tbuckley/cabot-search huggingface dataset:
JAGGED1 Expression Is Associated with Prostate Cancer Metastasis and Recurrence
Authors: Sandro Santagata, Francesca Demichelis, Alberto Riva, Sooryanarayana Varambally, Matthias D. Hofer, Jeffery L. Kutok, Robert Kim, Jeffery Tang, James E. Montie, Arul M. Chinnaiyan, Mark A. Rubin, Jon C. Aster
Journal: Cancer Research (2004)

Abstract Recent studies suggest that NOTCH signaling can promote epithelial-mesenchymal transitions and augment signaling through AKT, an important growth and survival pathway in epithelial cells and prostate cancer in particular. Here we show that JAGGED1, a NOTCH receptor ligand, is significantly more highly expressed in metastatic prostate cancer as compared with localized prostate cancer or benign prostatic tissues, based on immunohistochemical analysis of JAGGED1 expression in human tumor samples from 154 men. Furthermore, high JAGGED1 expression in a subset of clinically localized tumors was significantly associated with recurrence, independent of other clinical parameters. These findings support a model in which dysregulation of JAGGED1 protein levels plays a role in prostate cancer progression and metastasis and suggest that JAGGED1 may be a useful marker in distinguishing indolent and aggressive prostate cancers.
Interpreting spirometry data from South Asian children using the GLI-2012 equations: The SLIC study
Authors: Rachel Bonner, Janet Stocks, Philip Quanjer, Simon Lee, Emma Raywood, Sarah Legg, Dave Sears, Jane Kirkby, Samatha Sonnappa, Sooky Lum
Journal: European Respiratory Journal (2013)

The Global Lung Function Initiative(GLI), recently published the first all-age, multi-ethnic reference equations for spirometry.1 These equations represent huge progress, but specific reference equations for the South-Asian population have yet to be developed. This study aims to derive GLI-2012 coefficients for S.Asian (Indian sub-continent) children in London, UK.

Methods: Anthropometry and spirometry were undertaken in healthy S.Asian children. Coefficients for the “new” ethnic group (S.Asians) were calculated using GLI software (www.lungfunction.org).

Results: Spirometry data from 378 (47% boys) healthy S.Asian children aged 5-11y were available. Compared to White children, FEV1 was lower by a mean (95%CI) of 10% (9%;12%) in S.Asians. A proportional reduction in FVC was observed such that FEV1/FVC was constant between groups. When expressed according to GLI-2012 coefficients for S.Asians, the mean (SD) for FVC, FEV1 and FEV1/FVC z-scores for the S.Asian children approximated 0 (1) suggesting the amended GLI equations are appropriate for use in this population (figure).

![Figure][1] 



Conclusion: GLI-coefficients can be derived for ‘new’ populations, aiding interpretation of spirometry in a multi-ethnic society. Confirmation is needed in larger UK or South Asian based populations spanning the entire age range.

 [1]: pending:yes
Airway inflammation in the elite athlete and type of sport
Authors: J Belda, S Ricart, P Casan, J Giner, J Bellido-Casado, M Torrejon, G Margarit, F Drobnic
Journal: British Journal of Sports Medicine (2007)

Background: The prevalence of asthma and bronchial hyper-responsiveness is greater in elite athletes than in the general population, and its association with mild airway inflammation has recently been reported. Objective: To study the relationship between the type of sport practised at the highest levels of competition (on land or in water) and sputum induction cell counts in a group of healthy people and people with asthma. Material and methods: In total, 50 athletes were enrolled. Medical history, results of methacholine challenge tests and sputum induced by hypertonic saline were analysed Results: Full results were available for 43 athletes, who were classified by asthma diagnosis and type of sport (land or water sports). Nineteen were healthy (10 land and 9 water athletes) and 24 had asthma (13 land and 11 water athletes). Although the eosinophil counts of healthy people and people with asthma were significantly different (mean difference 3.1%, 95% CI 0.4 to 6.2, p = 0.008), analysis of variance showed no effect on eosinophil count for either diagnosis of asthma or type of sport. However, an effect was found for neutrophil counts (analysis of variance: F = 2.87, p = 0.04). There was also a significant correlation between neutrophil counts and both duration of training and bronchial hyper-responsiveness among athletes exposed to water (Spearman’s rank correlations, 0.36 and 0.47, p = 0.04 and 0.04, respectively). Conclusions: Elite athletes who practice water sports have mild neutrophilic inflammation, whether or not asthma is present, related to the degree of bronchial hyper-reactivity and the duration of training in pool water.
Effects of Oral Contraceptive Agents and Sex Steroids on Carbohydrate Metabolism
Authors: R K Kalkhoff
Journal: Annual Review of Medicine (1972)

