tbuckley/cabot-search huggingface dataset:
Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema
Authors: Gad Cotter, Einat Metzkor, Edo Kaluski, Zwi Faigenberg, Rami Miller, Avi Simovitz, Ori Shaham, Doron Marghitay, Maya Koren, Alex Blatt, Yaron Moshkovitz, Ronit Zaidenstein, Ahuva Golik
Journal: The Lancet (1998)
The Anti-Mullerian hormone and ovarian cancer
Authors: Antonio La Marca, Annibale Volpe
Journal: Human Reproduction Update (2007)

The Anti-Mullerian hormone (AMH), which is produced by fetal Sertoli cells, is responsible for regression of Mullerian ducts, the anlagen for uterus and Fallopian tubes, during male sex differentiation. Ovarian granulosa cells also secrete AMH from late in fetal life. The patterns of expression of AMH and its type II receptor in the post-natal ovary indicate that AMH may play an important role in ovarian folliculogenesis. Recent advances in the physiological role of AMH has stimulated interest in the significance of AMH as a diagnostic marker and therapeutic agent for ovarian cancer. Currently, AMH has been shown to be a circulating marker specifically for granulosa cell tumour (GCT). Its diagnostic performance seems to be very good, with a sensitivity ranging between 76 and 93%. In patients treated for GCT, AMH may be used post-operatively as marker for the efficacy of surgery and for disease recurrence. Based on the physiological inhibitory role of AMH in the Mullerian ducts, it has been proposed that AMH may inhibit epithelial ovarian cancer cell both in vitro and in vivo . These observations will be the basis for future research aiming to investigate the possible clinical role of AMH as neo-adjuvant, or most probably adjuvant, therapy for ovarian cancer.
Recent Advances in Autism Research as Reflected in DSM-5 Criteria for Autism Spectrum Disorder
Authors: Catherine Lord, Somer L. Bishop
Journal: Annual Review of Clinical Psychology (2015)

This article provides a selective review of advances in scientific knowledge about autism spectrum disorder (ASD), using DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) diagnostic criteria as a framework for the discussion. We review literature that prompted changes to the organization of ASD symptoms and diagnostic subtypes in DSM-IV, and we examine the rationale for new DSM-5 specifiers, modifiers, and severity ratings as well as the introduction of the diagnosis of social (pragmatic) communication disorder. Our goal is to summarize and critically consider the contribution of clinical psychology research, along with that of other disciplines, to the current conceptualization of ASD.
<i>In vivo</i> Tumor Targeting Using a Novel Intestinal Pathogen-Based Delivery Approach
Authors: Klaus-Peter Janssen, Danijela Vignjevic, Raphaël Boisgard, Thomas Falguières, Guilhem Bousquet, Didier Decaudin, Frédéric Dollé, Daniel Louvard, Bertrand Tavitian, Sylvie Robine, Ludger Johannes
Journal: Cancer Research (2006)

Abstract Efficient methods for tumor targeting are eagerly awaited and must satisfy several challenges: molecular specificity, transport through physiologic barriers, and capacity to withstand extracellular or intracellular degradation and inactivation by the immune system. Through interaction with its hosts, the intestinal pathogen-produced Shiga toxin has evolved molecular properties that are of interest in this context. Its nontoxic B-subunit binds to the cellular toxin receptor, glycosphingolipid Gb3, which is highly expressed on human cancers and has recently been reported to be involved in the formation of metastasis in colorectal cancers. Its function as a target for cancer therapy has already been addressed in xenograft experiments. We here show that after oral or i.v. injections in mice, the B-subunit targets spontaneous digestive Gb3-expressing adenocarcinomas. The nontumoral mucosa is devoid of labeling, with the exception of rare enteroendocrine and CD11b-positive cells. As opposed to other delivery tools that are often degraded or recycled on cancer cells, the B-subunit stably associates with these cells due to its trafficking via the retrograde transport route. This can be exploited for the in vivo delivery of contrast agents to tumors, as exemplified using fibered confocal fluorescence endoscopy and positron emission tomography (PET) imaging. In conclusion, the data presented in this manuscript lay the groundwork for a novel delivery technology that, in addition to its use for molecular imaging applications such as noninvasive PET, could also be exploited for targeted tumor therapies. (Cancer Res 2006; 66(14): 7230-6)
Colonic mucosa-associated diffusely adherent<i>afaC+ Escherichia coli</i>expressing<i>lpfA</i>and<i>pks</i>are increased in inflammatory bowel disease and colon cancer
Authors: Maelle Prorok-Hamon, Melissa K Friswell, Abdullah Alswied, Carol L Roberts, Fei Song, Paul K Flanagan, Paul Knight, Caroline Codling, Julian R Marchesi, Craig Winstanley, Neil Hall, Jonathan M Rhodes, Barry J Campbell
Journal: Gut (2013)

