tbuckley/cabot-search huggingface dataset:
Increased activation of lymphocytes infiltrating primary colorectal cancers following immunisation with the anti-idiotypic monoclonal antibody 105AD7
Authors: C A Maxwell-Armstrong, L G Durrant, R A Robins, A M Galvin, J H Scholefield, J D Hardcastle
Journal: Gut (1999)

<h3>BACKGROUND</h3> The anti-idiotypic monoclonal antibody 105AD7 mimics the tumour associated antigen 791Tgp72, expressed on 70–80% of colorectal cancers. Phase I studies have shown that the vaccine is non-toxic, and a number of patients have been immunised prior to resection of their primary tumours. <h3>AIMS</h3> To assess lymphocyte activation at the tumour site by measuring expression of the α subunit of the interleukin 2 receptor (CD25). <h3>METHODS</h3> Nineteen patients with primary colorectal cancer were immunised with varying doses of 105AD7 prior to resection of their primary tumours. Samples of normal bowel and tumour edge/centre from 16 patients were available for immunohistochemical staining with a monoclonal antibody against CD25. Samples from a matched control group were also stained. Fresh tumours from 14 immunised patients and 31 unimmunised control patients were disaggregated, and the lymphocytes obtained labelled for CD25. Samples were analysed blindly by flow cytometry. <h3>RESULTS</h3> Median infiltration of lymphocytes expressing CD25, measured immunohistochemically, was higher in trial patients, as was the ratio of tumour to normal bowel infiltration. Flow cytometric analysis of fresh tumour from immunised patients showed a significantly higher percentage of lymphocytes expressing CD25 tumour infiltrating lymphocytes than their matched and unmatched controls. <h3>DISCUSSION</h3> The α subunit of the interleukin 2 receptor is increased on tumour infiltrating lymphocytes, in patients immunised with the colorectal cancer vaccine 105AD7. This suggests a population of activated lymphocytes capable of targeting 791Tgp72 expressing tumour cells, such as circulating micrometastases. 105AD7 may have a role as adjuvant therapy in early stage disease.
Dietary Carotenoids and Vitamins A, C, and E and Risk of Breast Cancer
Authors: S. Zhang, D. J. Hunter, M. R. Forman, B. A. Rosner, F. E. Speizer, G. A. Colditz, J. E. Manson, S. E. Hankinson, W. C. Willett
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Data on intake of specific carotenoids and breast cancer risk are limited. Furthermore, studies of vitamins A, C, and E in relation to breast cancer risk are inconclusive. We have conducted a large, prospective study to evaluate long-term intakes of these nutrients and breast cancer risk. METHODS: We examined, by use of multivariate analysis, associations between intakes of specific carotenoids, vitamins A, C, and E , consumption of fruits and vegetables, and breast cancer risk in a cohort of 83 234 women (aged 33-60 years in 1980) who were participating in the Nurses' Health Study. Through 1994, we identified 2697 incident cases of invasive breast cancer (784 premenopausal and 1913 postmenopausal). RESULTS: Intakes of β-carotene from food and supplements, lutein/zeaxanthin, and vitamin A from foods were weakly inversely associated with breast cancer risk in premenopausal women. Strong inverse associations were found for increasing quintiles of α-carotene, β -carotene, lutein/zeaxanthin, total vitamin C from foods, and total vitamin A among premenopausal women with a positive family history of breast cancer. An inverse association was also found for increasing quintiles of β-carotene among premenopausal women who consumed 15 g or more of alcohol per day. Premenopausal women who consumed five or more servings per day of fruits and vegetables had modestly lower risk of breast cancer than those who had less than two servings per day (relative risk [RR] = 0.77; 95% confidence interval [CI] = 0.58-1.02); this association was stronger among premenopausal women who had a positive family history of breast cancer (RR = 0.29; 95% CI = 0.13-0.62) or those who consumed 15 g or more of alcohol per day (RR = 0.53; 95% CI = 0.27-1.04). CONCLUSIONS: Consumption of fruits and vegetables high in specific carotenoids and vitamins may reduce premenopausal breast cancer risk.
Genetic basis of hemolytic anemia caused by pyrimidine 5′ nucleotidase deficiency
Authors: Anthony M. Marinaki, Emilia Escuredo, John A. Duley, H. Anne Simmonds, Adolfo Amici, Valeria Naponelli, Giulio Magni, Martin Seip, Isaac Ben-Bassat, Eric H. Harley, Swee Lay Thein, David C. Rees
Journal: Blood (2001)
SoxNeuro orchestrates central nervous system specification and differentiation in Drosophila and is only partially redundant with Dichaete
Authors: Enrico Ferrero, Bettina Fischer, Steven Russell
Journal: Genome biology (2014)