The article offers a general interpretation of the influence of oral contraceptive agents on glucose tolerance, emphasizing comparisons of synthetic sex hormones. Although there are conflicting reports on steroid-induced diabetes in normal women, their glucose curves are often higher when under oral contraceptive treatment, suggesting that oral contraceptives may induce a form of subclinical diabetes melitus that is reversible. Evidence from diabetic women suggests definite deliterious effects from contraceptive administration. Estradiol, estriol, and estrone may improve glucose tolerance in nondiabetic women and reduce insulin requirements in diabetics. Progesterone has little effect on carbohydrate tolerance, as did synthetic progestin. Conjugated equine estrogens (equilenine or Premarin) may provoke mild to moderate deterioration of carbohydrate tolerance. Parenterally administered natural estrogens and orally administered synthetic derivatives appear to differ sharply in their effects. Sex hormones' effects on carbohydrate metabolism likely involve interactions with insulin and endogenous glucocorticoids.
DNA-dependent protein kinase inhibition blocks asthma in mice and modulates human endothelial and CD4+ T-cell function without causing severe combined immunodeficiency
Authors: Mohamed A. Ghonim, Kusma Pyakurel, Jihang Ju, Paulo C. Rodriguez, Matthew R. Lammi, Christian Davis, Mohammad Q. Abughazleh, Moselhy S. Mansy, Amarjit S. Naura, A. Hamid Boulares
Journal: Journal of Allergy and Clinical Immunology (2014)
726 EARLY HAEMODYNAMIC RESPONSES TO INTERFERON THERAPY IN PATIENTS WITH CHRONIC LIVER DISEASE USING CONTRAST-ENHANCED ULTRASOUND: REGULATION BY HEPATIC STELLATE CELLS?
Authors: J.F. Cobbold, N. Patel, R.D. Goldin, M.E. Crossey, S.H. Morin, J.A. Fitzpatrick, M. Arridge, I.J. Cox, H.C. Thomas, D.O. Cosgrove, M.R. Thursz, E.L. Leen, S.D. Taylor-Robinson
Journal: Journal of Hepatology (2008)
Ten Common Genetic Variants Associated with Colorectal Cancer Risk Are Not Associated with Survival after Diagnosis
Authors: Albert Tenesa, Evropi Theodoratou, Farhat V.N. Din, Susan M. Farrington, Roseanne Cetnarskyj, Rebecca A. Barnetson, Mary E. Porteous, Harry Campbell, Malcolm G. Dunlop
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To date, genomewide association studies have identified 10 genetic loci associated with colorectal cancer (CRC) susceptibility. We hypothesized that these loci might also affect cancer survival. Experimental Design: To determine whether single-nucleotide polymorphisms tagging these 10 loci influenced all-cause and CRC-specific mortality, we prospectively followed survival outcomes for 2,838 Scottish patients recruited soon after a diagnosis of CRC. Survival analysis was conducted using Cox proportional hazard models adjusted for American Joint Committee on Cancer stage, age, and sex. Results: None of the single-nucleotide polymorphisms were found to be statistically significantly associated with all-cause or CRC-specific mortality. Conclusions: We conclude that none of the 10 common genetic variants thus far shown to be associated with CRC risk are associated with survival from CRC. Clin Cancer Res; 16(14); 3754–9. ©2010 AACR.
Identification and Functional Characterization of Human Cd4+Cd25+ T Cells with Regulatory Properties Isolated from Peripheral Blood
Authors: Helmut Jonuleit, Edgar Schmitt, Michael Stassen, Andrea Tuettenberg, Jurgen Knop, Alexander H. Enk
Journal: The Journal of Experimental Medicine (2001)