<h3>Objective</h3> Colonic mucosa-associated <i>Escherichia coli</i> are increased in Crohn9s disease (CD) and colorectal cancer (CRC). They variously haemagglutinate, invade epithelial cell lines, replicate within macrophages, translocate across M (microfold) cells and damage DNA<i>.</i> We investigated genes responsible for these effects and their co-association in colonic mucosal isolates. <h3>Design</h3> A fosmid library yielding 968 clones was prepared in <i>E coli</i> EPI300-T1 using DNA from a haemagglutinating CRC isolate, and resulting haemagglutinating clones were 454-pyrosequenced. PCR screening was performed on 281 colonic <i>E coli</i> isolates from inflammatory bowel disease (IBD) (35 patients), CRC (21) and controls (24; sporadic polyps or irritable bowel syndrome). <h3>Results</h3> 454-Pyrosequencing of fosmids from the haemagglutinating clones (n=8) identified the afimbrial adhesin <i>afa</i>-<i>1</i> operon. Transfection of <i>afa</i>-<i>1</i> into <i>E coli</i> K-12 predictably conferred diffuse adherence plus invasion of HEp-2 and I-407 epithelial cells, and upregulation of vascular endothelial growth factor. <i>E coli</i> expressing <i>afaC</i> were common in CRC (14/21, p=0.0009) and CD (9/14, p=0.005) but not ulcerative colitis (UC; 8/21) compared with controls (4/24). <i>E coli</i> expressing both <i>afaC</i> and <i>lpfA</i> (relevant to M-cell translocation) were common in CD (8/14, p=0.0019) and CRC (14/21, p=0.0001), but not UC (6/21) compared with controls (2/24). <i>E coli</i> expressing both <i>afaC</i> and <i>pks</i> (genotoxic) were common in CRC (11/21, p=0.0015) and UC (8/21, p=0.022), but not CD (4/14) compared with controls (2/24). All isolates expressed <i>dsbA</i> and <i>htrA</i> relevant to intra-macrophage replication, and 242/281 expressed <i>fimH</i> encoding type-1 fimbrial adhesin. <h3>Conclusions</h3> IBD and CRC commonly have colonic mucosal <i>E coli</i> that express genes that confer properties relevant to pathogenesis including M-cell translocation, angiogenesis and genotoxicity.
Modifiable Risk Factors and Major Cardiac Events Among Adult Survivors of Childhood Cancer
Authors: Gregory T. Armstrong, Kevin C. Oeffinger, Yan Chen, Toana Kawashima, Yutaka Yasui, Wendy Leisenring, Marilyn Stovall, Eric J. Chow, Charles A. Sklar, Daniel A. Mulrooney, Ann C. Mertens, William Border, Jean-Bernard Durand, Leslie L. Robison, Lillian R. Meacham
Journal: Journal of Clinical Oncology (2013)

To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer.Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models.Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all P(trend) < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7).Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.
Circulating myeloid and plasmacytoid dendritic cells after allergen inhalation in asthmatic subjects
Authors: E. Farrell, T. M. O’Connor, M. Duong, R. M. Watson, T. Strinich, G. M. Gauvreau, P. M. O’Byrne
Journal: Allergy (2007)

