tbuckley/cabot-search huggingface dataset:
Effect of Combined Folic Acid, Vitamin B6, and Vitamin B12 on Colorectal Adenoma
Authors: Yiqing Song, JoAnn E. Manson, I-Min Lee, Nancy R. Cook, Ligi Paul, Jacob Selhub, Edward Giovannucci, Shumin M. Zhang
Journal: JNCI Journal of the National Cancer Institute (2012)

Folic acid, vitamin B6, and vitamin B12 act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma. The Women's Antioxidant and Folic Acid Cardiovascular Study was a randomized, double-blind, placebo-controlled trial of 5442 female health professionals at high risk for cardiovascular disease from April 1998 through July 2005. Participants were randomly assigned to receive a combination pill of folic acid (2.5mg), vitamin B6 (50mg), and vitamin B12 (1mg) or placebo. This study included 1470 participants who were followed up for as long as 9.2 years and underwent an endoscopy at any point during follow-up. We estimated relative risks using a generalized linear model with a natural logarithm link function and Poisson distributed errors. All statistical tests were two-sided. The risk of colorectal adenoma was similar among participants receiving treatment (24.3%, 180 of 741 participants) vs placebo (24.0%, 175 of 729 participants) (multivariable adjusted relative risk = 1.00, 95% confidence interval = 0.83 to 1.20). Treatment was not associated with the risk of adenoma when data were analyzed by subsite, size, stage, and the number of adenomas. There was no statistically significant effect modification by alcohol intake, history of cancer or adenoma, or baseline plasma levels or intakes of folate, vitamin B6, or vitamin B12. Our results indicate no statistically significant effect of combined folic acid, vitamin B6, and vitamin B12 treatment on colorectal adenoma among women at high risk for cardiovascular disease.
Fcγ Receptor III and Fcγ Receptor IV on Macrophages Drive Autoimmune Valvular Carditis in Mice
Authors: Patricia M. Hobday, Jennifer L. Auger, Gregory R. Schuneman, Stefanie Haasken, J. Sjef Verbeek, Bryce A. Binstadt
Journal: Arthritis & Rheumatology (2013)

Objective Arthritis and valvular carditis coexist in several human rheumatic diseases, including systemic lupus erythematosus, rheumatic fever, and rheumatoid arthritis. T cell receptor–transgenic K/BxN mice develop spontaneous autoantibody‐associated arthritis and valvular carditis. The common Fc receptor γ (FcRγ) signaling chain is required for carditis to develop in K/BxN mice. FcRγ pairs with numerous receptors in a variety of cells. The aim of this study was to identify the FcRγ‐associated receptors and Fcγ receptor (FcγR)–expressing cells that mediate valvular carditis in this model. Methods We bred K/BxN mice lacking the genes that encode activating Fcγ receptors (FcγRI, FcγRIII, and FcγRIV), and we assessed these mice for valvular carditis. We similarly evaluated complement component C3–deficient K/BxN mice. Immunohistochemistry, bone marrow transplantation, and macrophage depletion were used to define the key FcRγ‐expressing cell type. Results Genetic deficiency of only one of the activating Fcγ receptors did not prevent carditis, whereas deficiency of all 3 activating Fcγ receptors did. Further analysis demonstrated that FcγRIII and FcγRIV were the key drivers of valve inflammation; FcγRI was dispensable. C3 was not required. FcRγ expression by radioresistant cells was critical for valvular carditis to develop, and further analysis indicated that macrophages were the key candidate FcγR‐expressing effectors of carditis. Conclusion FcγRIII and FcγRIV act redundantly to promote valvular carditis in K/BxN mice with systemic autoantibody‐associated arthritis. Macrophage depletion reduced the severity of valve inflammation. These findings suggest that pathogenic autoantibodies engage Fcγ receptors on macrophages to drive valvular carditis. Our study provides new insight into the pathogenesis of cardiovascular inflammation in the setting of autoantibody‐associated chronic inflammatory diseases.
Non-invasive measurement of small-bowel motility by MRI after abdominal surgery
Authors: M. A Patak, J. M Froehlich, C. von Weymarn, S. Breitenstein, C. L Zollikofer, K.-U. Wentz
Journal: Gut (2007)

