Tony Fletcher, Peter Rudnai, Eugen Gurzau, Kvetoslava Koppova, Sophia C E Bolick, Ashley Godfrey, Zongli Xu, José I Sanz-Velez, María D García-Prats, Manuel Sanchez, Gabriel Valdivia, Stefano Porru, Simone Benhamou, Robert N Hoover, Joseph F Fraumeni, Debra T Silverman, Stephen J Chanock
Journal: Nature Genetics (2010)
Abstract 3504: Targeting the Akt pathway and HDAC signaling in prostate cancer
Authors: Silvia Paesante, Marie Kiersten Miles, Holly Nguyen, Robert Vessella, Roberto Pili
Journal: Cancer Research (2011)

Abstract Loss of the tumor suppressor phosphatase and tensin homolog protein (PTEN), a negative regulator of the survival Akt pathway, and elevated levels of histone deacetylase (HDAC) enzymes which regulate DNA transcription, correlated positively with the prostate cancer progression, recurrence and metastasis. MK-2206 is an allosteric Akt inhibitor with a broad antitumor activity; clinical studies have recently been completed in patients with solid tumors, showing MK-2206 good tolerability and evidences of clinical activity. vorinostat, an HDAC inhibitor, is involved in more than 100 clinical trials in solid tumors and it showed antitumor activity in different prostate cell lines. In this study we hypothesized that combination of MK-2206 and vorinostat may provide a greater antitumor efficacy, targeting different survival pathways activated in prostate cancer. Different prostate cell lines were tested in both in vitro and in vivo xenograft models. LuCaP23.1. hormone-sensitive tumors were placed subcutaneously into male SCID mice. Tumor growth was assessed twice weekly by using serial caliper measurements. Luciferase-transfected PC3 hormone-independent tumor cells were injected in the right tibiae of male SCID mice and tumor progression was monitored weekly by bioluminescence assay using the Xenogen IVIS Living Imaging System. At the end of the experiment, Faxitron radiographs of the tibiae were taken. Mice were treated with MK-2206 at 120 mg/kg/d by oral gavage and i.p. injection of vorinostat at 100 mg/kg/d, 5 days per week. In vitro treatment of PC3 cells showed that both MK-2206 and vorinostat affected cell proliferation in a dose and time dependent manner, with a greater effect in combination. Western blot experiments validated p-Akt protein level inhibition due to MK-2206 treatment. Preliminary PC3 and LuCaP23.1. xenograft in vivo experiments confirmed the therapeutic activity of MK-2206 and vorinostat as single agents. The combination therapy showed a modest but greater inhibition of tumor growth in the PC3 xenograft bone metastatic model though not statistically significant. The antiproliferative effect of this combination was more evident in the subcutaneously LuCaP 23.1. xenograft model. This study showed for the first time the therapeutic association of MK-2206 and vorinostat in prostate cancer. We expect to further investigate the MK-2206 +/- vorinostat therapy and to provide new insight into the role of HDACs signaling and Akt pathway in prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3504. doi:10.1158/1538-7445.AM2011-3504
Relationships Among Total IgE and Rhinovirus-induced Interferons in Peripheral Blood
Authors: D.J. Montville, A.S. Pratt, V.P. Rajamanickam, N.C. Levinsky, C.J. Tisler, R.E. Gangnon, M.A. Gill, D.J. Jackson
Journal: Journal of Allergy and Clinical Immunology (2011)
Winter mortality in elderly people in Britain: Action on outdoor cold stress is needed to reduce winter mortality
Authors: William R Keatinge, Gavin C Donaldson
Journal: BMJ (2004)

