tbuckley/cabot-search huggingface dataset:
Meta-Analysis of Wine and Beer Consumption in Relation to Vascular Risk
Authors: Augusto Di Castelnuovo, Serenella Rotondo, Licia Iacoviello, Maria Benedetta Donati, Giovanni de Gaetano
Journal: Circulation (2002)

Background — Many epidemiological studies have evaluated whether different alcoholic beverages protect against cardiovascular disease. We performed a meta-analysis of 26 studies on the relationship between wine or beer consumption and vascular risk. Methods and Results — General variance-based method and fitting models were applied to pooled data derived from 26 studies that gave a quantitative estimation of the vascular risk associated with either beverage consumption. From 13 studies involving 209 418 persons, the relative risk of vascular disease associated with wine intake was 0.68 (95% confidence interval, 0.59 to 0.77) relative to nondrinkers. There was strong evidence from 10 studies involving 176 042 persons to support a J-shaped relationship between different amounts of wine intake and vascular risk. A statistically significant inverse association was found up to a daily intake of 150 mL of wine. The overall relative risk of moderate beer consumption, which was measured in 15 studies involving 208 036 persons, was 0.78 (95% confidence interval, 0.70 to 0.86). However, no significant relationship between different amounts of beer intake and vascular risk was found after meta-analyzing 7 studies involving 136 382 persons. Conclusions — These findings show evidence of a significant inverse association between light-to-moderate wine consumption and vascular risk. A similar, although smaller association was also apparent in beer consumption studies. The latter finding, however, is difficult to interpret because no meaningful relationship could be found between different amounts of beer intake and vascular risk.
Physical activity and physical activity cognitions are potential factors maintaining fatigue in patients with primary Sjögren's syndrome
Authors: Eveline JM Wouters, Ninke van Leeuwen, Ercolie R Bossema, Aike A Kruize, Hendrika Bootsma, Johannes WJ Bijlsma, Rinie Geenen
Journal: Annals of the Rheumatic Diseases (2011)

Fatigue is a prevalent and debilitating problem in Sjögren's syndrome. It has been suggested that physical activity and cognitions about physical activity can influence fatigue.The aim of this study was to examine fatigue and physical activity levels in patients with Sjögren's syndrome and the associations of physical activity and physical activity cognitions with fatigue.In 300 patients with primary Sjögren's syndrome and 100 demographically matched people from the general population (mean age 57 years, 93% female), fatigue (five dimensions of the multidimensional fatigue inventory) and physical activity (three dimensions of the international physical activity questionnaire) were assessed. The physical activity cognitions 'activity avoidance' and 'somatic focus' of the Tampa scale of kinesiophobia were assessed in the Sjögren's group only.Sjögren's patients had higher scores on all five fatigue dimensions (p<0.001) and lower scores on moderate and vigorous intensity activity (p≤0.001) compared with control participants. In the Sjögren's group, lower physical activity and higher activity avoidance and somatic focus were associated with more severe fatigue on most fatigue dimensions. For general fatigue and physical fatigue, especially the combination of low physical activity and high activity avoidance was associated with more severe fatigue (p<0.05).The results suggest that fatigue in patients with Sjögren's syndrome might be reduced by targeting both physical activity and physical activity cognitions. This suggestion requires verification in clinical experimental studies.
Comment on a prospective evaluation of computerized tomographic (CT) scanning as a screening modality for esophageal varices
Authors: Giancarlo Spinzi, Natalia Terreni, Giovanna Mandelli, Silvia Paggi
Journal: Hepatology (2008)