Abdominal surgery under general anaesthesia causes postoperative ileus1 with an extended recovery time.2 Prolonged ileus creates major healthcare problems costing an estimated US$ 750 million per annum (£382 million, €563 million) in the US.3 Small-bowel motility is currently assessed by manometry, small-bowel transit time of radio-opaque markers and scintigraphy.4 All these methods are invasive (tube, radio-opaque markers or radio-labelled meal), unpopular with patients and restricted in their application to a few academic centres. Ultrafast magnetic resonance imaging (MRI) allows dynamic analysis of moving structures under physiological conditions, as reported for other organs.5,6

In this prospective clinical study, 30 patients were examined 3–5 days after colorectal surgery (sigmoidectomy (n = 20), diverticulitis or carcinoma; rectal resection (n = 8), carcinoma). Surgeries were performed under general anaesthesia combined with peridural block analgesia. For MRI (1.5 T), no oral preparation was administered …
T cell receptor zeta/CD3-p59fyn(T)-associated p120/130 binds to the SH2 domain of p59fyn(T).
Authors: A J da Silva, O Janssen, C E Rudd
Journal: The Journal of Experimental Medicine (1993)

Intracellular signaling from the T cell receptor (TCR)zeta/CD3 complex is likely to be mediated by associated protein tyrosine kinases such as p59fyn(T), ZAP-70, and the CD4:p56lck and CD8:p56lck coreceptors. The nature of the signaling cascade initiated by these kinases, their specificities, and downstream targets remain to be elucidated. The TCR-zeta/CD3:p59fyn(T) complex has previously been noted to coprecipitate a 120/130-kD doublet (p120/130). This intracellular protein of unknown identity associates directly with p59fyn(T) within the receptor complex. In this study, we have shown that this interaction with p120/130 is specifically mediated by the SH2 domain (not the fyn-SH3 domain) of p59fyn(T). Further, based on the results of in vitro kinase assays, p120/130 appears to be preferentially associated with p59fyn(T) in T cells, and not with p56lck. Antibody reprecipitation studies identified p120/130 as a previously described 130-kD substrate of pp60v-src whose function and structure is unknown. TCR-zeta/CD3 induced activation of T cells augmented the tyrosine phosphorylation of p120/130 in vivo as detected by antibody and GST:fyn-SH2 fusion proteins. p120/130 represents the first identified p59fyn(T):SH2 binding substrate in T cells, and as such is likely to play a key role in the early events of T cell activation.
Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile
Authors: Leonardo Rossi, Alessandra Salvetti, Francesco M Marincola, Annalisa Lena, Paolo Deri, Linda Mannini, Renata Batistoni, Ena Wang, Vittorio Gremigni
Journal: Genome biology (2007)

Abstract Background Mammalian stem cells are difficult to access experimentally; model systems that can regenerate offer an alternative way to characterize stem cell related genes. Planarian regeneration depends on adult pluripotent stem cells - the neoblasts. These cells can be selectively destroyed using X-rays, enabling comparison of organisms lacking stem cells with wild-type worms. Results Using a genomic approach we produced an oligonucleotide microarray chip (the Dj600 chip), which was designed using selected planarian gene sequences. Using this chip, we compared planarians treated with high doses of X-rays (which eliminates all neoblasts) with wild-type worms, which led to identification of a set of putatively neoblast-restricted genes. Most of these genes are involved in chromatin modeling and RNA metabolism, suggesting that epigenetic modifications and post-transcriptional regulation are pivotal in neoblast regulation. Comparing planarians treated with low doses of X-rays (after which some radiotolerant neoblasts re-populate the planarian body) with specimens irradiated with high doses and unirradiated control worms, we identified a group of genes that were upregulated as a consequence of low-dose X-ray treatment. Most of these genes encode proteins that are known to regulate the balance between death and survival of the cell; our results thus suggest that genetic programs that control neoblast cytoprotection, proliferation, and migration are activated by low-dose X-rays. Conclusion The broad differentiation potential of planarian neoblasts is unparalleled by any adult stem cells in the animal kingdom. In addition to our validation of the Dj600 chip as a valuable platform, our work contributes to elucidating the molecular mechanisms that regulate the self-renewal and differentiation of neoblasts.
Serum markers of hepatitis B virus replication, liver histology and intrahepatic expression of hepatitis B core antigen
Authors: Fernando Ramalho, Maurizia R. Brunetto, Giuseppe Rocca, Giovanna Giuliani Piccari, Amelia Batista, Elisabetta Chiaberge, Carla Lavarini, Roberto P. Dal Monte, Miguel Carneiro de Moura, Ferruccio Bonino
Journal: Journal of Hepatology (1988)
Quinidine is a competitive antagonist at alpha 1- and alpha 2-adrenergic receptors.
Authors: H J Motulsky, A S Maisel, M D Snavely, P A Insel
Journal: Circulation Research (1984)