Sox proteins encompass an evolutionarily conserved family of transcription factors with critical roles in animal development and stem cell biology. In common with vertebrates, the Drosophila group B proteins SoxNeuro and Dichaete are involved in central nervous system development, where they play both similar and unique roles in gene regulation. Sox genes show extensive functional redundancy across metazoans, but the molecular basis underpinning functional compensation mechanisms at the genomic level are currently unknown.Using a combination of genome-wide binding analysis and gene expression profiling, we show that SoxNeuro directs embryonic neural development from the early specification of neuroblasts through to the terminal differentiation of neurons and glia. To address the issue of functional redundancy and compensation at a genomic level, we compare SoxNeuro and Dichaete binding, identifying common and independent binding events in wild-type conditions, as well as instances of compensation and loss of binding in mutant backgrounds.We find that early aspects of group B Sox functions in the central nervous system, such as stem cell maintenance and dorsoventral patterning, are highly conserved. However, in contrast to vertebrates, we find that Drosophila group B1 proteins also play prominent roles during later aspects of neural morphogenesis. Our analysis of the functional relationship between SoxNeuro and Dichaete uncovers evidence for redundant and independent functions for each protein, along with unexpected examples of compensation and interdependency, thus providing new insights into the general issue of transcription factor functional redundancy.
Chest radiographic abnormalities in HIV-infected African children: a longitudinal study
Authors: Richard D Pitcher, Carl J Lombard, Mark F Cotton, Stephen J Beningfield, Lesley Workman, Heather J Zar
Journal: Thorax (2015)

<h3>Background</h3> There is limited knowledge of chest radiographic abnormalities over time in HIV-infected children in resource-limited settings. <h3>Objective</h3> To investigate the natural history of chest radiographic abnormalities in HIV-infected African children, and the impact of antiretroviral therapy (ART). <h3>Methods</h3> Prospective longitudinal study of the association of chest radiographic findings with clinical and immunological parameters. Chest radiographs were performed at enrolment, 6-monthly, when initiating ART and if indicated clinically. Radiographic abnormalities were classified as normal, mild or moderate severity and considered persistent if present for 6 consecutive months or longer. An ordinal multiple logistic regression model assessed the association of enrolment and time-dependent variables with temporal radiographic findings. <h3>Results</h3> 258 children (median (IQR) age: 28 (13–51) months; median CD4+%: 21 (15–24)) were followed for a median of 24 (18–42) months. 70 (27%) were on ART at enrolment; 130 (50%) (median age: 33 (18–56) months) commenced ART during the study. 154 (60%) had persistent severe radiographic abnormalities, with median duration 18 (6–24) months. Among children on ART, 69% of radiographic changes across all 6-month transition periods were improvements, compared with 45% in those not on ART. Radiographic severity was associated with previous radiographic severity (OR=120.80; 95% CI 68.71 to 212.38), lack of ART (OR=1.72; 95% CI 1.29 to 2.27), enrolment age &lt;18 months (OR=1.39; 95% CI 1.06 to 1.83), diffuse, severe radiographic abnormality at enrolment (OR=2.18; 95% CI 1.33 to 3.56), hospitalisation for lower respiratory tract infection during the previous 6 months (OR=1.88; 95% CI 1.06 to 3.30) and length of follow-up: at 18–24 months (OR=0.66; 95% CI 0.49 to 0.90), and at 30–54 months (OR=0.42; 95% CI 0.32 to 0.56). <h3>Conclusions</h3> Most children had severe radiographic abnormalities persisting for at least 18 months. ART was beneficial, reducing the risk of radiographic deterioration or increasing the likelihood of radiological improvement.
Decisions About Dendritic Cells: Past, Present, and Future
Authors: Ralph M. Steinman
Journal: Annual Review of Immunology (2012)

