tbuckley/cabot-search huggingface dataset:
Ground glass hepatocytes coexpressing hepatitis B virus X protein and surface antigens effect on oncogenic effects and tumorigenesis.
Authors: Ih-Jen Su, Han-Chieh Wu, Hung-Wen Tsai, Chiao-Fang Teng, Wen-Chuan Hsieh, Yih-Jyh Lin, Lily Hui-Ching Wang, Quan Yuan
Journal: Journal of Clinical Oncology (2014)

e15115 Background: Hepatitis B virus (HBV) X protein (HBx) and pre-S2 deletion mutant large surface antigens have been recognized as oncoproteins that induce hepatocellular carcinoma (HCC). The interaction of these two oncoproteins in the hepatocytes and its significance in tumorigenesis remains to be elucidated. Methods: In this study, a newly developed monoclonal antibody designed specifically against HBx was used for immunohistochemical and double-labeled immunofluorescence studies and the expression of HBx and surface antigens were evaluated. In vitro studies and transgenic mice models were used to evaluate the interaction and oncogenic effects of these two viral oncoproteins. Results: We observed the co-expression of HBx with surface antigens in ground glass hepatocytes in 5 of 20 hepatitis B surface antigen positive livers. In vitro, hepatocytes co-expressing HBx and pre-S2 mutant showed an enhanced expression of vascular endothelial growth factor-A (VEGF-A), phosphorylated Akt1/2/3 (p-Akt1/2/3), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and phosphorylated mammalian target of rapamycin (p-mTOR) signals. Transgenic mice harboring the double HBx and pre-S2 mutant construct plasmids developed HCCs at an average of 15.1 months, earlier than that of HBx (16.9 months) or pre-S2 mutant (24.5 months) alone. Interestingly, the oncogenic signals of VEGF-A, p-Akt1/2/3, p-ERK1/2, and p-mTOR were sequentially and differentially activated at different stages in the progression of tumorigenesis. Phosphorylated mTOR was consistently activated in transgenic and human HCCs. Conclusions: We conclude that ground glass hepatocytes co-expressing HBx and surface antigens may exhibit enhanced oncogenic effects and tumorigenesis in chronic HBV infections. The mTOR signal cascade may represent the key regulator in HBV tumorigenesis and is implicated for the design of HCC therapy.
Changes in suppressor mechanisms during postnatal development in mice.
Authors: C E Calkins, O Stutman
Journal: The Journal of Experimental Medicine (1978)

The activity of suppressor cells from spleens of mice of varying ages was assessed by their addition to cultures of normal or SRBC immune spleen cells together with a challenge of SRBC. 1-wk and adult spleen cells were highly suppressive of the secondary in vitro antibody response to SRBC. 3-wk spleen cells were less active in suppressing this response. The nature of the suppression and the character of the suppressor cells changed in this period. Whereas adult spleen cells demonstrated specificity, 1-wk cells nonspecifically suppressed all responses tested. Further, unlike adult suppressor cells (which are Thy.1.2 positive), 1-wk suppressor cells are insensitive to anti-Thy.1.2 treatment in this system. Both cells are nonadherent to glass beads and nylon wool and are undetectable in the normal thymus.
Immunological and physical properties of allergen solutions
Authors: L. Frølund, L. K. Poulsen, J. H. Heinig, U. G. Svedse, F. Madsen
Journal: Allergy (1991)

Lyophilised birch pollen allergen extracts, reconstituted with different diluents (H 2 O, saline, Albumin diluent® (AD)) were investigated to determine whether the allergen activity and quality of the extracts deteriorated by nebulization with different nebulizers (Pari, Wright, and Samdoz). Allergen activity was measured by IgG 4 RAST inhibition technique and allergen quality was analysed by crossed immunoelectrophoresis (CIE). The distribution of particle sizes of aerosols different allergen solutions was determined by a TSI Aerodynamic Particle Sizer. A significant difference ( P &lt; 0.05) in allergen activity was found between the AD and H 2 O diluents before and after using a Sandoz nebulizer and a Wright nebulizer equipped with a small chamber. This suggested greater allergen activity in AD‐diluted solutions, and the pattern was repeated with the other two nebulizers, but was not statistically significant. The samples diluted with saline showed no significant differences in quality after nebulization except for the impacted aerosol in which one of the precipitates was slightly diminished. In the AD‐diluted sample one of the precipitates disappeared from the impacted aerosol and from the nebulization chamber after 2 min nebulization. To CIE with rabbit anti‐human albumin in an intermediate gel. By this procedure one precipitate was transformed to a precipitate in the intermediate gel, indicating that one or more proteins in the extracts may associate with albumin. No significant difference in output was observed between the nebulizers. The particle size distribution curves for each diluent (saline, AD) were identical for the Wright nebulizer with 99% of the dry particles distributed within 0.5–2.0 μm. Although allergen solutions reconstituted with different diluents were not deteriorated in different nebulizers, it may be that the addition of human albumin to an allergen solution may induce one or more proteins in the extracts to associate with it. This could reduce allergen adsorption over periods longer than this study. The use of different diluents did not change the distribution of particle size generated by the nebulizer tested.
Is excessive infant crying an honest signal of vigor, one extreme of a continuum, or a strategy to manipulate parents?
Authors: Edward H. Hagen
Journal: Behavioral and Brain Sciences (2004)