Although quinidine is known to have antiadrenergic effects in the cardiovascular system, the precise mechanism by which it exerts these effects is not well defined. We asked whether quinidine binds directly to adrenergic receptors. Radioligand-binding assays were used to identify alpha 1-adrenergic receptors [( 3H]prazosin-binding sites) on membranes prepared from rat heart and kidney, alpha 2-adrenergic receptor [( 3H]yohimbine-binding sites) on human platelets and rat kidney membranes, and beta-adrenergic receptors [( 125I]iodocyanopindolol-binding sites) on rat heart and kidney membranes. Although it did not effectively compete for binding to beta-adrenergic receptors, quinidine competed for binding to alpha 1- and alpha 2-adrenergic receptors and yielded equilibrium dissociation constants of 0.3-3 microM. Two other antiarrhythmic agents, lidocaine and procainamide, did not compete for binding to alpha-adrenergic receptors. Further experiments demonstrated that the interactions of quinidine with the cardiac alpha 1- and platelet alpha 2-adrenergic receptors were competitive and reversible. We conclude that that antiadrenergic actions of quinidine can be explained by occupancy and competitive blockade of alpha 1- and alpha 2-adrenergic receptors.
Interleukin 4 inhibits the proliferation but not the differentiation of activated human B cells in response to interleukin 2.
Authors: T Defrance, B Vanbervliet, J P Aubry, J Banchereau
Journal: The Journal of Experimental Medicine (1988)

The combined effect of IL-4 and IL-2 on proliferation of anti-IgM antibody or Staphylococcus aureus strain Cowan I (SAC)-preactivated B cells was investigated. It was observed that in most cases, rIL-2 used at optimal concentration induced higher levels of tritiated thymidine ([3H]TdR) uptake than rIL-4 used at optimal concentration. When rIL-4 and rIL-2 were added together, it was repeatedly found that B cell proliferation induced by rIL-2 was significantly reduced and was, in most cases, comparable with the proliferation induced by rIL-4 alone. Cell cycle studies demonstrated that rIL-4 significantly reduced the number of cells entering S and G2/M phases of the cell cycle upon rIL-2 stimulation. B cell blasts preincubated for 24 or 48 h with rIL-4 displayed a reduced proliferation in response to rIL-2. In contrast, preculture of resting B cells with rIL-4 did not impair their subsequent proliferation in response to rIL-2 plus insolubilized anti-IgM antibody. This suggests that rIL-4 can only exert its inhibitory effect once B cells have received an activation signal. The differentiative activity of rIL-2 measured on B cell blasts preactivated for 2 d with SAC was not altered by rIL-4, which suggests that rIL-4 did not exert its inhibitory activity on rIL-2-induced B cell proliferation by enhancing rIL-2-mediated differentiation. Delayed addition of a neutralizing anti-IL-4 antiserum demonstrated that a period of contact of at least 24 h between IL-4 and B cell blasts was necessary for the development of the antagonistic effect of IL-4 on IL-2-mediated growth of activated B cells. These data demonstrate that IL-4 antagonizes the B cell growth-promoting effect of IL-2 without affecting the differentiation of preactivated B cells in response to IL-2.
Burden of Total and Cause-Specific Mortality Related to Tobacco Smoking among Adults Aged ≥45 Years in Asia: A Pooled Analysis of 21 Cohorts
Authors: Wei Zheng, Dale F. McLerran, Betsy A. Rolland, Zhenming Fu, Paolo Boffetta, Jiang He, Prakash Chandra Gupta, Kunnambath Ramadas, Shoichiro Tsugane, Fujiko Irie, Akiko Tamakoshi, Yu-Tang Gao, Woon-Puay Koh, Xiao-Ou Shu, Kotaro Ozasa, Yoshikazu Nishino, Ichiro Tsuji, Hideo Tanaka, Chien-Jen Chen, Jian-Min Yuan, Yoon-Ok Ahn, Keun-Young Yoo, Habibul Ahsan, Wen-Harn Pan, You-Lin Qiao, Dongfeng Gu, Mangesh Suryakant Pednekar, Catherine Sauvaget, Norie Sawada, Toshimi Sairenchi, Gong Yang, Renwei Wang, Yong-Bing Xiang, Waka Ohishi, Masako Kakizaki, Takashi Watanabe, Isao Oze, San-Lin You, Yumi Sugawara, Lesley M. Butler, Dong-Hyun Kim, Sue K. Park, Faruque Parvez, Shao-Yuan Chuang, Jin-Hu Fan, Chen-Yang Shen, Yu Chen, Eric J. Grant, Jung Eun Lee, Rashmi Sinha, Keitaro Matsuo, Mark Thornquist, Manami Inoue, Ziding Feng, Daehee Kang, John D. Potter
Journal: PLoS Medicine (2014)