A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells are required to explain how this remarkable system is energized and directed. I frame this article in terms of the major decisions that my colleagues and I have made in dendritic cell science and some of the guiding themes at the time the decisions were made. As a result of progress worldwide, there is now evidence of a central role for dendritic cells in initiating antigen-specific immunity and tolerance. The in vivo distribution and development of a previously unrecognized white cell lineage is better understood, as is the importance of dendritic cell maturation to link innate and adaptive immunity in response to many stimuli. Our current focus is on antigen uptake receptors on dendritic cells. These receptors enable experiments involving selective targeting of antigens in situ and new approaches to vaccine design in preclinical and clinical systems.
Mitochondrial ATP-Sensitive Potassium Channels Attenuate Matrix Ca <sup>2+</sup> Overload During Simulated Ischemia and Reperfusion
Authors: Mitsushige Murata, Masaharu Akao, Brian O’Rourke, Eduardo Marbán
Journal: Circulation Research (2001)

Mitochondrial ATP-sensitive potassium (mitoK ATP ) channels play a key role in ischemic preconditioning of the heart. However, the mechanism of cardioprotection remains controversial. We measured rhod-2 fluorescence in adult rabbit ventricular cardiomyocytes as an index of mitochondrial matrix Ca 2+ concentration ([Ca 2+ ] m ), using time-lapse confocal microscopy. To simulate ischemia and reperfusion (I/R), cells were exposed to metabolic inhibition (50 minutes) followed by washout with control solution. Rhod-2 fluorescence gradually increased during simulated ischemia and rose even further with reperfusion. The mitoK ATP channel opener diazoxide attenuated the accumulation of [Ca 2+ ] m during simulated I/R (EC 50 =18 μmol/L). These effects of diazoxide were blocked by the mitoK ATP channel antagonist 5-hydroxydecanoate (5HD). In contrast, inhibitors of the mitochondrial permeability transition (MPT), cyclosporin A and bongkrekic acid, did not alter [Ca 2+ ] m accumulation during ischemia, but markedly suppressed the surge in rhod-2 fluorescence during reperfusion. Measurements of mitochondrial membrane potential, ΔΨ m , in permeabilized myocytes revealed that diazoxide depolarized ΔΨ m (by 12% at 10 μmol/L, P &lt;0.01) in a 5HD-inhibitable manner. Our data support the hypothesis that attenuation of mitochondrial Ca 2+ overload, as a consequence of partial mitochondrial membrane depolarization by mitoK ATP channels, underlies cardioprotection. Furthermore, mitoK ATP channels and the MPT differentially affect mitochondrial calcium homeostasis: mitoK ATP channels suppress calcium accumulation during I/R, while the MPT comes into play only upon reperfusion.
Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer
Authors: Massimo Cristofanilli, G. Thomas Budd, Matthew J. Ellis, Alison Stopeck, Jeri Matera, M. Craig Miller, James M. Reuben, Gerald V. Doyle, W. Jeffrey Allard, Leon W.M.M. Terstappen, Daniel F. Hayes
Journal: New England Journal of Medicine (2004)

We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer.In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers.Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P<0.001) and shorter overall survival (10.1 months vs. >18 months, P<0.001). At the first follow-up visit after the initiation of therapy, this difference between the groups persisted (progression-free survival, 2.1 months vs. 7.0 months; P<0.001; overall survival, 8.2 months vs. >18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival.The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.
Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis
Authors: K Ohba, K Omagari, T Nakamura, N Ikuno, S Saeki, I Matsuo, H Kinoshita, J Masuda, H Hazama, I Sakamoto, S Kohno
Journal: Gut (1998)