A subpopulation of peripheral human CD4+CD25+ T cells that expresses CD45RO, histocompatibility leukocyte antigen DR, and intracellular cytotoxic T lymphocyte–associated antigen (CTLA) 4 does not expand after stimulation and markedly suppresses the expansion of conventional T cells in a contact-dependent manner. After activation, CD4+CD25+ T cells express CTLA-4 on the surface detectable for several weeks. These cells show a G1/G0 cell cycle arrest and no production of interleukin (IL)-2, IL-4, or interferon (IFN)-γ on either protein or mRNA levels. The anergic state of CD4+CD25+ T cells is not reversible by the addition of anti-CD28, anti–CTLA-4, anti–transforming growth factor β, or anti–IL-10 antibody. However, the refractory state of CD4+CD25+ T cells was partially reversible by the addition of IL-2 or IL-4. These data demonstrate that human blood contains a resident T cell population with potent regulatory properties.
Rheumatoid arthritis: treatment with azathioprine (IMURAN (R)). Clinical side-effects and laboratory abnormalities.
Authors: J K Whisnant, J Pelkey
Journal: Annals of the Rheumatic Diseases (1982)

A retrospective review of the literature has been carried out to determine laboratory abnormalities occurring in patients with rheumatoid arthritis (RA) treated with azathioprine, in order to establish a profile for this agent in the treatment of this disease. A total of 542 patients in 24 studies, reported in the literature, were given a range of doses of azathioprine for up to four years. Fifteen percent of patients were withdrawn because of toxicity. The two major toxic effects were gastrointestinal symptoms and alteration in blood counts. Clinically significant leucopenia (less than 2500/mm3) occurred in 14 of the total of 93 patients reported to have developed leucopenia. Some adverse reactions, which would have been expected from the use of azathioprine in other diseases, were uncommon, namely significant infections, hepatotoxicity and pancreatitis. Adverse experience with azathioprine in rheumatoid arthritis compares well with other slow-acting, or disease modifying, drugs.
Chromosome Patterns in Mouse Lung Tumors
Authors: Joseph A. Dipaolo
Journal: JNCI Journal of the National Cancer Institute (1965)

The chromosomal constitutions of spontaneous pulmonary adenomas of strain A mice and of pulmonary adenomas from strain A animals treated with urethan were analyzed in detail. Stemlines of the primary pulmonary adenomas were diploid, pseudodiploid, and aneuploid, with a preponderance of aneuploid. Tumors having a diploid mode also had cells with abnormal karyotypes. These observations emphasize that either a superficially normal or abnormal modal karyotype may be present at the preneoplastic stage. Serially transplanted adenomas underwent further alteration of stemlines which may or may not reflect tumor progression. Whether or not the abnormal chromosome constitutions have primary oncogenic significance, they may facilitate clonal selection during tumor progression.
The immunology of successful pregnancy
Authors: A.L. Veenstra van Nieuwenhoven
Journal: Human Reproduction Update (2003)

Immune responses play an important role in various reproductive processes, including ovulation, menstruation and parturition. Clearly, during pregnancy, when the mother must accept a semi‐allogeneic fetus, immune responses also play a very important role. This was first recognized by Medawar in 1953, when the concept of the fetal allograft was presented in order to explain the immunological relationship between mother and fetus. Since then, the immunology of pregnancy has been the leading subject within reproductive immunology research. Yet, the question of why the semi‐allogeneic fetus is not rejected by the mother remains unresolved. The present review provides an update of current knowledge on the subject of the so‐called ‘immunological paradox of pregnancy’.
FEMALE TO MALE TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1: RISK FACTORS FOR SEROCONVERSION IN MEN
Authors: D.William Cameron, LourdesJ D'Costa, GregoryM Maitha, Mary Cheang, Peter Piot, J.Neil Simonsen, AllanR Ronald, MichaelN Gakinya, J.O Ndinya-Achola, RobertC Brunham, FrancisA Plummer
Journal: The Lancet (1989)
Coordination of hypothalamic and pituitary T3 production regulates TSH expression
Authors: Tatiana L. Fonseca, Mayrin Correa-Medina, Maira P.O. Campos, Gabor Wittmann, Joao P. Werneck-de-Castro, Rafael Arrojo e Drigo, Magda Mora-Garzon, Cintia Bagne Ueta, Alejandro Caicedo, Csaba Fekete, Balazs Gereben, Ronald M. Lechan, Antonio C. Bianco
Journal: Journal of Clinical Investigation (2013)