EDITOR—The paper by Wilkinson et al, on people aged over 75, makes a useful addition to the evidence that winter mortality in Britain is now not caused primarily by deprivation and failure to heat homes.1 In addition to other evidence they quote, a recent study on younger people provides positive indications that cold exposure outside the home causes winter mortality regardless …
EARLY IMPROVEMENT OF LEFT ATRIAL FUNCTION AND MORPHOLOGY AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION: A SPECKLE–TRACKING LONGITUDINAL STUDY
Authors: Flavio D'Ascenzi, Alessandro Iadanza, Matteo Cameli, Matteo Lisi, Giuseppe Sinicropi, Rosanna Reccia, Valeria Curci, Sergio Mondillo, Carlo Pierli
Journal: Journal of the American College of Cardiology (2013)
Penetrating atherosclerotic aortic ulcer: documentation by transesophageal echocardiography
Authors: Isidre Vilacosta, José Alberto San Román, Paloma Aragoncillo, Joaquín Ferreirós, Ramiro Mendez, Catherine Graupner, Elena Batlle, Javier Serrano, Angel Pinto, José Manuel Oyonarte
Journal: Journal of the American College of Cardiology (1998)
CLINICAL OBSERVATIONS IN STOMACH SURGERY.
Authors: A. J. OCHSNER
Journal: JAMA (1903)

Surgery of the stomach is still in a developmental state. Many surgeons are making progress in this field, and although there can not as yet be many conclusions which can reasonably be expected to be permanent, still it seems worth the effort to exchange the points of clinical experience at this time. It is, of course, out of the question to discuss this subject thoroughly in the time given to a paper in this Section, but I believe that it will be possible to present the features which seem of greatest practical importance as they have impressed themselves on me in my clinical observations. Ultimately the greatest portion of stomach surgery must be done for the relief of gastric ulcer or one of its various sequelæ—hemorrhage, perforation, adhesions, cicatricial contraction with pyloric obstruction and its consequent gastric dilatation, hour-glass stomach and carcinoma. The wider my field of observation has become
Pathophysiology of chronic tubulo-interstitial disease in rats. Interactions of dietary acid load, ammonia, and complement component C3.
Authors: K A Nath, M K Hostetter, T H Hostetter
Journal: Journal of Clinical Investigation (1985)

The human end-stage kidney and its experimental analogue, the remnant kidney in the rat, exhibit widespread tubulo-interstitial disease. We investigated whether the pathogenesis of such tubulo-interstitial injury is dependent upon adaptive changes in tubular function and, in particular, in ammonia production when renal mass is reduced. Dietary acid load was reduced in 1 3/4-nephrectomized rats by dietary supplementation with sodium bicarbonate (NaHCO3), while control rats, paired for serum creatinine after 1 3/4 nephrectomy, were supplemented with equimolar sodium chloride. After 4-6 wk, NaHCO3-supplemented rats demonstrated less impairment of tubular function as measured by urinary excretory rates for total protein and low molecular weight protein and higher transport maximum for para-aminohippurate per unit glomerular filtration rate, less histologic evidence of tubulo-interstitial damage, less deposition of complement components C3 and C5b-9, and a lower renal vein total ammonia concentration. Such differences in tubular function could not be accounted for simply on the basis of systemic alkalinization, and differences in tubular injury could not be ascribed to differences in glomerular function. Because nitrogen nucleophiles such as ammonia react with C3 to form a convertase for the alternative complement pathway, and because increased tissue levels of ammonia are associated with increased tubulo-interstitial injury, we propose that augmented intrarenal levels of ammonia are injurious because of activation of the alternative complement pathway. Chemotactic and cytolytic complement components are thereby generated, leading to tubulo-interstitial inflammation. Thus, alkali supplementation reduces chronic tubulo-interstitial disease in the remnant kidney of the rat, and we propose that this results, at least in part, from reduction in cortical ammonia and its interaction with the alternative complement pathway.
PDX-1 haploinsufficiency limits the compensatory islet hyperplasia that occurs in response to insulin resistance
Authors: Rohit N. Kulkarni, Ulupi S. Jhala, Jonathon N. Winnay, Stan Krajewski, Marc Montminy, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2004)