Background: Dendritic cells are key contributors to initiation and maintenance of T‐cell immunity to inhaled allergen. The purpose of this study was to enumerate the changes in peripheral blood myeloid (mDCs) and plasmacytoid dendritic cells (pDCs), the DCs expressing chemokine receptor 6 (CCR6) and chemokine receptor 7 (CCR7), following diluent and allergen inhalation in asthmatic subjects. Methods: Peripheral blood was obtained from 16 allergic asthmatic subjects before and at 0.5, 1, 2, 3, 4, 6, 24, and 48 h after inhaled diluent and allergen challenges. Dendritic cells were enumerated using flow cytometry. Results: Allergen inhalation significantly reduced mDCs at 6 h (21.3 ± 2.0 vs 15.0 ± 1.8/μl blood; P &lt; 0.05) and 24 h (21.5 ± 3.4 vs 16.4 ± 2.4/μl blood; P &lt; 0.05) after challenge. Circulating pDCs were significantly lower than baseline up to 24 h after both allergen and diluent challenges. There was a significant efflux of CCR6 + mDCs from peripheral blood at 6 h and CCR6 + pDCs at 4 h after allergen challenge, when compared with diluent. There was no difference in the number of circulating CCR7 + mDCs or pDCs after diluent or allergen challenges. Conclusions: Peripheral blood mDCs and CCR6 + mDCs, but not pDCs, are reduced up to 24 h after allergen inhalation. Thus, allergen inhalation causes trafficking of immature CCR6 + DCs from blood into the airway, while that of the trafficking of the mature CCR7 + DCs from the airways into the regional lymph nodes probably occurs through the lymphatic system.
Clusterin Isoforms Differentially Affect Growth and Motility of Prostate Cells: Possible Implications in Prostate Tumorigenesis
Authors: Roberta M. Moretti, Marina Montagnani Marelli, Stefania Mai, Anna Cariboni, Maurizio Scaltriti, Saverio Bettuzzi, Patrizia Limonta
Journal: Cancer Research (2007)

Abstract Besides a fully processed, secreted form of clusterin (sCLU), an alternative proapoptotic form of the protein targeting the nucleus (nCLU) was recently described. The possible differential roles played by the two clusterin forms in growth and motility of nonmalignant and malignant prostate cells are investigated here. sCLU or nCLU was transiently transfected in both androgen-independent prostate cancer cells (PC3 and DU 145) and immortalized prostate epithelial cells (PNT1A, a nontumoral control). Then, cell growth, motility, and cytoskeleton organization were studied. We found that (a) in PNT1A cells, both sCLU and nCLU significantly decreased cell proliferation and motility; (b) in PC3 and DU 145 cancer cells, only nCLU inhibited cell growth and migration, with sCLU being ineffective; and (c) the antimotility effect of nCLU was accompanied by a dramatic dismantling of the actin cytoskeleton. Moreover, transfection with “full-length” CLU cDNA produced both sCLU and nCLU in nonmalignant PNT1A cells, whereas only sCLU was found in cancer cells. Thus, CLU gene expression might play a crucial role in prostate tumorigenesis by exerting differential biological effects on normal versus tumor cells through differential processing of CLU isoforms in the two cell systems. We also found that nCLU binds to α-actinin, a key protein for the regulation of actin cytoskeleton, and that nCLU and α-actinin colocalize in the cytoplasm. Thus, the antimotility activity of nCLU and its ability to cause dismantling of the actin cytoskeleton seem to be mediated by its binding to α-actinin. [Cancer Res 2007;67(21):10325–33]
Magnitude and Variability of the Glucagon-Like Peptide-1 Response in Patients With Type 2 Diabetes up to 2 Years Following Gastric Bypass Surgery
Authors: Bart J. Van der Schueren, Peter Homel, Mariam Alam, Keesandra Agenor, Gary Wang, David Reilly, Blandine Laferrère
Journal: Diabetes Care (2011)

To characterize the magnitude and variance of the change of glucose and glucagon-like peptide-1 (GLP-1) concentrations, and to identify determinants of glucose control up to 2 years after gastric bypass (GBP).Glucose and GLP-1 concentrations were measured during an oral glucose challenge before and 1, 12, and 24 months after GBP in 15 severely obese patients with type 2 diabetes.Glucose area under the curve from 0 to 180 min (AUC(0-180)) started decreasing in magnitude (P < 0.05) 1 month after surgery. GLP-1 AUC(0-180) increased in magnitude 1 month after GBP (P < 0.05), with increased variance only after 1 year (P(σ)(2) ≤ 0.001). GLP-1 AUC(0-180) was positively associated with insulin AUC(0-180) (P = 0.025).The increase in variance of GLP-1 at 1 and 2 years after GBP suggests mechanisms other than proximal gut bypass to explain the enhancement of GLP-1 secretion. The association between GLP-1 and insulin concentrations supports the idea that the incretins are involved in glucose control after GBP.
Molecular Staging for Survival Prediction of Colorectal Cancer Patients
Authors: Steven Eschrich, Ivana Yang, Greg Bloom, Ka Yin Kwong, David Boulware, Alan Cantor, Domenico Coppola, Mogens Kruhøffer, Lauri Aaltonen, Torben F. Orntoft, John Quackenbush, Timothy J. Yeatman
Journal: Journal of Clinical Oncology (2005)