Background Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest. Methods and Findings We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan—accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37–1.51) and 1.48-fold (1.38–1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%–17.2%) and 3.3% (2.6%–4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000–1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y. Conclusions Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors' Summary
Secondary Hyperpigmentation During Interferon Alfa Treatment for Chronic Hepatitis C Virus Infection
Authors: Katerina Tsilika, Albert Tran, Régine Trucchi, Sinziana Pop, Rodolphe Anty, Nathalie Cardot-Leccia, Jean-Philippe Lacour, Jean-Paul Ortonne, Thierry Passeron
Journal: JAMA Dermatology (2013)

Interferon alfa remains the central treatment for chronic hepatitis C virus (HCV) infection. Cases of cutaneous and mucous hyperpigmentations during interferon alfa treatment have been reported, but they are considered rare adverse effects.To study the clinical presentation and frequency of hyperpigmentation in patients receiving interferon alfa treatment for chronic HCV infection.Prospective, descriptive clinical trial.Monocentric study performed in the Departments of Hepatology and Dermatology of the University Hospital of Nice, Nice, France.Consecutive patients treated with pegylated interferon alfa-2b and ribavirin for chronic HCV infection.Demographic data and medical history were noted. A systematic clinical and dermoscopic examination of skin, nails, and mucous membranes was performed, and skin biopsies were performed if needed.Of 77 patients who were included, 16 (21%) presented with hyperpigmentation. Hyperpigmentation of the oral mucous membrane, acquired longitudinal melononychia, and hyperpigmentation of the face were each observed in 7 patients (9%). All patients with hyperpigmentation of the skin had skin type III or IV and worked outside without sun protection. The intensity of pigmentation was reported to decrease progressively when interferon treatment was discontinued. Most patients with hyperpigmentation of the oral mucosa also had melanonychia. However, patients with hyperpigmentation of the skin did not have mucosal or nail involvement, suggesting 2 distinct mechanisms.Secondary hyperpigmentation during interferon alfa treatment occurs as an adverse event in 21% of patients, especially in those with dark skin types who have unprotected sun exposure. Physicians should be aware of the adverse effects of interferon treatment and advise patients in the use of sun protection, especially patients with darker skin types.
Further characterization of NADPH oxidase activity of human polymorphonuclear leukocytes.
Authors: L C McPhail, L R DeChatelet, P S Shirley
Journal: Journal of Clinical Investigation (1976)

Mn2+ was shown to catalyze a nonenzymatic oxidation of NADPH in the presence of superoxide anion by means of an isotopic assay for measurement of the oxidation of NADPH to NADP+. Human polymorphonuclear leukocyte granule NADPH oxidase activity was evaluated in the absence of Mn2+ and was found to be higher in granules from phagocytizing cells than in granules from resting cells. The drug phorbol myristate acetate, which affects the oxidative metabolism of the neutrophil like phagocytosis, was found to activate granule NADPH oxidase activity. Superoxide dismutase was shown to inhibit NADPH oxidase activity both in the presence and absence of added Mn2+. The NADPH oxidase reaction in the absence of Mn2+ was optimal at pH 5.5, and was more linear with increasing time and protein concentration than in the presence of Mn2+. No activity was measurable in granules isolated from resting cells until the level of NADPH added was above 0.25 mM. Activity was present in granules isolated from cells challenged with opsonized zymosan, even at 0.05 mM NADPH, and was higher than the activity found in granule fractions from resting cells at all levels of NADPH tested. The addition of as little as 0.1 muM NADH to the reaction mixture was found to inhibit granular NADPH oxidase activity, indicating a possible regulatory role for NADH. These results suggest that NADPH oxidase may be the enzyme that initiates the metabolic events accompanying phagocytosis.
Genotypic comparison of clinical Legionella isolates and patient-related environmental isolates in The Netherlands, 2002–2006
Authors: J.W. Den Boer, J.P. Bruin, L.P.B. Verhoef, K. Van der Zwaluw, R. Jansen, E.P.F. Yzerman
Journal: Clinical Microbiology and Infection (2008)
Neuroanatomy of Memory
Authors: S Zola-Morgan, L R Squire
Journal: Annual Review of Neuroscience (1993)