An evolutionary account of excessive crying in young infants – colic – has been elusive. A study of mothers with new infants suggests that more crying is associated with more negative emotions towards the infant, and perceptions of poorer infant health. These results undermine the hypothesis that excessive crying is an honest signal of vigor.
Reciprocal Regulation of Aquaporin-2 Abundance and Degradation by Protein Kinase A and p38-MAP Kinase
Authors: Pavel I. Nedvetsky, Vedrana Tabor, Grazia Tamma, Sven Beulshausen, Philipp Skroblin, Aline Kirschner, Kerim Mutig, Mareike Boltzen, Oscar Petrucci, Anna Vossenkämper, Burkhard Wiesner, Sebastian Bachmann, Walter Rosenthal, Enno Klussmann
Journal: Journal of the American Society of Nephrology (2010)

Arginine-vasopressin (AVP) modulates the water channel aquaporin-2 (AQP2) in the renal collecting duct to maintain homeostasis of body water. AVP binds to vasopressin V2 receptors (V2R), increasing cAMP, which promotes the redistribution of AQP2 from intracellular vesicles into the plasma membrane. cAMP also increases AQP2 transcription, but whether altered degradation also modulates AQP2 protein levels is not well understood. Here, elevation of cAMP increased AQP2 protein levels within 30 minutes in primary inner medullary collecting duct (IMCD) cells, in human embryonic kidney (HEK) 293 cells ectopically expressing AQP2, and in mouse kidneys. Accelerated transcription or translation did not explain this increase in AQP2 abundance. In IMCD cells, cAMP inhibited p38-mitogen-activated protein kinase (p38-MAPK) via activation of protein kinase A (PKA). Inhibition of p38-MAPK associated with decreased phosphorylation (serine 261) and polyubiquitination of AQP2, preventing proteasomal degradation. Our results demonstrate that AVP enhances AQP2 protein abundance by altering its proteasomal degradation through a PKA- and p38-MAPK-dependent pathway.
Association between HLA-DR antigens and rheumatoid arthritis in Arabs.
Authors: M A Sattar, M al-Saffar, R T Guindi, T N Sugathan, K Behbehani
Journal: Annals of the Rheumatic Diseases (1990)

Eighty five Arab patients with classical and definite rheumatoid arthritis were typed to determine the prevalence of HLA A, B, C, and DR antigens. A significant increase in the prevalence of HLA-A10, B8, B21, and DR3 was found in comparison with a control population matched for age and sex. HLA-DR5 was significantly decreased in the patient group. The classical association of HLA-DR4 with rheumatoid arthritis could not be confirmed in the Arab patients resident in Kuwait, supporting reported observations in different ethnic groups of associations with HLA antigens other than HLA-DR4 and indicating a heterogeneous genetic susceptibility to rheumatoid arthritis.
THE PRODUCTION OF ANTIBODIES IN RABBITS BY A SIMPLIFIED INTRATRACHEAL METHOD
Authors: F. S. Jones
Journal: The Journal of Experimental Medicine (1923)