Purpose The Dukes' staging system is the gold standard for predicting colorectal cancer prognosis; however, accurate classification of intermediate-stage cases is problematic. We hypothesized that molecular fingerprints could provide more accurate staging and potentially assist in directing adjuvant therapy. Methods A 32,000 cDNA microarray was used to evaluate 78 human colon cancer specimens, and these results were correlated with survival. Molecular classifiers were produced to predict outcome. Results Molecular staging, based on 43 core genes, was 90% accurate (93% sensitivity, 84% specificity) in predicting 36-month overall survival in 78 patients. This result was significantly better than Dukes' staging (P = .03878), discriminated patients into significantly different groups by survival time (P &lt; .001, log-rank test), and was significantly different from chance (P &lt; .001, 1,000 permutations). Furthermore, the classifier was able to discriminate a survival difference in an independent test set from Denmark. Molecular staging identifies patient prognosis (as represented by 36-month survival) more accurately than the traditional clinical staging, particularly for intermediate Dukes' stage B and C patients. The classifier was based on a core set of 43 genes, including osteopontin and neuregulin, which have biologic significance for this disease. Conclusion These data support further evaluation of molecular staging to discriminate good from poor prognosis patients, with the potential to direct adjuvant therapy.
The relationship between maternal adiposity and infant weight gain, and childhood wheeze and atopy
Authors: Katharine C Pike, Hazel M Inskip, Sian M Robinson, Cyrus Cooper, Keith M Godfrey, Graham Roberts, Jane S A Lucas
Journal: Thorax (2013)

<h3>Background</h3> Obesity and asthma have increased in westernised countries. Maternal obesity may increase childhood asthma risk. If this relation is causal, it may be mediated through factors associated with maternal adiposity, such as fetal development, pregnancy complications or infant adiposity. We investigated the relationships of maternal body mass index (BMI) and fat mass with childhood wheeze, and examined the influences of infant weight gain and childhood obesity. <h3>Methods</h3> Maternal prepregnancy BMI and estimated fat mass (from skinfold thicknesses) were related to asthma, wheeze and atopy in 940 children. Transient or persistent/late wheeze was classified using questionnaire data collected at ages 6, 12, 24 and 36 months and 6 years. At 6 years, skin-prick testing was conducted and exhaled nitric oxide and spirometry measured. Infant adiposity gain was calculated from skinfold thickness at birth and 6 months. <h3>Results</h3> Greater maternal BMI and fat mass were associated with increased childhood wheeze (relative risk (RR) 1.08 per 5 kg/m<sup>2</sup>, p=0.006; RR 1.09 per 10 kg, p=0.003); these reflected associations with transient wheeze (RR 1.11, p=0.003; RR 1.13, p=0.002, respectively), but not with persistent wheeze or asthma. Infant adiposity gain was associated with persistent wheeze, but not significantly. Adjusting for infant adiposity gain or BMI at 3 or 6 years did not reduce the association between maternal adiposity and transient wheeze. Maternal adiposity was not associated with offspring atopy, exhaled nitric oxide, or spirometry. <h3>Discussion</h3> Greater maternal adiposity is associated with transient wheeze but not asthma or atopy, suggesting effects upon airway structure/function but not allergic predisposition.
Statin Use, Clinical Fracture, and Bone Density in Postmenopausal Women: Results from the Women's Health Initiative Observational Study
Authors: Andrea Z. LaCroix
Journal: Annals of Internal Medicine (2003)

