tbuckley/cabot-search huggingface dataset:
Carboplatin plus gemcitabine in patients with inoperable or metastatic pancreatic cancer: a phase II multicenter study by the Hellenic Cooperative Oncology Group
Authors: N. Xiros, P. Papacostas, T. Economopoulos, G. Samelis, E. Efstathiou, E. Kastritis, H. Kalofonos, A. Onyenadum, D. Skarlos, A. Bamias, H. Gogas, D. Bafaloukos, E. Samantas, P. Kosmidis
Journal: Annals of Oncology (2005)
New leader commits Tory party to an NHS that is free to all
Authors: Faye van Emmerik
Journal: BMJ (2006)

In a move away from Thatcherite politics, David Cameron, the new leader of the Conservative party, committed his party to providing a health service that is free to everyone at the point of need.

But he said that if his party was elected to government he would increase the percentage of NHS services provided by the private sector beyond the 15% limit imposed by Labour.

In the launch of his new health policy at the King's Fund health research institute in London last week he said the Conservatives aimed to make the NHS “into a …
Can Gut Hormones Control Appetite and Prevent Obesity?
Authors: Owais B. Chaudhri, Katie Wynne, Stephen R. Bloom
Journal: Diabetes Care (2008)

The current obesity epidemic is fuelled by the availability of highly palatable, calorie-dense food, and the low requirement for physical activity in our modern environment. If energy intake exceeds energy use, the excess calories are stored as body fat. Although the body has mechanisms that act to maintain body weight over time, they primarily defend against starvation and are less robust in preventing the development of obesity. Knowledge of this homeostatic system that controls body weight has increased exponentially over the last decade and has revealed new possibilities for the treatment of obesity and its associated comorbidities. One therapeutic target is the development of agents based on the gastrointestinal hormones that control appetite. This review discusses the hormones oxyntomodulin, peptide YY, glucagon-like peptide 1, pancreatic polypeptide, and ghrelin and their emerging potential as anti-obesity treatments.
Feature-based attention in visual cortex
Authors: John H.R. Maunsell, Stefan Treue
Journal: Trends in Neurosciences (2006)

Although most studies of visual attention have examined the effects of shifting attention between different locations in the visual field, attention can also be directed to particular visual features, such as a color, orientation or a direction of motion. Single-unit studies have shown that attention to a feature modulates neuronal signals in a range of areas in monkey visual cortex. The location-independent property of feature-based attention makes it particularly well suited to modify selectively the neural representations of stimuli or parts within complex visual scenes that match the currently attended feature. This review is part of the TINS special issue on The Neural Substrates of Cognition.
Integration of Psychiatric and Vocational Services: A Multisite Randomized, Controlled Trial of Supported Employment
Authors: Judith A. Cook, Anthony F. Lehman, Robert Drake, William R. McFarlane, Paul B. Gold, H. Stephen Leff, Crystal Blyler, Marcia G. Toprac, Lisa A. Razzano, Jane K. Burke-Miller, Laura Blankertz, Michael Shafer, Susan A. Pickett-Schenk, Dennis D. Grey
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Although large-scale surveys indicate that patients with severe mental illness want to work, their unemployment rate is three to five times that of the general adult population. This multisite, randomized implementation effectiveness trial examined the impact of highly integrated psychiatric and vocational rehabilitation services on the likelihood of successful work outcomes. METHOD: At seven sites nationwide, 1,273 outpatients with severe mental illness were randomly assigned either to an experimental supported employment program or to a comparison/services-as-usual condition and followed for 24 months. Data collection involved monthly services tracking, semiannual in-person interviews, recording of all paid employment, and program ratings made by using a services-integration measure. The likelihood of competitive employment and working 40 or more hours per month was examined by using mixed-effects random regression analysis. RESULTS: Subjects served by models that integrated psychiatric and vocational service delivery were more than twice as likely to be competitively employed and almost 1½ times as likely to work at least 40 hours per month when the authors controlled for time, demographic, clinical, and work history confounds. In addition, higher cumulative amounts of vocational services were associated with better employment outcomes, whereas higher cumulative amounts of psychiatric services were associated with poorer outcomes. CONCLUSIONS: Supported employment models with high levels of integration of psychiatric and vocational services were more effective than models with low levels of service integration.
Effect of dysfunctional vascular endothelium on myocardial performance in isolated papillary muscles.
Authors: K Li, J L Rouleau, L J Andries, D L Brutsaert
Journal: Circulation Research (1993)