The method described of producing antibodies by the administration of antigens through the larynx is simple. The results obtained, however, conform closely to those obtained through intraperitoneal injection. The procedure is relatively a safe one and may well be employed in experimental inoculations. The advantages of rapidity and painlessness are obvious. In addition, gross injury has not been observed. Injections may be repeated at frequent intervals without danger to the life of the animal. The tube illustrated in Text-fig. 1 extends a little over 1 cm. into the trachea. The tube designed for the guinea pig reaches 2 or 3 mm. below the glottis. While the doses indicated in the protocols are small, 7 to 10 cc. of liquid have been given to rabbits by means of the tube without ill effects. It has been shown by the injection of India ink that the material is well distributed throughout the lungs in both the rabbit and guinea pig. Under certain conditions it may be advisable to inject more deeply into the trachea, especially in the rabbit. The tube illustrated in Text-fig. 1 is not adaptable for this purpose. A cannula of larger diameter has proved of distinct advantage as a shield for introducing flexible catheters well down the trachea. A cannula 9 cm. long and 4 mm. in diameter when bent at an angle of 45 degrees may be passed through the larynx of a rabbit without difficulty. A No. 8 (French) woven or No. 10 soft rubber catheter may be inserted into the cannula beyond the bend before the tube is passed through the glottis. After the tube has entered the glottis the catheter then may be introduced as deeply as desired into the teachea. The metal cannula enables the operator to "feel" the glottis. From the experiments one seems justified in concluding that the results obtained by administering antigens by way of the trachea are about the same as those obtained by the intraperitoneal route. With the tubes described injury has been largely eliminated. The procedure is relatively a safe one.
A phase II study on metastatic breast cancer patients treated with weekly vinorelbine with or without trastuzumab according to HER2 expression: changing the natural history of HER2-positive disease
Authors: P. Papaldo, A. Fabi, G. Ferretti, M. Mottolese, A.M. Cianciulli, B. Di Cocco, M.S. Pino, P. Carlini, S. Di Cosimo, I. Sacchi, I. Sperduti, C. Nardoni, F. Cognetti
Journal: Annals of Oncology (2006)
Elastin Degradation and Calcification in an Abdominal Aorta Injury Model
Authors: Dina M. Basalyga, Dan T. Simionescu, Wanfen Xiong, B. Timothy Baxter, Barry C. Starcher, Narendra R. Vyavahare
Journal: Circulation (2004)

Background— Elastin calcification is a widespread feature of vascular pathology, and circumstantial evidence exists for a correlation between elastin degradation and calcification. We hypothesized that matrix metalloproteinase (MMP)–mediated vascular remodeling plays a significant role in elastin calcification. Methods and Results— In the present studies, we determined that short-term periadventitial treatment of the rat abdominal aorta with low concentrations of calcium chloride (CaCl 2 ) induced chronic degeneration and calcification of vascular elastic fibers in the absence of aneurysm formation and inflammatory reactions. Furthermore, the rate of progression of calcification depended on the application method and concentration of CaCl 2 applied periarterially. Initial calcium deposits, associated mainly with elastic fibers, were persistently accompanied by elastin degradation, disorganization of aortic extracellular matrix, and moderate levels of vascular cell apoptosis. Application of aluminum ions (known inhibitors of elastin degradation) before the CaCl 2 -mediated injury significantly reduced elastin calcification and abolished both extracellular matrix degradation and apoptosis. We also found that MMP-knockout mice were resistant to CaCl 2 -mediated aortic injury and did not develop elastin degeneration and calcification. Conclusion— Collectively, these data strongly indicate a correlation between MMP-mediated elastin degradation and vascular calcification.
Prostate cancer: ESMO Consensus Conference Guidelines 2012
Authors: A. Horwich, J. Hugosson, T. de Reijke, T. Wiegel, K. Fizazi, V. Kataja, Chris Parker, Joaquim Bellmunt, Dominik Berthold, Anna Bill-Axelson, Sigrid Carlsson, Gedske Daugaard, Gert De Meerleer, Theo de Reijke, David Dearnaley, Karim Fizazi, Valérie Fonteyne, Silke Gillessen, Daniel Heinrich, Alan Horwich, Jonas Hugosson, Vesa Kataja, Maciej Kwiatkowski, Sten Nilsson, Anwar Padhani, Christos Papandreou, Chris Parker, Monique Roobol, Avishay Sella, Riccardo Valdagni, Theo Van der Kwast, Paul Verhagen, Thomas Wiegel
Journal: Annals of Oncology (2013)
A 5′ Regulatory Sequence Containing Two Ets Motifs Controls the Expression of the Wiskott-Aldrich Syndrome Protein (WASP) Gene in Human Hematopoietic Cells
Authors: A. Petrella, I. Doti, V. Agosti, P. Carandente Giarrusso, D. Vitale, H.M. Bond, C. Cuomo, P. Tassone, B. Franco, A. Ballabio, S. Venuta, G. Morrone
Journal: Blood (1998)
Effects of Promoting Longer-Term and Exclusive Breastfeeding on Cardiometabolic Risk Factors at Age 11.5 Years
Authors: Richard M. Martin, Rita Patel, Michael S. Kramer, Konstantin Vilchuck, Natalia Bogdanovich, Natalia Sergeichick, Nina Gusina, Ying Foo, Tom Palmer, Jennifer Thompson, Matthew W. Gillman, George Davey Smith, Emily Oken
Journal: Circulation (2013)