We read with interest the article by Perri et al. published in a recent issue of HEPATOLOGY.1 Perri et al. report that abdominal computed tomography (CT) performed as the initial screening test for esophageal varices could be cost-effective. The total effective radiation dose for CT was 15 mSv, slightly highly than that for an abdominal and pelvic CT scan. We know that the effective dose, expressed in sieverts, allows for a rough comparison between different CT scenarios but provides only an approximation of the true risk. According to a report by the U.S. National Academy of Sciences, a single population dose of 10 mSv is associated with a lifetime risk of a solid cancer or leukemia of 1 in 2000.2 The radiation dose is particularly problematic when patients have multiple CT scans, as requested if no varices are identified by CT scan, because screening for varices should then be repeated in 2–3 years according to current recommendations. Although the individual estimates are small, the concern about the risks from CT is related to the rapid increase in its use, and it has been estimated that about 1.5%–2.0% of all cancers in the United States may be attributable to radiation from CT studies.3 No large-scale epidemiologic studies of the cancer risks associated with CT scans have been reported, but one such study is just beginning.4 The most effective way to reduce the population dose from CT is simply to decrease the number of CT studies that are prescribed, especially if we have a simple and effective method such as gastroscopy. Perri et al. should at least acknowledge these concerns. Giancarlo Spinzi*, Natalia Terreni*, Giovanna Mandelli*, Silvia Paggi*, * Department of Gastroenterology, Valduce Hospital, Como, Italy.
Genome-wide Interrogation of Germline Genetic Variation Associated With Treatment Response in Childhood Acute Lymphoblastic Leukemia
Authors: Jun J. Yang, Cheng Cheng, Wenjian Yang, Deqing Pei, Xueyuan Cao, Yiping Fan, Stanley B. Pounds, Geoffrey Neale, Lisa R. Treviño, Deborah French, Dario Campana, James R. Downing, William E. Evans, Ching-Hon Pui, Meenakshi Devidas, W. P. Bowman, Bruce M. Camitta, Cheryl L. Willman, Stella M. Davies, Michael J. Borowitz, William L. Carroll, Stephen P. Hunger, Mary V. Relling
Journal: JAMA (2009)

Pediatric acute lymphoblastic leukemia (ALL) is the prototype for a drug-responsive malignancy. Although cure rates exceed 80%, considerable unexplained interindividual variability exists in treatment response.To assess the contribution of inherited genetic variation to therapy response and to identify germline single-nucleotide polymorphisms (SNPs) associated with risk of minimal residual disease (MRD) after remission induction chemotherapy.Genome-wide interrogation of 476,796 germline SNPs to identify genotypes that were associated with MRD in 2 independent cohorts of children with newly diagnosed ALL: 318 patients in St Jude Total Therapy protocols XIIIB and XV and 169 patients in Children's Oncology Group trial P9906. Patients were enrolled between 1994 and 2006 and last follow-up was in 2006.Minimal residual disease at the end of induction therapy, measured by flow cytometry.There were 102 SNPs associated with MRD in both cohorts (median odds ratio, 2.18; P < or = .0125), including 5 SNPs in the interleukin 15 (IL15) gene. Of these 102 SNPs, 21 were also associated with hematologic relapse (P < .05). Of 102 SNPs, 21 were also associated with antileukemic drug disposition, generally linking MRD eradication with greater drug exposure. In total, 63 of 102 SNPs were associated with early response, relapse, or drug disposition.Host genetic variations are associated with treatment response for childhood ALL, with polymorphisms related to leukemia cell biology and host drug disposition associated with lower risk of residual disease.
Four-Month Moxifloxacin-Based Regimens for Drug-Sensitive Tuberculosis
Authors: Stephen H. Gillespie, Angela M. Crook, Timothy D. McHugh, Carl M. Mendel, Sarah K. Meredith, Stephen R. Murray, Frances Pappas, Patrick P.J. Phillips, Andrew J. Nunn
Journal: New England Journal of Medicine (2014)

Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis.
Plasma Fibronectin Promotes Lung Metastasis by Contributions to Fibrin Clots and Tumor Cell Invasion
Authors: Gunjan Malik, Lynn M. Knowles, Rajiv Dhir, Shuping Xu, Shuting Yang, Erkki Ruoslahti, Jan Pilch
Journal: Cancer Research (2010)

Abstract The attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack plasma fibronectin. This multifunctional adhesive glycoprotein becomes cross-linked to fibrin during clotting. Here, we report that eliminating plasma fibronectin from the blood circulation reverses the prometastatic effects of blood clotting and tumor cell integrin αvβ3. In vitro studies showed that fibrin-fibronectin complexes, but not purified fibrin, supported tumor cell attachment and invasion. These functions correlate with the ability of fibrin-fibronectin complexes to induce the activation of integrin αvβ3. Our findings reveal an important contribution of plasma fibronectin in lung metastasis. Furthermore, they suggest that the previously noted effects of blood clotting on lung metastasis might be mediated in part by a fibronectin-αvβ3 integrin axis, in which plasma fibronectin has to be incorporated into the blood clot. Cancer Res; 70(11); 4327–34. ©2010 AACR.
Ca <sup>2+</sup> Signaling in Cardiac Myocytes Overexpressing the α <sub>1</sub> Subunit of L-Type Ca <sup>2+</sup> Channel
Authors: Long-Sheng Song, António Guia, James N. Muth, Marta Rubio, Shi-Qiang Wang, Rui-Ping Xiao, Ira R. Josephson, Edward G. Lakatta, Arnold Schwartz, Heping Cheng
Journal: Circulation Research (2002)