Inadequate compensatory β cell hyperplasia in insulin-resistant states triggers the development of overt diabetes. The mechanisms that underlie this crucial adaptive response are not fully defined. Here we show that the compensatory islet-growth response to insulin resistance in 2 models — insulin receptor (IR)/IR substrate–1 (IRS-1) double heterozygous mice and liver-specific IR KO (LIRKO) mice — is severely restricted by PDX-1 heterozygosity. Six-month-old IR/IRS-1 and LIRKO mice both showed up to a 10-fold increase in β cell mass, which involved epithelial-to-mesenchymal transition. In both models, superimposition of PDX-1 haploinsufficiency upon the background of insulin resistance completely abrogated the adaptive islet hyperplastic response, and instead the β cells showed apoptosis resulting in premature death of the mice. This study shows that, in postdevelopmental states of β cell growth, PDX-1 is a critical regulator of β cell replication and is required for the compensatory response to insulin resistance.
Abstract 5522: Increase of Th1/Treg ratio in peripheral blood of breast cancer patients with autologous formalin-fixed tumor vaccine
Authors: Fumito Kuranishi
Journal: Cancer Research (2011)

Abstract Introduction: Autologous formalin-fixed tumor vaccine (AFTV) containing formalin-fixed and/or paraffin-embedded tumor fragments is able to induce tumor specific CTL and suppresses recurrence of hepatocellular carcinoma after resection (Clin Cancer Res 2004; 10: 1574-9). We have used delayed-type hypersensitivity (DTH) test as a parameter of cellular immune response. We also found that slight but consistent population change has occurred in peripheral blood T lymphocytes after AFTV treatment. Method: Thirty two breast cancers were operated in our hospital. AFTV was injected intradermally. DTH response to the tumor fragments without any adjuvant was determined if erythema was 10mm or more. Results: After operation, standard chemotherapy, and enough time have passed to recover immunological function, we examined change of peripheral blood T-cell population in 32 cases with breast cancer. Among them, 27 cases turned DTH response from negative to positive after AFTV injection. In these patients, WBC counts increased 1.11 times; lymphocytes, 1.09 times; Th1 in CD4+ T cells, 1.07 times; regulatory T cells (Treg) in CD4+ T cells, 0.95 times, and Th1/Treg ratio, 1.17 times (statistically significant, 95%CI was 1.060-1.284). Conclusion: AFTV probably strengthen the cellular immune response against cancer by improving Th1/Treg ratio in peripheral blood. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5522. doi:10.1158/1538-7445.AM2011-5522
Liquor Bilirubin Levels and False Prediction of Severity in Rhesus Haemolytic Disease
Authors: B. R. Pridmore, E. G. Robertson, W. Walker
Journal: BMJ (1972)

Liquor bilirubin levels gave a false prediction of outcome for the fetus in 80 out of 716 rhesus-sensitized women referred for treatment during 1965-9. Trauma caused by amniocentesis seemed to be responsible for an increase in the severity of immunization in a significant proportion of cases. In addition, contamination of liquor samples by plasma, particularly fetal plasma, completely invalidated liquor bilirubin estimations. Errors in estimation of gestational length were also found to be associated with misleading results and a poor fetal prognosis.
Familial protein S deficiency is associated with recurrent thrombosis.
Authors: P C Comp, R R Nixon, M R Cooper, C T Esmon
Journal: Journal of Clinical Investigation (1984)

Recent studies have demonstrated that protein C deficiency is associated with recurrent familial thrombosis. In plasma, activated protein C functions as an anticoagulant. This anticoagulant response requires a vitamin K-dependent plasma protein cofactor, referred to as protein S. Since the anticoagulant activity of activated protein C is dependent on protein S, we hypothesized that patients lacking functional protein S might have associated thrombotic disease. Two related individuals with otherwise normal coagulation tests are described whose plasma is not effectively anticoagulated with activated protein C. Addition of purified human protein S to their plasma restores a normal anticoagulant response to activated protein C. We have developed a rapid one-stage clotting assay for protein S to quantitate the level of protein S in their plasma. Plasma is depleted of protein S by immunoadsorption with immobilized antiprotein S antibodies. The resultant plasma responds poorly to activated protein C, but is effectively anticoagulated in a dose-dependent fashion upon addition of purified protein S or small quantities of plasma. The affected individuals possess less than 5% protein S activity. Using Laurell rockets, protein S antigen was detected in the plasma but was at reduced levels of 13 and 18% in the two individuals. When the barium eluate of the patient plasma was chromatographed on quaternary aminoethyl Sephadex, a single peak of protein S antigen devoid of protein S anticoagulant cofactor activity was detected early in the chromatogram. In contrast, the barium eluate from normal donors separated into two peaks, one emerging early and also devoid of anticoagulant cofactor, and the second peak with anticoagulant activity emerging later. The first peak of protein S antigen, from both the normal donor and the patient, chromatographed in the region of the complement component C4-binding protein-protein S complex. These studies suggest that protein S deficiency may result in recurrent thrombotic disease.
Opening my mind:
Authors: C. Malpani
Journal: BMJ (1997)