Type II deiodinase (D2) activates thyroid hormone by converting thyroxine (T4) to 3,5,3'-triiodothyronine (T3). This allows plasma T4 to signal a negative feedback loop that inhibits production of thyrotropin-releasing hormone (TRH) in the mediobasal hypothalamus (MBH) and thyroid-stimulating hormone (TSH) in the pituitary. To determine the relative contributions of these D2 pathways in the feedback loop, we developed 2 mouse strains with pituitary- and astrocyte-specific D2 knockdown (pit-D2 KO and astro-D2 KO mice, respectively). The pit-D2 KO mice had normal serum T3 and were systemically euthyroid, but exhibited an approximately 3-fold elevation in serum TSH levels and a 40% reduction in biological activity. This was the result of elevated serum T4 that increased D2-mediated T3 production in the MBH, thus decreasing Trh mRNA. That tanycytes, not astrocytes, are the cells within the MBH that mediate T4-to-T3 conversion was defined by studies using the astro-D2 KO mice. Despite near-complete loss of brain D2, tanycyte D2 was preserved in astro-D2 KO mice at levels that were sufficient to maintain both the T4-dependent negative feedback loop and thyroid economy. Taken together, these data demonstrated that the hypothalamic-thyroid axis is wired to maintain normal plasma T3 levels, which is achieved through coordination of T4-to-T3 conversion between thyrotrophs and tanycytes.
2-(<sup>18</sup>F)-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Detects Clinical Relevant Adenomas of the Colon: A Prospective Study
Authors: Mariëtte C.A. van Kouwen, Fokko M. Nagengast, Jan B.M.J. Jansen, Wim J.G. Oyen, Joost P.H. Drenth
Journal: Journal of Clinical Oncology (2005)

Purpose 2-( 18 F)-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is a noninvasive imaging technique used clinically to detect malignant tumors. FDG-PET has been established as a tool for diagnosis of recurrent or metastatic colorectal carcinoma. Several case series suggest that FDG-PET also detects larger adenomas. The goal of this study was to investigate whether FDG-PET is able to detect colonic adenomas. Patients and Methods FDG-PET was performed in 100 consecutive patients in whom colonic adenomas were suspected on barium enema (n = 47) or sigmoidoscopy (n = 53). A positive scan was defined as focal large bowel FDG accumulation. FDG-PET was followed in all cases by colonoscopy, and removed adenomas were examined histopathologically. Results Colonoscopy confirmed the presence of adenomas in 68 of 100 patients. In 35 patients, there was focal FDG accumulation at site of the adenoma. The sensitivity of FDG-PET increased with adenoma size (21%, adenomas 1 to 5 mm; 47%, 6 to 10 mm; and 72%, &gt; 11 mm). The sensitivity of FDG-PET also increased with the grade of dysplasia (33%, low grade; 76%, high grade; and 89%, carcinomas). The overall specificity was 84%. Conclusion FDG-PET detects colonic adenomas and the diagnostic test characteristics improve with size and grade of dysplasia of the adenoma.
Hepatic precursors derived from murine embryonic stem cells contribute to regeneration of injured liver
Authors: Jeonghoon Heo, Valentina M. Factor, Tania Uren, Yasushi Takahama, Ju-Seog Lee, Marian Major, Stephen M. Feinstone, Snorri S. Thorgeirsson
Journal: Hepatology (2006)

We established an efficient system for differentiation, expansion and isolation of hepatic progenitor cells from mouse embryonic stem (ES) cells and evaluated their capacity to repopulate injured liver. Using mouse ES cells transfected with the green fluorescent protein (GFP) reporter gene regulated by albumin (ALB) enhancer/promoter, we found that a serum-free chemically defined medium supports formation of embryoid bodies (EBs) and differentiation of hepatic lineage cells in the absence of exogenous growth factors or feeder cell layers. The first GFP+ cells expressing ALB were detected in close proximity to "beating" myocytes after 7 days of EB cultures. GFP+ cells increased in number, acquired hepatocyte-like morphology and hepatocyte-specific markers (i.e., ALB, AAT, TO, and G6P), and by 28 days represented more than 30% of cells isolated from EB outgrowths. The FACS-purified GFP+ cells developed into functional hepatocytes without evidence of cell fusion and participated in the repairing of diseased liver when transplanted into MUP-uPA/SCID mice. The ES cell-derived hepatocytes were responsive to normal growth regulation and proliferated at the same rate as the host hepatocytes after an additional growth stimulus from CCl(4)-induced liver injury. The transplanted GFP+ cells also differentiated into biliary epithelial cells. In conclusion, a highly enriched population of committed hepatocyte precursors can be generated from ES cells in vitro for effective cell replacement therapy.
In Situ Measurements of Crossbridge Dynamics and Lattice Spacing in Rat Hearts by X-Ray Diffraction
Authors: James T. Pearson, Mikiyasu Shirai, Haruo Ito, Noriyuki Tokunaga, Hirotsugu Tsuchimochi, Naoki Nishiura, Daryl O. Schwenke, Hatsue Ishibashi-Ueda, Ryuichi Akiyama, Hidezo Mori, Kenji Kangawa, Hiroyuki Suga, Naoto Yagi
Journal: Circulation (2004)