Voltage-gated L-type Ca(2+) channels (LCCs) provide Ca(2+) ingress into cardiac myocytes and play a key role in intracellular Ca(2+) homeostasis and excitation-contraction coupling. We investigated the effects of a constitutive increase of LCC density on Ca(2+) signaling in ventricular myocytes from 4-month-old transgenic (Tg) mice overexpressing the alpha(1) subunit of LCC in the heart. At this age, cells were somewhat hypertrophic as reflected by a 20% increase in cell capacitance relative to those from nontransgenic (Ntg) littermates. Whole cell I(Ca) density in Tg myocytes was elevated by 48% at 0 mV compared with the Ntg group. Single-channel analysis detected an increase in LCC density with similar conductance and gating properties. Although the overexpressed LCCs triggered an augmented SR Ca(2+) release, the "gain" function of EC coupling was uncompromised, and SR Ca(2+) content, diastolic cytosolic Ca(2+), and unitary properties of Ca(2+) sparks were unchanged. Importantly, the enhanced I(Ca) entry and SR Ca(2+) release were associated with an upregulation of the Na(+)-Ca(2+) exchange activity (indexed by the half decay time of caffeine-elicited Ca(2+) transient) by 27% and SR Ca(2+) recycling by approximately 35%. Western analysis detected a 53% increase in the Na(+)-Ca(2+) exchanger expression but no change in the abundance of ryanodine receptor (RyR), SERCA2, and phospholamban. Analysis of I(Ca) kinetics suggested that SR Ca(2+) release-dependent inactivation of LCCs remains intact in Tg cells. Thus, in spite of the modest cardiac hypertrophy, the overexpressed LCCs form functional coupling with RyRs, preserving both orthograde and retrograde Ca(2+) signaling between LCCs and RyRs. These results also suggest that a modest but sustained increase in Ca(2+) influx triggers a coordinated remodeling of Ca(2+) handling to maintain Ca(2+) homeostasis.
B-lymphocyte Fc receptor-associated non-H-2 antigens are determined by a single polymorphic locus which is linked of the Mls locus
Authors: HB Dickler, A Ahmed, DH Sachs
Journal: The Journal of Experimental Medicine (1977)

Certain non-H-2 alloantigens are associated with murine B-lymphocyte Fc receptors in that pretreatment of spleen cells with alloantibodies against these antigens inhibited binding of Ig complexes to B-cell Fc receptors. This inhibition was specific in that: (a) as has been shown previously, the Fc portion of the alloantibody was not required to produce inhibition; and (b) antibodies against some non-H-2 antigens but not antibodies against others (including some that were expressed on B cells) caused such inhibition. Backcross experiments revealed that the B-cell Fc receptor-associated non-H-2 antigens were determined by the gene(s) of a single background locus in each of the three strains tested (A/J, B10, and CBA/J). This locus was poly-morphic in that at least four different B-cell Fc receptor:associated non-H-2 antigens were identified (one each in the A/J, B10, and CBAJJ and one antigen shared or crossreactive between the B10 and CBA/J). These antigens were primarily but not exclusively expressed on B lymphocytes as determined by immunofluorescence studies, and on the basis of capping experiments they did not appear to be identical to B-cell Fc receptors. Linkage studies revealed that the locus which determined these antigens was not linked to the albino locus nor the heavy chain allotype locus and expression was neither sex-limited nor an X-linked recessive trait. However, this locus was closely linked but not identical to the Mls locus (apparent recombination frequency 6.8 percent). Thus, two closely linked non-H-2 loci both determine the expression of antigens which have characteristics similar to Ia antigens. One locus is polymorphic and determines the expression of antigens which are primarily expressed on B cells and are specifically associated with the Fc receptors of these cells. The other (Mls locus) determines antigens which are stimulatory in mixed lymphocyte cultures. These observations suggest that there may be a second gene complex which is the analogue of the I region of the H-2 complex.
Phase II clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neoadjuvant treatment in stages II and IIIA HER2-overexpressing breast cancer patients. GEICAM 2003-03 study
Authors: A Antón, A Ruiz, A Plazaola, L Calvo, M A Seguí, A Santaballa, M Muñoz, P Sánchez, A Miguel, E Carrasco, J Lao, J Camps, J Alfaro, S Antolín, M C Cámara
Journal: Annals of Oncology (2010)
AMG 102, A Fully Human Anti-Hepatocyte Growth Factor/Scatter Factor Neutralizing Antibody, Enhances the Efficacy of Temozolomide or Docetaxel in U-87 MG Cells and Xenografts
Authors: H. Toni Jun, Jan Sun, Karen Rex, Robert Radinsky, Richard Kendall, Angela Coxon, Teresa L. Burgess
Journal: Clinical Cancer Research (2007)