Spontaneous regression of hepatocellular carcinoma is a rare phenomenon. Abscopal regression of tumours resulting from the effect of irradiation of a tissue on a remote non-irradiated tissue is also rare. The case of a 76 year old Japanese man with hepatocellular carcinoma that regressed after radiotherapy for thoracic vertebral bone metastasis is described. Serum levels of tumour necrosis factor-α increased after radiotherapy. The findings suggests that such abscopal related regression may be associated with host immune response, involving cytokines such as tumour necrosis factor-α.
PAMLX: A Graphical User Interface for PAML
Authors: B. Xu, Z. Yang
Journal: Molecular Biology and Evolution (2013)

This note announces pamlX, a graphical user interface/front end for the paml (for Phylogenetic Analysis by Maximum Likelihood) program package (Yang Z. 1997. PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci. 13:555–556; Yang Z. 2007. PAML 4: Phylogenetic analysis by maximum likelihood. Mol Biol Evol. 24:1586–1591). pamlX is written in C++ using the Qt library and communicates with paml programs through files. It can be used to create, edit, and print control files for paml programs and to launch paml runs. The interface is available for free download at http://abacus.gene.ucl.ac.uk/software/paml.html.
Patients with severe sepsis vary markedly in their ability to generate activated protein C
Authors: Patricia C. Y. Liaw, Charles T. Esmon, Kamyar Kahnamoui, Shelley Schmidt, Sarah Kahnamoui, Gary Ferrell, Suzanne Beaudin, Jim A. Julian, Jeffrey I. Weitz, Mark Crowther, Mark Loeb, Deborah Cook
Journal: Blood (2004)
Role of natriuretic peptides in ion transport mechanisms
Authors: Joseph I. Kourie, Megan J. Rive
Journal: Medicinal Research Reviews (1999)

Natriuretic peptides (NP) act as ligands on the guanylyl cyclase family of receptors. The NP binding site on these receptors is extracellular and the guanylyl cyclase and protein kinase domains are intracellular. The guanylyl cyclase receptor catalyzes the synthesis of the second messenger molecule, cGMP, which activates protein kinase. This in turn is involved in the phosphorylation of various ion transport proteins. Ion transport proteins, which are modulated by NP and are thought to underlie the natriuretic and diuretic actions of NP, include: (a) calcium-activated K+ channels; (b) ATP-sensitive K+ channels; (c) inwardly-rectifying K+ channels; (d) outwardly-rectifying K+ channels; (e) L-type Ca²+ channels; (f) Cl- channels including cystic fibrosis transmembrane conductance regulator Cl- channels; (g) Na+- K+ 2Cl- co-transporter; (h) Na+- K+ ATPase; (i) Na+ channels; (j) stretch-activated channels; and (k) water channels. It appears that NP modulate the kinetics, rather than the conductance, of ion channels. Some of these channels, like the Ca²+, ATP-sensitive K+ and stretch-activated channels, are also involved in NP secretion. In addition, the structural properties of the NP, e.g., ovCNP-22 and ovCNP-39, appear to confer on them the ability to form ion channels. These CNP-formed ion channels can modify the trans-membrane signal transduction and second messenger systems underlying NP-induced pathological effects. © 1999 John Wiley & Sons, Inc. Med Res Rev, 19, No. 1, 75–94, 1999.
Pulmonary Function, Body Composition, and Protein Catabolism in Adults with Cystic Fibrosis
Authors: ALINA A. IONESCU, LISETTE S. NIXON, STEPHEN LUZIO, VANESSA LEWIS-JENKINS, WILLIAM D. EVANS, MICHAEL D. STONE, DAVID R. OWENS, PHILIP A. ROUTLEDGE, DENNIS J. SHALE
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Increased survival in cystic fibrosis (CF) is associated with bone thinning and fat-free mass (FFM) loss. We hypothesized that the severity of lung disease would be associated with increased protein catabolism and systemic inflammatory status in clinically stable patients. Forty adults with CF and 22 age-matched healthy subjects were studied. Body composition was determined by dual-energy X-ray absorptiometry. Urinary pseudouridine (PSU), a marker of protein breakdown, and cross-linked N-telopeptides of type I collagen (NTx), a marker of bone connective tissue breakdown, serum tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and their soluble receptors were measured. A 3-d food intake diary revealed 21 patients had a low energy intake. Excretion of PSU (p = 0.019) and NTx (p < 0.01) was increased in patients and was inversely related to FEV(1); PSU (r = - 0.53, p = 0.001) and NTx (r = - 0.43, p < 0.01). Increased excretion of PSU and NTx (p < 0.05 for both) was also related to a low FFM. All inflammatory mediators were greater in patients and were related to PSU and NTx. Clinically stable adults were catabolic with both cellular and connective tissue protein breakdown, which was related to lung disease severity, systemic inflammation, and body composition.
Increased Parathyroid Hormone Gene Expression in Secondary Hyperparathyroidism of Experimental Uremia Is Reversed by Calcimimetics
Authors: Ronen Levi, Iddo Z. Ben-Dov, Vardit Lavi-Moshayoff, Maya Dinur, David Martin, Tally Naveh-Many, Justin Silver
Journal: Journal of the American Society of Nephrology (2005)