The duration and exclusivity of breastfeeding in infancy have been inversely associated with future cardiometabolic risk. We investigated the effects of an experimental intervention to promote increased duration of exclusive breastfeeding on cardiometabolic risk factors in childhood.
Real-Time Quantitative Polymerase Chain Reaction Detection of Minimal Residual Disease by Standardized <i>WT1</i> Assay to Enhance Risk Stratification in Acute Myeloid Leukemia: A European LeukemiaNet Study
Authors: Daniela Cilloni, Aline Renneville, Fabienne Hermitte, Robert K. Hills, Sarah Daly, Jelena V. Jovanovic, Enrico Gottardi, Milena Fava, Susanne Schnittger, Tamara Weiss, Barbara Izzo, Josep Nomdedeu, Adrian van der Heijden, Bert A. van der Reijden, Joop H. Jansen, Vincent H.J. van der Velden, Hans Ommen, Claude Preudhomme, Giuseppe Saglio, David Grimwade
Journal: Journal of Clinical Oncology (2009)

Purpose Risk stratification in acute myeloid leukemia (AML) is currently based on pretreatment characteristics. It remains to be established whether relapse risk can be better predicted through assessment of minimal residual disease (MRD). One proposed marker is the Wilms tumor gene WT1, which is overexpressed in most patients with AML, thus providing a putative target for immunotherapy, although in the absence of a standardized assay, its utility for MRD monitoring remains controversial. Patients and Methods Nine published and in-house real-time quantitative polymerase chain reaction WT1 assays were systematically evaluated within the European LeukemiaNet; the best-performing assay was applied to diagnostic AML samples (n = 620), follow-up samples from 129 patients treated with intensive combination chemotherapy, and 204 normal peripheral blood (PB) and bone marrow (BM) controls. Results Considering relative levels of expression detected in normal PB and BM, WT1 was sufficiently overexpressed to discriminate ≥ 2-log reduction in transcripts in 46% and 13% of AML patients, according to the respective follow-up sample source. In this informative group, greater WT1 transcript reduction after induction predicted reduced relapse risk (hazard ratio, 0.54 per log reduction; 95% CI, 0.36 to 0.83; P = .004) that remained significant when adjusted for age, WBC count, and cytogenetics. Failure to reduce WT1 transcripts below the threshold limits defined in normal controls by the end of consolidation also predicted increased relapse risk (P = .004). Conclusion Application of a standardized WT1 assay provides independent prognostic information in AML, lending support to incorporation of early assessment of MRD to develop more robust risk scores, to enhance risk stratification, and to identify patients who may benefit from allogeneic transplantation.
Diagnosis of pulmonary thromboembolism with endobronchial ultrasound
Authors: G. L. Casoni, C. Gurioli, M. Romagnoli, V. Poletti
Journal: European Respiratory Journal (2008)

To the Editors: 

Endobronchial ultrasound (EBUS) is a new addition to the diagnostic armamentaria of the pneumologist. Its properties allow for excellent visualisation of structures surrounding the airways and, as such, have significant potential to add to diagnostic bronchoscopies. EBUS has a definitive role in detection and biopsy of mediastinal lymph nodes or masses 1, 2. However, we believe that the potential use of this procedure is still underestimated. For this reason, in this letter we report on the …
New Epidemiology of Human Papillomavirus Infection and Cervical Neoplasia
Authors: M. H. Schiffman
Journal: JNCI Journal of the National Cancer Institute (1995)

20) Powles TJ, Jones AL, Ashley SE.O'Brien ME.Tidy VA, Treleavan J, et al.The Royal Marsen Hospital pilot tamoxifen chemoprevention trial.
The mouse mahoganoid coat color mutation disrupts a novel C3HC4 RING domain protein
Authors: Loan K. Phan, Feng Lin, Charles A. LeDuc, Wendy K. Chung, Rudolph L. Leibel
Journal: Journal of Clinical Investigation (2002)