Hepatocyte growth factor (HGF/SF) and its receptor c-Met have previously been shown to be up-regulated in multiple human cancers, including glioblastoma multiforme. To better understand if AMG 102, a fully human, anti-HGF/SF-neutralizing antibody, could be incorporated into current clinical practice, AMG 102 was tested preclinically in combination with temozolomide or docetaxel to determine if enhanced efficacy was observed compared with AMG 102 alone.The effects of AMG 102 were tested for antiproliferative activity in combination with temozolomide or docetaxel on U-87 MG cells in vitro and for antitumor activity in a U-87 MG xenograft model in vivo. Apoptotic activity was also measured for AMG 102 and docetaxel combined in vitro.Treatment with temozolomide combined with AMG 102 resulted in increased inhibition of cell growth in vitro compared with treatment with either single agent alone. In U-87 MG xenografts in vivo, AMG 102 combined with temozolomide or docetaxel significantly increased the inhibitory effect on tumor growth when compared with treatment with either agent alone (P < 0.0001 and P < 0.015, respectively). In vitro, docetaxel alone induced both caspase-3/7 activity as well as poly(ADP)ribose polymerase and caspase-7 cleavage in U-87 MG cells; these events were enhanced when used in combination with AMG 102. Importantly, there was no evidence of interference between AMG 102 and either temozolomide or docetaxel in vitro or in vivo.These studies support testing of AMG 102 in combination with temozolomide or docetaxel. Such combinations may represent promising, novel clinical therapeutic strategies for cancers that are dependent on the HGF/SF/SF:c-Met pathway in the oncology setting.
From the Museum: the Art of Thinking. Part Three: Reason
Authors: Tom Kotsimbos
Journal: European Respiratory Journal (2014)

Witches in Flight is a thinly veiled allegory with striking imagery in which myth and reality are intimately intertwined with the absence and presence of reason, respectively. A floating formation of three dunces-hat wearing warlocks actively torments a naked man in mid-air as he is carried away. The warlocks and their catch are suspended in an airless space framed by pure blackness and seemingly emit their own light (shadowless). Directly below, a fully dressed man is "caught" in their light as he desperately tries to flee over a barren landscape. He is warding off unseen evil as he hides under a white sheet. In the darkness on either side are a "fallen" figure, face downwards and covering his ears; and an "ignorant" donkey looking on unfazed, eyes wide open and ears pricked. The form, content and symbolism of this painting all suggest "evil spiralling out of control" as "reason goes to sleep" in a relatively modern way. Suddenly, the triumphs of the enlightenment and rationality have fuelled the expression of the irrational and a "dark romanticism" that act as counterpoints
The Neuropathy of Sjögren's Syndrome
Authors: H. BENFER KALTREIDER
Journal: Annals of Internal Medicine (1969)

Ten patients had Sjögren's syndrome and peripheral or trigeminal neuropathy, or both. The neurologic features of other connective tissue diseases are reviewed for comparison. The peripheral neuropathy in Sjögren's syndrome was predominately sensory and characteristically mild, distal, and symmetrical. Spinal fluid examinations were usually normal. The neuropathy in Sjögren's syndrome was indistinguishable from that seen in rheumatoid arthritis. Initiation or manipulation of corticoid dosage was not related to the onset of neuropathy. The therapeutic response to steroids was unpredictable. A sensory trigeminal neuropathy occurred in four patients. It was characterized by numbness, hypesthesia, and tingling paresthesias. The divisional distribution of sensory deficit favored a peripheral rather than a central lesion or an entrapment neuropathy. The presence of neuropathy correlated strongly with vasculitis in the nerves and muscle. The vascular inflammation was felt to be causally related to the pathogenesis of the neuropathy.
Characterization of Gene Amplification–Driven SKP2 Overexpression in Myxofibrosarcoma: Potential Implications in Tumor Progression and Therapeutics
Authors: Chien-Feng Li, Ju-Ming Wang, Hong-Yo Kang, Chiung-Kuei Huang, Jun-Wen Wang, Fu-Min Fang, Yu-Hui Wang, Wen-Ren Wu, Shau-Hsuan Li, Shih-Chen Yu, Jen-Chieh Lee, Jui Lan, Yow-Ling Shiue, Li-Ching Wu, Hsuan-Ying Huang
Journal: Clinical Cancer Research (2012)