Most patients with chronic kidney disease develop secondary hyperparathyroidism with disabling systemic complications. Calcimimetic agents are effective tools in the management of secondary hyperparathyroidism, acting through allosteric modification of the calcium-sensing receptor (CaR) on the parathyroid gland (PT) to decrease parathyroid hormone (PTH) secretion and PT cell proliferation. This study showed that rats that were fed an adenine high-phosphorus diet had increased serum PTH and PTH mRNA levels at 7 and 21 d. For studying the effect of activation of the CaR by the calcimimetics R-568 on PTH gene expression, R-568 was given by gavage to uremic rats for the last 4 d of a 7-d adenine high-phosphorus diet. R-568 decreased both PTH mRNA and serum PTH levels. The effect of the calcimimetic on PTH gene expression was posttranscriptional and correlated with differences in protein-RNA binding and posttranslational modifications of the trans acting factor AUF1 in the PT. The AUF1 modifications as a result of uremia were reversed by treatment with R-568 to those of normal rats. Therefore, uremia and activation of the CaR mediated by calcimimetics modify AUF1 posttranslationally. These modifications in AUF1 correlate with changes in protein-PTH mRNA binding and PTH mRNA levels.
Unravelling the genomic mosaic of a ubiquitous genus of marine cyanobacteria
Authors: Alexis Dufresne, Martin Ostrowski, David J Scanlan, Laurence Garczarek, Sophie Mazard, Brian P Palenik, Ian T Paulsen, Nicole Tandeau de Marsac, Patrick Wincker, Carole Dossat, Steve Ferriera, Justin Johnson, Anton F Post, Wolfgang R Hess, Frédéric Partensky
Journal: Genome biology (2008)

Abstract Background The picocyanobacterial genus Synechococcus occurs over wide oceanic expanses, having colonized most available niches in the photic zone. Large scale distribution patterns of the different Synechococcus clades (based on 16S rRNA gene markers) suggest the occurrence of two major lifestyles ('opportunists'/'specialists'), corresponding to two distinct broad habitats ('coastal'/'open ocean'). Yet, the genetic basis of niche partitioning is still poorly understood in this ecologically important group. Results Here, we compare the genomes of 11 marine Synechococcus isolates, representing 10 distinct lineages. Phylogenies inferred from the core genome allowed us to refine the taxonomic relationships between clades by revealing a clear dichotomy within the main subcluster, reminiscent of the two aforementioned lifestyles. Genome size is strongly correlated with the cumulative lengths of hypervariable regions (or 'islands'). One of these, encompassing most genes encoding the light-harvesting phycobilisome rod complexes, is involved in adaptation to changes in light quality and has clearly been transferred between members of different Synechococcus lineages. Furthermore, we observed that two strains (RS9917 and WH5701) that have similar pigmentation and physiology have an unusually high number of genes in common, given their phylogenetic distance. Conclusion We propose that while members of a given marine Synechococcus lineage may have the same broad geographical distribution, local niche occupancy is facilitated by lateral gene transfers, a process in which genomic islands play a key role as a repository for transferred genes. Our work also highlights the need for developing picocyanobacterial systematics based on genome-derived parameters combined with ecological and physiological data.