Synchrotron radiation has been used to analyze crossbridge dynamics in isolated papillary muscle and excised perfused hearts with the use of x-ray diffraction techniques. We showed that these techniques can detect regional changes in rat left ventricle contractility and myosin lattice spacing in in situ ejecting hearts in real time. Furthermore, we examined the sensitivity of these indexes to regional ischemia.The left ventricular free wall of spontaneously beating rat hearts (heart rate, 290 to 404 bpm) was directly exposed to brief high-flux, low-emittance x-ray beams provided at SPring-8. Myosin mass transfer to actin filaments was determined as the decrease in reflection intensity ratio (intensity of 1,0 plane over the 1,1 plane) between end-diastole and end-systole. The distance between 1,0 reflections was converted to a lattice spacing between myosin filaments. We found that mass transfer (mean, 1.71+/-0.09 SEM, n=13 hearts) preceded significant increases in lattice spacing (2 to 5 nm) during systole in nonischemic pericardium. Left coronary occlusion eliminated increases in lattice spacing and severely reduced mass transfer (P<0.01) in the ischemic region.Our results suggest that x-ray diffraction techniques permit real-time in situ analysis of regional crossbridge dynamics at molecular and fiber levels that might also facilitate investigations of ventricular output regulation by the Frank-Starling mechanism.
THE ETIOLOGY OF BARTONELLA MURIS ANEMIA OF THE ALBINO RAT
Authors: J. Marmorston-Gottesman, David Perla
Journal: The Journal of Experimental Medicine (1932)

1. Bartonella muris has been isolated in pure culture on Noguchi's leptospira medium from the blood of the splenectomized adult rat suffering with Bartonella muris anemia. 2. Bartonella muris is a small, actively motile, Gram-negative bacillus. It grows best on media containing blood and on Noguchi's leptospira medium. The optimal temperature for growth is 20-25 degrees C. It produces neither gas nor acid on media containing sugars. It does not hemolyze blood in artificial media. Viability of the cultures in leptospira media was maintained for 36 days. 3. With this culture a severe anemia was produced in rats weighing 30 gm., with the occasional appearance of Bartonella muris bodies on the red cells. The anemia occurred within 24 hours, and lasted for 3 to 5 days with recovery of the rat. Bartonella muris was recovered in pure culture from the blood of these animals. The blood of these rats was infectious for other 30 gm. rats. 4. 3 week old rabbits were infected with cultures of Bartonella muris, a severe anemia resulting after an incubation period of 48 hours. The organism was recovered from the blood on the 5th day after injection. Bartonella muris is non-pathogenic for adult rabbits. 5. A severe anemia was produced in young guinea pigs with cultures of Bartonella muris within 48 hours. The organism was recovered on the 2nd and 5th days after injection. Postmortem examination revealed changes in the organs similar to those found in splenectomized rats suffering with spontaneous Bartonella muris anemia. 6. The infection was reproduced in white mice. In one instance a severe anemia developed on the 5th and 6th days. The organism was recovered on the 6th day. 7. The anemia was produced in splenectomized adult rats of non-carrier stock. The organism was recovered from the blood stream of these rats. A marked leukocytosis was noted (65,000) at the peak of the anemia as is found in the spontaneous disease in infected splenectomized adult rats. 8. Serological tests have thus far failed to demonstrate the production of agglutinins, though complement-fixing antibodies are present in homologous sera in low dilutions.
Is your pain really necessary?
Authors: P D Buisseret
Journal: BMJ (1973)

PatientsNormal Values Test Mean ± S.D. Mean + S.D. Euglobulin lysis time (units/ml) 2-7 + 1.1* 12-0 ± 5-3 Plasminogen (units/100 ml) .99 ± 22 100 ± 21Fibrinogen (mg/100 ml) .636± 192* 350 ± 84Factor VIII (%) .. 218 + 66* 104 ± 23 Antithrombin III (%) .108± 26 100 + 10 Thrombin time (sec) .18-0+ 3-2t
Biogenic Amine-Aldehyde Condensation Products: Tetrahydroisoquinolines and Tryptolines (szlig-Carbolines)
Authors: R Deitrich, V Erwin
Journal: The Annual Review of Pharmacology and Toxicology (1980)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More