Vascular endothelium has been shown to modify the contractile characteristics of vascular smooth muscle, and endocardial endothelium has been shown to modify the contractile characteristics of adjacent myocardium. In this study, whether vascular endothelium also modifies the contractile characteristics of adjacent myocardium and whether these effects are additive to those of endocardial endothelium were investigated. Rabbit hearts (n = 54) were excised and mounted in a Langendorff preparation. Vascular reactivity was verified by acetylcholine infusion. One group of these hearts had Triton X-100 injected as a bolus into the coronaries to render the vascular endothelium dysfunctional. The other portion served as control hearts. Triton X-100 bolus injection resulted in little or no pathological changes on morphological examination; however, the vasodilatory response to acetylcholine in these hearts was abolished, suggesting vascular endothelial dysfunction. Vascular smooth muscle reactivity was verified in Triton X-100-injected hearts by nitroprusside infusion. In the control Langendorff-perfused hearts, there was little evidence of vascular endothelial dysfunction, with the coronary perfusion rate increasing from 8.9 +/- 0.4 to 11.0 +/- 0.3 ml/g per minute (p &lt; 0.01) in response to acetylcholine. All hearts were then removed, and right ventricular papillary muscles were excised for myocardial mechanical studies. Control Langendorff-perfused hearts had myocardial mechanical characteristics similar to those of muscles from 18 other control hearts without Langendorff perfusion, indicating that the Langendorff perfusion itself had little effect on myocardial mechanics. The muscles from the Triton X-100-injected Langendorff hearts had marked changes: a shortening of twitch duration (363 +/- 16 versus 449 +/- 9 msec, p &lt; 0.01) and decreases in total tension (2.2 +/- 0.2 versus 2.9 +/- 0.2 g/mm2, p &lt; 0.01), dT/dt (9 +/- 1 versus 12 +/- 1 g/mm2 per second, p &lt; 0.05), and maximum velocity of unloaded muscle shortening (Vmax) (0.89 +/- 0.06 versus 1.14 +/- 0.07 length at which maximum developed tension occurred [Lmax]/sec, p &lt; 0.05). Endocardial endothelial removal of the papillary muscles in the two control groups (with and without Langendorff perfusion) by Triton X-100 caused the same changes in twitch characteristics as occurred in muscles from the Langendorff-perfused hearts injected with Triton X-100 but with intact endocardial endothelium, suggesting that vascular endothelial dysfunction had similar effects on contractile characteristics as endocardial endothelial removal.(ABSTRACT TRUNCATED AT 400 WORDS)
Identification of Interleukin-13 Receptor α2 Peptide Analogues Capable of Inducing Improved Antiglioma CTL Responses
Authors: Junichi Eguchi, Manabu Hatano, Fumihiko Nishimura, Xinmei Zhu, Jill E. Dusak, Hidemitsu Sato, Ian F. Pollack, Walter J. Storkus, Hideho Okada
Journal: Cancer Research (2006)

Abstract Restricted and high-level expression of interleukin-13 receptor α2 (IL-13Rα2) in a majority of human malignant gliomas makes this protein an attractive vaccine target. We have previously described the identification of the IL-13Rα2345-353 peptide as a human leukocyte antigen-A2 (HLA-A2)–restricted CTL epitope. However, as it remains unclear how efficiently peptide-based vaccines can induce specific CTLs in patients with malignant gliomas, we have examined whether analogue epitopes could elicit heteroclitic antitumor T-cell responses versus wild-type peptides. We have created three IL-13Rα2 analogue peptides by substitutions of the COOH-terminal isoleucine (I) for valine (V) and the NH2-terminal tryptophan (W) for either alanine (A), glutamic acid (E), or nonsubstituted (W; designated as 1A9V, 1E9V, and 9V, respectively). In comparison with the native IL-13Rα2 epitope, the analogue peptides 9V and 1A9V displayed higher levels of binding affinity and stability in HLA-A2 complexes and yielded an improved stimulatory index for patient-derived, specific CTLs against the native epitope expressed by HLA-A2+ glioma cells. In HLA-A2-transgenic HHD mice, immunization with the peptides 9V and 1A9V induced enhanced levels of CTL reactivity and protective immunity against an intracranial challenge with IL13Rα2-expressing syngeneic tumors when compared with vaccines containing the native IL-13Rα2 epitope. These findings indicate highly immunogenic IL-13Rα2 peptide analogues may be useful for the development of vaccines capable of effectively expanding IL-13Rα2-specific, tumor-reactive CTLs in glioma patients. (Cancer Res 2006; 66(11): 5883-91)
Bone Morphogenetic Protein Signaling Modulates Myocardin Transactivation of Cardiac Genes
Authors: Thomas E. Callis, Dongsun Cao, Da-Zhi Wang
Journal: Circulation Research (2005)