I was a young consultant gynaecologist in 1975 when I saw a 25 year old woman with large venereal warts. I advised ablating them with cryocautery, but she was not happy with this advice, as she wanted to avoid surgery as far as possible. She went away and when she came back after six weeks I found to my surprise that the warts had disappeared. I asked her if she had had the surgery done elsewhere, but she told me that they had “melted away” after she had taken a homoeopathic …
Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus–encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells
Authors: Joanne R. Flavell, Karl R. N. Baumforth, Victoria H. J. Wood, Gillian L. Davies, Wenbin Wei, Gary M. Reynolds, Susan Morgan, Andrew Boyce, Gemma L. Kelly, Lawrence S. Young, Paul G. Murray
Journal: Blood (2007)
ACUTE OSTEOMYELITIS IN CHILDREN
Authors: C. P. G. Wakeley
Journal: BMJ (1932)

AND THE MAUDSLEY HOSP'ITALS It might be thought that the subject of osteomyelitis in children has become rather hackneyed of late, but there can be no doubt that the disease to-day differs in some respects from that of thirty years ago.In the first place, acute osteomyelitis in children is a disappearing disease, and this is borne out by figures that I have been able to obtain from different hospitals in the United Kingdom.Hospital
Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export
Authors: Peng Lei, Scott Ayton, David I Finkelstein, Loredana Spoerri, Giuseppe D Ciccotosto, David K Wright, Bruce X W Wong, Paul A Adlard, Robert A Cherny, Linh Q Lam, Blaine R Roberts, Irene Volitakis, Gary F Egan, Catriona A McLean, Roberto Cappai, James A Duce, Ashley I Bush
Journal: Nature Medicine (2012)
Doctor Diet, Doctor Quiet and Doctor Merryman.
Authors: None Inquirer.
Journal: JAMA (1894)

Chicago, Nov. 2, 1894. <h3>To the Editor:</h3><h3>Answer:</h3> —The original is as follows: "Si tibi deficiant medici, medici tibi fiant, Hæctria: Mens hilaris. requies, moderata diæta." This was in the famous "<i>Flos Medicinæ</i>" or<i>Regimen Sanitatis Salerni</i>, composed in the year 1099 by Johannes de Mediolanus (John of Milan) with the concurrence of the other professors of the celebrated School of Salernum. This book was first translated in English by Paynell in 1579, and later by Dr. Philemon Holland in 1634. Holland's translation of the sentence reads: " When Physic needs, let these thy doctors bee, Good dyet, quiet thoughts and heart mirthfull free." "Mirth," says Burton, 1621 (Anatomy of Melancholy) "is one of the three Salernitan doctors, Dr. Merryman, Dr. Diet, Dr. Quiet, which
Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor.
Authors: M Lantz, U Gullberg, E Nilsson, I Olsson
Journal: Journal of Clinical Investigation (1990)