Background: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to stimulate bone formation in laboratory studies, both in vitro and in vivo. While early epidemiologic studies showed lower risk for hip fracture among statin users than nonusers, subsequent studies have produced mixed results. Objective: To examine the association of statin use with incidence of hip, lower arm or wrist, and other clinical fractures and with baseline levels of bone density. Design: Prospective study. Setting: Women's Health Initiative Observational Study conducted in 40 clinical centers in the United States. Participants: 93 716 postmenopausal women ages 50 to 79 years. Measurements: Rates of hip, lower arm or wrist, and other clinical fractures were compared among 7846 statin users and 85 870 nonusers over a median follow-up of 3.9 years. In 6442 women enrolled at three clinical centers, baseline levels of total hip, posterioranterior spine, and total-body bone density measured by using dual-energy x-ray absorptiometry were compared according to statin use. Results: Age-adjusted rates of hip, lower arm or wrist, and other clinical fractures were similar between statin users and nonusers regardless of duration of statin use. The multivariate-adjusted hazard ratios for current statin use were 1.22 (95% CI, 0.83 to 1.81) for hip fracture, 1.04 (CI, 0.85 to 1.27) for lower arm or wrist fracture, and 1.11 (CI, 1.00 to 1.22) for other clinical fracture. Bone density levels did not statistically differ between statin users and nonusers at any skeletal site after adjustment for age, ethnicity, body mass index, and other factors. Conclusion: Statin use did not improve fracture risk or bone density in the Women's Health Initiative Observational Study. The cumulative evidence does not warrant use of statins to prevent or treat osteoporosis.
Mitogen-reactive B cell subpopulations selectively express different sets of V regions.
Authors: D Primi, F Mami, C Le Guern, P A Cazenave
Journal: The Journal of Experimental Medicine (1982)

The experiments presented here were designed to investigate whether the idiotypic repertoire is equally distributed among B cells subpopulations as defined by mitogen reactivity. To this end we used lipopolysaccharides (LPS) and Nocardia delipidated cell mitogens (NDCM), which are two mitogens that have been described to act on different B cell subsets. The repertoire can be defined in quantitative terms as the frequency of B cells that are precursors for clones secreting immunoglobulin with a given specificity or with a determinate idiotype. We determined, therefore, the absolute frequency of LPS- and NDCM-sensitive B lymphocytes secreting immunoglobulin molecules that bear three idiotopes originally found on a monoclonal anti-beta galactosidase antibody. Because the frequencies of B cells carrying one of these idiotypes are dramatically different in the LPS- and NDCM-sensitive B cells subsets, we conclude that the idiotypic repertoire is not randomly distributed among mitogen-reactive B cell subpopulations.
A population-based assessment of live births in women with systemic lupus erythematosus
Authors: Évelyne Vinet, Jeremy Labrecque, Christian A Pineau, Ann E Clarke, Yvan St-Pierre, Robert Platt, Sasha Bernatsky
Journal: Annals of the Rheumatic Diseases (2011)

The authors aim to calculate the number of live births, before and after systemic lupus erythematosus (SLE) diagnosis, in women diagnosed during their reproductive years and to compare this with general population rates.The authors identified women with SLE using Quebec administrative databases (1 January 1994 to 31 December 2003). The authors determined the number of live births, and calculated the standardised incidence ratio (SIR) of observed to expected live births.1334 women with SLE were identified. Overall, the number of live births over the interval (559) was below that which would be expected (708) (SIR 0.79; 95% CI 0.73 to 0.86). Compared with the general population, live births were substantially lower after SLE diagnosis (SIR 0.62; 95% CI 0.55 to 0.70) than before diagnosis (SIR 1.01; 95% CI 0.90 to 1.13).After diagnosis, women with SLE have substantially fewer live births than the general population.
‘Particle genetics’: treating every cell as unique
Authors: Gaël Yvert
Journal: Trends in Genetics (2013)

Genotype-phenotype relations are usually inferred from a deterministic point of view. For example, quantitative trait loci (QTL), which describe regions of the genome associated with a particular phenotype, are based on a mean trait difference between genotype categories. However, living systems comprise huge numbers of cells (the 'particles' of biology). Each cell can exhibit substantial phenotypic individuality, which can have dramatic consequences at the organismal level. Now, with technology capable of interrogating individual cells, it is time to consider how genotypes shape the probability laws of single cell traits. The possibility of mapping single cell probabilistic trait loci (PTL), which link genomic regions to probabilities of cellular traits, is a promising step in this direction. This approach requires thinking about phenotypes in probabilistic terms, a concept that statistical physicists have been applying to particles for a century. Here, I describe PTL and discuss their potential to enlarge our understanding of genotype-phenotype relations.