Bone morphogenetic proteins (BMPs) play important roles in cardiovascular development. However, how BMP-signaling pathways regulate cardiac gene expression is less clear. We have previously identified myocardin as a cardiac and smooth muscle-specific transcriptional cofactor for serum response factor (SRF). Myocardin potently activates target gene expression by tethering with SRF bound to SRF-responsive elements, the CArG box. Here, we show that Smad1, an effector of the BMP-signaling pathway, synergistically activates myocardin-dependent cardiac gene expression. Interestingly, the CArG box is necessary and sufficient to mediate such synergy, whereas no obvious Smad-binding element appears to be involved. Consistent with their functional interaction, we find that myocardin and Smad1 proteins interact directly. Furthermore, myocardin protein levels were dramatically increased by BMP-2 treatment in cardiomyocytes. These findings suggest myocardin participates in a BMP signaling-dependent cardiac gene transcriptional program.
Correlation of quantitative changes of gastric mucosal glycoproteins with aspirin-induced gastric damage in rats.
Authors: Y Azuumi, S Ohara, K Ishihara, H Okabe, K Hotta
Journal: Gut (1980)

Quantitative changes of gastric mucosal glycoproteins with the gastric damage induced by acetylsalicylic acid (aspirin) in rat have been studied. Gastric injury was easily observed macroscopically within one hour after the oral administration of aspirin. The most striking changes occurred at five hours, and the injury was overcome within nine hours after dosing. The glycoproteins extracted from rat stomack with Tris buffer containing Triton X-100 were fractionated on Bio-Gel A-1.5 m column chromatography and divided into three fractions. The first peak, corresponding to gastric mucus macromolecular neutral and acidic glycoproteins with or without sulphate (Fr.I), was diminished after aspirin administration. A considerable alteration of Fr.I (49% of control) appeared at three hours, and a gradual return to the control value was observed subsequently. The changes in the amount of the glycoproteins were detected before the macroscopical changes of the mucosa. These results suggest that gastric ulceration induced by aspirin may be caused by a deficiency of gastric mucus macromolecular glycoproteins of gastric mucus.
Largest Genetic Survey to Date Shows Major Success for Giant Panda Breeding Programs
Authors: J. Caspermeyer
Journal: Molecular Biology and Evolution (2014)

Heroic worldwide conservation efforts have made great strides in saving China’s endangered national treasure, the giant panda. Now, in China, there are over 65 giant panda reserves that have been established and three large breeding centers. But despite these efforts, just 1,596 pandas remain in the wild. Breeding programs in conservation centers and zoos hope to save the panda by improving genetic diversity, avoid inbreeding and ultimately, introduce pandas back to the wild. Just how are these high-profile programs doing so far? Shan et al. (2014) performed the most comprehensive genetic survey so far. They evaluated the diversity of 240 captive giant pandas from four Chinese breeding centers locations (Wolong, Chengdu, Louguantai, and the Beijing zoo account for 64% of the 341 pandas kept in captivity). In good news for the breeding centers, high levels of genetic diversity and low levels of inbreeding were found in the captive populations, which indicate that the whole captive population is genetically healthy, and it is therefore unnecessary to capture more wild pandas for captive breeding. However, one center, the Louguantai population, faces a higher risk of inbreeding and requires urgent attention to correct, such as scientifically selected breeding pairs. Finally, the authors recommend that the selection of captive pandas for reintroduction into the wild should consider their geographic origin, genetic background, and genetic contribution. By combining the new molecular genetic data with pedigree data, the authors hope that panda research centers can successfully release pandas back into the wild.
The Mammalian Phenotype Ontology as a tool for annotating, analyzing and comparing phenotypic information.
Authors: Cynthia L Smith, Carroll-Ann W Goldsmith, Janan T Eppig
Journal: Genome biology (2004)