Three important developments have occurred in the area of  during the past decade. The first was the recognition that there is more than one kind of  (Cohen 1984; Schacter 1987; Squire 1982; Tulving 1985). Declarative  (or, explicit memory) affords the capacity for con­ scious recollections about facts and events. This is the kind of  that is usually referred to when the terms memory or remembering are used in ordinary language. Declarative  can be contrasted with nondeclarative (or implicit) memory, a heterogeneous collection of nonconscious abilities that includes the learning of skills and habits, prim­ ing, and some forms of classical conditioning. In these cases, experience cumulates in behavioral change, but without affording access to any  content. The distinction between declarative and nondeclarative  is fundamental, because it has turned out that different kinds of  are supported by different brain systems. The second important development was the establishment of an animal model of human amnesia in the monkey (Mahut & Moss 1984; Mishkin 1982; Squire & Zola-Morgan 1983). In the 1950s, Scoville & Milner (1957) described the severe amnesia that followed bilateral surgical removal of the medial temporal lobe (patient H.M.). This important case demon­ strated that  is a distinct cerebral function, dissociable from other perceptual and cognitive abilities. Subsequently, surgical lesions of the medial temporai iobe in monkeys, which approximated the damage sus­ tained by patient H.M., were shown to reproduce many features of human  impairment . In particular, both monkeys and humans were
Evaluation of a near-senescent human dermal fibroblast cell line and effect of amelogenin
Authors: S. Almqvist, M. Werthén, A. Johansson, J. Törnqvist, M.S. Ågren, P. Thomsen
Journal: British Journal of Dermatology (2009)

Fibroblast senescence may delay healing of chronic wounds.To characterize a chronic human dermal fibroblast cell line (CRL-7815) with near-senescent properties, cell proliferation and production of wound-healing modulating cytokines, and biosynthesis and remodelling of collagen were compared with normal human dermal fibroblasts. Also, the response of CRL-7815 fibroblasts to the extracellular matrix protein amelogenin that is beneficial in the treatment of stalled chronic wounds was studied.Fibroblast proliferation was monitored by time-resolved growth curves and factors secreted into the culture medium containing 10% fetal bovine serum were measured by enzyme-linked immunosorbent assays. Fibroblast-mediated reorganization was examined in three-dimensional type I collagen matrices.Cell proliferation over 9 days was significantly (P < 0.01) slower for CRL-7815 than for normal fibroblasts. Amelogenin at 1 mg mL(-1) increased (P < 0.01) CRL-7815 proliferation to the level of the normal fibroblasts. The neutrophil chemoattractant interleukin (IL)-8 was low while the constitutive production of monocyte chemoattractant protein (MCP)-1 was highly elevated in medium from cultured CRL-7815 fibroblasts. Amelogenin augmented IL-8 but attenuated MCP-1 secretion in CRL-7815 fibroblasts. The elevated vascular endothelial growth factor production in CRL-7815 fibroblasts was further increased with amelogenin while increased type I collagen synthesis by CRL-7815 was reduced with 0.1 mg mL(-1) amelogenin. The dramatically impaired collagen matrix remodelling with CRL-7815 fibroblasts (P < 0.001) was slightly improved with amelogenin (P = 0.0011).The near-senescent cell line CRL-7815 shares functional anomalies with fibroblasts isolated from nonhealing chronic cutaneous wounds. Amelogenin has the capacity to switch chronic fibroblasts into an acute-like phenotype.