Myxofibrosarcoma remains obscure in molecular determinants of clinical aggressiveness, for which we elucidated implications of SKP2 amplification.Array comparative genomic hybridization was applied on samples and cell lines (NMFH-1 to OH931) to search causal genes of tumor progression. SKP2 gene dosage was determined in 82 independent tumors for clinical correlates. Stable SKP2 knockdown was achieved in myxofibrosarcoma cells to assess its oncogenic attributes and candidate mediators in prometastatic function. Pharmacologic assays were evaluated in vitro and in vivo for the therapeutic relevance of bortezomib.DNA gains frequently involved 5p in which three amplicons were differentially overrepresented in samples behaving unfavorably, encompassing mRNA-upregulated TRIO, SKP2, and AMACR genes. Detected in NMFH-1 cells and 38% of tumors, SKP2 amplification was associated with SKP2 immunoexpression and adverse prognosticators and independently predictive of worse outcomes. Nevertheless, SKP2-expressing OH931 cells and 14% of such tumors lacked gene amplification. Knockdown of SKP2 suppressed proliferation, anchorage-independent growth, migration, and invasion of sarcoma cells and downregulated motility-promoting genes, including ITGB2, ACTN1, IGF1, and ENAH. In vitro, bortezomib downregulated SKP2 expression at the mRNA level with p27(kip1) accumulation, induced caspase activation, and decreased cell viability in myxofibrosarcoma cells but not in fibroblasts. In vivo, bortezomib inhibited growth of NMFH-1 xenografts, the cells of which displayed decreased SKP2 expression but increased p27(kip1) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL).As a predominant mechanism driving protein overexpression, SKP2 amplification confers tumor aggressiveness in myxofibrosarcoma. The sensitivity of myxofibrosarcoma cells to bortezomib with SKP2-repressing effect indicates the potentiality of ubiquitin-proteasome pathway as a therapeutic target.
Sensitization of Tumor-Associated Endothelial Cell Apoptosis by the Novel Vascular-Targeting Agent ZD6126 in Combination with Cisplatin
Authors: Hisatsugu Goto, Seiji Yano, Yuka Matsumori, Hirohisa Ogawa, David C. Blakey, Saburo Sone
Journal: Clinical Cancer Research (2004)

Abstract Purpose: ZD6126 is a novel vascular-targeting agent that selectively disrupts the tubulin cytoskeleton of endothelial cells. In the immature vessels characteristic of tumor vasculature, this leads to endothelial cell contraction, blood vessel congestion, and, consequently, tumor cell death. ZD6126 has been shown to delay tumor growth in a range of xenograft models. The antitumor effect of ZD6126 can be increased in combination with cisplatin or radiation therapy, although the precise mechanism of this enhancement has not been demonstrated. ZD6126 treatment has also been shown to inhibit lung metastasis, and the present study has explored the potential to increase the antimetastatic effect of ZD6126 by combining with cisplatin, and the underlining mechanism has been investigated. Experimental Design: Human lung adenocarcinoma PC14PE6 cells were injected into the tail vein of nude mice. Five weeks after injection animals were treated with ZD6126 (200 mg/kg i.p.), cisplatin (6 mg/kg i.v.), or a combination of the two agents. The animals were sacrificed 24 hours later, and the extent of lung metastases and the presence of apoptotic cells were assessed. Results: Histologic analysis revealed that the ZD6126/cisplatin combination resulted in a 2 to 4-fold increase in the total number of tumor-associated apoptotic cells compared with either treatment alone. ZD6126 alone induced apoptosis of tumor-associated endothelial cells in tumors, and the extent of apoptosis was increased 2-fold in combination with cisplatin. The lung weight was significantly reduced, and the number of metastatic nodules significantly was lower in the combined treatment group than in the control group. Conclusions: These data suggest that the antimetastatic effect of the vascular-targeting agent ZD6126 can be increased by use in combination with cisplatin, which increases the incidence of endothelial cell apoptosis.
Platelet Serotonin Release in Penicillin Allergy
Authors: Stanley Comaish
Journal: British Journal of Dermatology (1968)

Journal Article Platelet Serotonin Release in Penicillin Allergy Get access Stanley Comaish Stanley Comaish Department of Dermatology, University of Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 11, 1 November 1968, Pages 765–766, https://doi.org/10.1111/j.1365-2133.1968.tb11944.x Published: 01 November 1968