The mouse coat color mutant mahoganoid (md) darkens coat color and decreases the obesity of Ay mice that ectopically overexpress agouti-signaling protein. The phenotypic effects of md are similar to those of the recently identified coat color mutant mahogany (Atrnmg). We report the positional cloning of mahoganoid, encoding a novel 494–amino acid protein containing a C3HC4 RING (really interesting new gene) domain that may function as an E3 ubiquitin ligase. The mutations in the mahoganoid allelic series (md, md2J, md5J) are all due to large retroviral insertions. In md and md2J, the result is minimal expression of the normal size transcripts in all tissues examined. Unlike Atrnmg/Atrnmg animals, we observe no evidence of neurological deficit or neuropathology in md/md mice. Body weight and body mass index (a surrogate for adiposity) measurements of B6.C3H-md-A md/+ and md/md animals on 9% and 45% kcal fat diets indicate that mahoganoid does not suppress body weight in B6.C3H animals in a gene dose-dependent fashion.
Pregnancy Outcome Following First-Trimester Exposure to Fluoxetine (Prozac)
Authors: Anne Pastuszak
Journal: JAMA (1993)

To compare pregnancy outcome following first-trimester fluoxetine (Prozac) exposure with pregnancy outcome in two matched control groups. Fluoxetine is a new antidepressant used by many young women. Currently, no published data exist on its safety in pregnancy.We prospectively collected and followed up 128 pregnant women exposed to a mean daily dose of 25.8 mg (+/- 13 mg) of fluoxetine during the first trimester and compared pregnancy outcome with two matched groups of women exposed during the first trimester of pregnancy to either nonteratogens or tricyclic antidepressants.Rates of major malformations were comparable within the three groups and did not exceed those expected in the general population. Women treated with fluoxetine had a tendency for increased risk for miscarriage when compared with women exposed to nonteratogens (relative risk, 1.9; 95% confidence interval, 0.92 to 3.92). The rate of miscarriages in the fluoxetine group was comparable with the tricyclic group (13.5% and 12.2% vs 6.8% in the nonteratogens).Our study suggests that the use of fluoxetine during embryogenesis is not associated with an increased risk of major malformations. Women exposed to both fluoxetine and tricyclic antidepressants tended to report higher rates of miscarriage; further studies will be needed to confirm this observation and to separate the effects of the psychiatric condition from the associated drugs. Long-term studies will be warranted to rule out potential developmental teratology of fluoxetine, which affects a central nervous system neurotransmitter.
Heterozygous Cellular Glutathione Peroxidase Deficiency in the Mouse
Authors: Marc A. Forgione, Andre Cap, Ronglih Liao, Nicanor I. Moldovan, Robert T. Eberhardt, Chee Chew Lim, John Jones, Pascal J. Goldschmidt-Clermont, Joseph Loscalzo
Journal: Circulation (2002)

Background— Oxidant stress has been implicated in the pathogenesis of atherothrombosis and other vascular disorders accompanied by endothelial dysfunction. Glutathione peroxidases (GPx) play an important role in the cellular defense against oxidant stress by utilizing glutathione (GSH) to reduce lipid hydroperoxides and hydrogen peroxide to their corresponding alcohols. Cellular GPx (GPx-1) is the principal intracellular isoform of GPx. We hypothesized that GPx-1 deficiency per se induces endothelial dysfunction and structural vascular abnormalities through increased oxidant stress. Methods and Results— A murine model of heterozygous deficiency of GPx-1 (GPx +/−) was investigated to examine this hypothesis. Mesenteric arterioles in GPx-1 +/− mice demonstrated vasoconstriction to acetylcholine compared with vasodilation in wild-type mice (maximal change in vessel diameter, −13.0±2.8% versus 13.2±2.8%, P &lt;0.0001). We also noted an increase in the plasma and aortic levels of the isoprostane iPF 2α -III, a marker of oxidant stress, in GPx-1 +/− mice compared with wild-type mice (170.4±23 pg/mL plasma versus 98.7±7.1 pg/mL plasma, P &lt;0.03; 11.7±0.87 pg/mg aortic tissue versus 8.2±0.55 pg/mg aortic tissue, P &lt;0.01). Histological sections from the coronary vasculature of GPx-1 +/− mice show increased perivascular matrix deposition, an increase in the number of adventitial fibroblasts, and intimal thickening. These structural abnormalities in the myocardial vasculature were accompanied by diastolic dysfunction after ischemia-reperfusion. Conclusions— These findings demonstrate that heterozygous deficiency of GPx-1 leads to endothelial dysfunction, possibly associated with increased oxidant stress, and to significant structural vascular and cardiac abnormalities. These data illustrate the importance of this key antioxidant enzyme in functional and structural responses of the mammalian cardiovascular system.