Abstract The Mammalian Phenotype (MP) Ontology enables robust annotation of mammalian phenotypes in the context of mutations, quantitative trait loci and strains that are used as models of human biology and disease. The MP Ontology supports different levels and richness of phenotypic knowledge and flexible annotations to individual genotypes. It continues to develop dynamically via collaborative input from research groups, mutagenesis consortia, and biological domain experts. The MP Ontology is currently used by the Mouse Genome Database and Rat Genome Database to represent phenotypic data.
CD4+ T Cell-Mediated Antigen-Specific Immunotherapy in a Mouse Model of Cervical Cancer
Authors: Dylan Daniel, Christopher Chiu, Enrico Giraudo, Masahiro Inoue, Lee A. Mizzen, N. Randall Chu, Douglas Hanahan
Journal: Cancer Research (2005)

Abstract A major agenda for tumor immunology is the generation of specific immune responses leading to the destruction of incipient and frank neoplasia. In this report, we show that a novel HPV16 E7 fusion protein can produce objective therapeutic responses against incipient cervical cancer in genetically engineered mice that express in the cervix the HPV16 early region genes implicated as causative agents in human cervical cancer. Although nonresponsive toward the HPV16 E7 oncoprotein in the CD8+ T-cell compartment by virtue of MHC haplotype, the mice were capable of mounting an induced CD4+ T-cell response against E7, and in addition developed spontaneous anti-E7 antibodies. HPV16/CD4−/− mice showed increased tumor burden indicative of CD4-mediated immune surveillance. Seeking to enhance the CD4 response, we immunized mice bearing incipient cervical cancer with a recombinant protein fusing E7 with a mycobacterial heat shock protein. The incidences of cervical carcinoma and of high-grade dysplasia (CIN 3) were consequently reduced by comparison to control mice. Thus, an HPV16 E7 immunogen holds promise for noninvasive treatment and prevention of human cervical cancer.
Lsh regulates LTR retrotransposon repression independently of Dnmt3b function
Authors: Donncha S Dunican, Hazel A Cruickshanks, Masako Suzuki, Colin A Semple, Tracey Davey, Robert J Arceci, John Greally, Ian R Adams, Richard R Meehan
Journal: Genome biology (2013)

DNA methylation contributes to genomic integrity by suppressing repeat-associated transposition. In addition to the canonical DNA methyltransferases, several auxiliary chromatin factors are required to maintain DNA methylation at intergenic and satellite repeats. The interaction between Lsh, a chromatin helicase, and the de novo methyltransferase Dnmt3b facilitates deposition of DNA methylation at stem cell genes, which are hypomethylated in Lsh −/− embryos. We wished to determine if a similar targeting mechanism operates to maintain DNA methylation at repetitive sequences. We mapped genome-wide DNA methylation patterns in Lsh −/− and Dnmt3b −/− somatic cells. DNA methylation is predominantly lost from specific genomic repeats in Lsh −/− cells: LTR -retrotransposons, LINE-1 repeats and mouse satellites. RNA-seq experiments demonstrate that specific IAP LTRs and satellites, but not LINE-1 elements, are aberrantly transcribed in Lsh −/− cells. LTR hypomethylation in Dnmt3b −/− cells is moderate, whereas IAP, LINE-1 and satellite elements are hypomethylated but silent. Repressed LINE-1 elements in Lsh −/− cells gain H3K4me3, but H3K9me3 levels are unaltered, indicating that DNA hypomethylation alone is not permissive for their transcriptional activation. Mis-expressed IAPs and satellites lose H3K9me3 and gain H3K4me3 in Lsh −/− cells. Our study emphasizes that regulation of repetitive elements by Lsh and DNA methylation is selective and context dependent. Silencing of repeats in somatic cells appears not to be critically dependent on Dnmt3b function. We propose a model where Lsh is specifically required at a precise developmental window to target de novo methylation to repeat sequences, which is subsequently maintained by Dnmt1 to enforce selective repeat silencing.
The Dscam Homologue of the Crustacean Daphnia Is Diversified by Alternative Splicing Like in Insects
Authors: Daniela Brites, Seanna McTaggart, Krystalynne Morris, Jobriah Anderson, Kelley Thomas, Isabelle Colson, Thomas Fabbro, Tom J. Little, Dieter Ebert, Louis Du Pasquier
Journal: Molecular Biology and Evolution (2008)