Tumor necrosis factor (TNF) is a pleiotropic mediator of inflammatory responses. A cysteine-rich, highly glycosylated 30-kD TNF-binding protein (TNF-BP) purified from urine may have a role in regulation because it protects in vitro against the biological effects of TNF. The cytotoxic effect of TNF on the fibrosarcoma cell line WEHI 164 was inhibited by 50% at a 10-fold excess of TNF-BP. The binding of TNF to the receptor was partially reversed after the addition of TNF-BP. Results from biosynthetic labeling of cells with 35S-cysteine followed by immunoprecipitation with anti-TNF-BP indicated that TNF-BP is formed and released at the cell surface by cleavage because no corresponding cellular polypeptide was observed. A cellular 60-kD polypeptide, which was immunoprecipitated with anti-TNF-BP, may correspond to the transmembrane TNF-receptor molecule and be the precursor of TNF-BP. Thus, TNF-BP appears to be a soluble form of a transmembrane TNF-receptor. Moreover our results demonstrate that the production of TNF-BP is increased when the TNF receptor is downregulated in cells by treatment with TNF or by activation of protein kinase C with phorbol esters. TNF-BP may be an important agent that blocks harmful effects of TNF, and, therefore, useful in clinical applications.
Δ9-Tetrahydrocannabinol in Clinical Oncology
Authors: Don Steven Poster
Journal: JAMA (1981)

After anecdotal reports of marijuana's providing antiemetic activity in cancer chemotherapy patients refractory to standard agents, orally administered Δ9-tetrahydrocannabinol (THC) was formally studied by a number of investigators. In six of seven well-controlled studies, orally administered THC was a superior antiemetic agent compared with control agents. The THC toxic effects are notable but manageable. Patients rarely require hospitalization after the development of THC-induced dysphorias. However, serious toxic effects are uncommon and the most frequently noted effects are somnolence, conjunctivitis, and tachycardias. Because certain subgroups of patients are more prone to have toxicities develop, careful selection of the candidates to receive this agent is mandatory. Overall, the benefits of orally administered THC use represent a major advance in antiemetic therapy. (<i>JAMA</i>1981;245:2047-2051)
IMPACT OF BASELINE SPASM ON 3-YEAR CLINICAL OUTCOME (RECURRENT CHEST PAIN REQUIRING REPEAT CORONARY ANGIOGRAPHY) IN PATIENT WITH POSITIVE CORONARY ARTERY SPASM AS ASSESSED BY ACETYLCHOLINE PROVOCATION TEST
Authors: SangHo Park, Seung-Woon Rha, Taehoon Ahn, Won Yu Kang, Wonyong Shin, Dongkyu Jin, Byoung Geol Choi, Cheol Ung Choi, Chang Gyu Park, Hong-Seog Seo, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2014)
Metabolism of testosterone and androstenedione in normal and ovariectomized women
Authors: G. E. Abraham, J. Lobotsky, C. W. Lloyd
Journal: Journal of Clinical Investigation (1969)

Metabolic clearance rates of testosterone (MCR(T)) and androstenedione (MCR(A)) were determined twice during the same cycle in six normal women, using a constant infusion of testosterone-(3)H and androstenedione-(14)C. Nonlabeled steroids served as internal standards. Plasma concentrations of testosterone (i(T)) and androstenedione (i(A)) were measured, and the blood production of testosterone (P(B) (T)) and of androstenedione (P(B) (A)) were calculated. The interconversions of these two steroids were also estimated. Six ovariectomized women were studied in the same manner. For testosterone, the mean i(T) in the normal women was not significantly different from that in the ovariectomized subjects, whereas the MCR(T) and P(B) (T) were significantly lower in the ovariectomized subjects. For androstenedione, the mean MCR(A) values of the two groups of subjects were not different, whereas the i(A) and P(B) (A) in the normal women were about double those in the ovariectomized subjects. In comparing the follicular and luteal phases of the menstrual cycle in four of six subjects there was no difference in i(T), MCR(T), or P(B) (T), whereas i(A), MCR(A), and P(B) (A) were increased in the luteal phase. In one ovariectomized woman infused with testosterone and androstenedione at physiologic levels, MCR(T) doubled but MCR(A) remained the same. After six wk on estrogen, the same subject did not show any change in MCR(T) after infusion of testosterone. It is suggested that MCR(T) depends on P(B) (T) and on plasma binding of testosterone which is partly estrogen dependent.