In insects, the homologue of the Down syndrome cell adhesion molecule (Dscam) is a unique case of a single-locus gene whose expression has extensive somatic diversification in both the nervous and immune systems. How this situation evolved is best understood through comparative studies. We describe structural, expression, and evolutionary aspects of a Dscam homolog in 2 species of the crustacean Daphnia. The Dscam of Daphnia generates up to 13,000 different transcripts by the alternative splicing of variable exons. This extends the taxonomic range of a highly diversified Dscam beyond the insects. Additionally, we have identified 4 alternative forms of the cytoplasmic tail that generate isoforms with or without inhibitory or activating immunoreceptor tyrosine–based motifs (ITIM and ITAM respectively), something not previously reported in insect's Dscam. In Daphnia, we detected exon usage variability in both the brain and hemocytes (the effector cells of immunity), suggesting that Dscam plays a role in the nervous and immune systems of crustaceans, as it does in insects. Phylogenetic analysis shows a high degree of amino acid conservation between Daphnia and insects except in the alternative exons, which diverge greatly between these taxa. Our analysis shows that the variable exons diverged before the split of the 2 Daphnia species and is in agreement with the nearest-neighbor model for the evolution of the alternative exons. The genealogy of the Dscam gene family from vertebrates and invertebrates confirmed that the highly diversified form of the gene evolved from a nondiversified form before the split of insects and crustaceans.
Pancreatitis induced by codeine: a case report with positive rechallenge
Authors: P Hastier, F Longo, M Buckley, R M Chichmanian, J P Delmont
Journal: Gut (1997)

A woman who developed acute pancreatitis following ingestion of low dose codeine, with positive rechallenge, is described. As this is the first case report of pancreatitis being induced solely by codeine, this side effect must be rare in view of the widespread consumption of this drug.
LYMPHOID CELLS MEDIATING TUMOR-SPECIFIC CYTOTOXICITY TO CARCINOMA OF THE URINARY BLADDER
Authors: C. O'Toole, V. Stejskal, P. Perlmann, M. Karlsson
Journal: The Journal of Experimental Medicine (1974)

Peripheral lymphocytes from patients with urinary bladder carcinoma and controls have been separated on the basis of rosette formation with sheep erythrocytes. The fractions were tested for tumor-specific cytotoxicity. The E rosette-forming cells of purity ⩾ 90% respond well in PHA-induced cytotoxicity but are totally inactive in the tumor assay. The non-E rosette-forming cells (purity ⩾ 91%) give enhanced activity in the tumor-specific cytotoxicity as well as in antibody-mediated target cell lysis in a model system. These data support the notion that the effector cells in cell-mediated immunity to carcinoma of the urinary bladder are members of the nonthymus-derived population of peripheral lymphocytes.
Effect of developed tension on the time courses of Ca2+ transients and tension in twitch contraction in ferret myocardium
Authors: Kimiaki Komukai, Satoshi Kurihara
Journal: Cardiovascular Research (1996)

Objectives: The aim of the study is to test the hypothesis that tension-dependent change in the affinity of cardiac troponin-C influences the time courses of Ca2+ transients and tension in twitch contraction. Methods: The Ca2+-sensitive photoprotein, aequorin, was microinjected into superficial cells of ferret papillary muscles and the Ca2+ transients and tension were simultaneously measured. The peak of developed tension was altered by changing the extracellular Ca2+ concentration, initial muscle length, and the application of 2,3-butanedione monoxime. Results: In each maneuver, the decay time of Ca2+ transients was prolonged and the tension relaxation time was shortened when the peak of developed tension was decreased. In contrast, when the peak of developed tension was increased, the decay time of Ca2+ transients was shortened and the tension relaxation time was prolonged. The decay time of Ca2+ transients measured with different maneuvers was negatively correlated with the peak tension and the tension relaxation time was positively correlated with the tension peak. Conclusions: The changes in the decay time of Ca2+ transients and the tension relaxation time indicate that developed tension modulates the affinity of troponin-C for Ca2+ in normal twitch contraction.