tbuckley/cabot-search huggingface dataset:
Analysis of specialized DNA polymerases expression in human gliomas: association with prognostic significance
Authors: Huibo Wang, Wenting Wu, Hong-Wei Wang, Shuai Wang, Yuanyuan Chen, Xiaotian Zhang, Jingmin Yang, Shiguang Zhao, Han-Fei Ding, Daru Lu
Journal: Neuro-Oncology (2010)

Aberrant activation of the translesion DNA synthesis (TLS) pathway has been suggested to play a role in tumorigenesis by promoting genetic mutations. We therefore examined glioma specimens for the expression of specialized DNA polymerases involved in TLS and assessed their prognostic significance. The expression levels of DNA polymerase κ (Pol κ), Pol ι, and Pol η were assessed in 40 primary glioma samples and 10 normal brain samples using quantitative real-time PCR and Western blot analysis. Their prognostic significance was evaluated using a population-based tissue microarray derived from a cohort of 104 glioma patients. Overexpression of Pol κ and Pol ι was observed in 57.5% (23-40) and 27.5% (11-40) of patients, respectively, whereas no significant expression of Pol η was seen in the specimens. Immunohistochemical studies revealed positive Pol κ and Pol ι staining in 72 (69.2%) and 33 (31.7%) of the 104 glioma specimens, respectively. Pol κ expression was associated with advanced stages of the disease. Both Pol κ- and Pol ι-positive staining were associated with shorter survival in glioma patients (P < .001 and P = .014, respectively). A multivariate survival analysis identified Pol κ as an independent prognostic factor for glioma patients (P < .001). These findings demonstrate, for the first time, that the expression of Pol κ and Pol ι is deregulated in gliomas, and upregulation of Pol κ is associated with poorer prognosis in glioma patients.
The nature of mental imagery: How null is the “null hypothesis”?
Authors: Gianfranco Dalla Barba, Victor Rosenthal, Yves-Marie Visetti
Journal: Behavioral and Brain Sciences (2002)

Is mental imagery pictorial? In Pylyshyn's view no empirical data provides convincing support to the “pictorial” hypothesis of mental imagery. Phenomenology, Pylyshyn says, is deeply deceiving and offers no explanation of why and how mental imagery occurs. We suggest that Pylyshyn mistakes phenomenology for what it never pretended to be. Phenomenological evidence, if properly considered, shows that mental imagery may indeed be pictorial, though not in the way that mimics visual perception. Moreover, Pylyshyn claims that the “pictorial hypothesis” is flawed because the interpretation of “picture-like” objects in mental imagery takes a homunculus. However, the same point can be objected to Pylyshyn's own conclusion: if imagistic reasoning involves the same mechanisms and the same forms of representation as those that are involved in general reasoning, if they operate on symbol-based representations of the kind recommended by Pylyshyn (1984) and Fodor (1975), don't we need a phenomenological homunculus to tell an imagined bear from the real one?
Nutritional effects on asthma aetiology and progression
Authors: P. A Cassano
Journal: Thorax (2009)

That nutrition affects health would not be argued by many, but questions about specific strategies to prevent chronic disease onset or mitigate disease progression do not yield easy answers. The role of diet in lung health, including chronic obstructive pulmonary disease (COPD), asthma and pulmonary function, has been reviewed repeatedly,1–4 but whether accumulated findings represent causal links remains an open question. Continuing to build the evidence base is critical, and efforts in this direction will contribute to the formulation of well-informed public health programmes and policies to guide individual, group and industry-level decision making.

In this issue of Thorax , Allen et al 5 report the results of a meta-analysis of observational epidemiological studies of vitamins A, C and E in relation to asthma over the life course with the purpose of estimating the effect size for each association ( see page 610 ). Their report summarises data from 40 publications, …
Two-dimensional echocardiographic examination of mitral valve abnormalities associated with coarctation of the aorta.
Authors: V Celano, D R Pieroni, J A Morera, J M Roland, R L Gingell
Journal: Circulation (1984)

Coarctation of the aorta is frequently associated with left ventricular inflow tract abnormalities that may be difficult to detect even at cardiac catheterization. This study involved patients with coarctation who underwent comprehensive two-dimensional echocardiographic investigations emphasizing visualization of the mitral valve and its apparatus. Of the 56 patients studied, 23 had completely normal study results, while in 33 (59%) results showed abnormalities of the mitral complex. The latter were divided into two groups: those having major mitral abnormalities (n = 12) and those with minor anomalies of the valve and apparatus (n = 21). The first group included patients with a supravalve stenosing ring, congenital mitral stenosis, mitral valve prolapse, and parachute mitral valve. Minor anomalies were classified as abnormalities of the papillary muscles, chordae tendineae, or combinations of both. No mitral malformations were found in a control group of patients. We conclude that two-dimensional echocardiography is a sensitive and accurate noninvasive method for assessing either significant or subtle forms of left ventricular inflow disease in patients with aortic coarctation. Its use is recommended for the acute medical and surgical management of these patients as well as for their long-term follow-up evaluation.
Effect of Fish Oil Supplementation on Graft Patency and Cardiovascular Events Among Patients With New Synthetic Arteriovenous Hemodialysis Grafts
Authors: Charmaine E. Lok, Louise Moist, Brenda R. Hemmelgarn, Marcello Tonelli, Miguel A. Vazquez, Marc Dorval, Matthew Oliver, Sandra Donnelly, Michael Allon, Kenneth Stanley
Journal: JAMA (2012)

PTIMAL HEMODIALYSIS REquires reliable vascular access.Current options include the arteriovenous fistula, synthetic arteriovenous graft, and central venous catheter, which in the United States are used in 55%, 21%, and 24% of prevalent patients receiving hemodialysis, respectively. 1The arteriovenous graft was the predominant vascular access type in North America during the early 1990s but fell out of favor owing to its high complication rates and associated costs.For example, thrombosis occurs in more than 50% of all arteriovenous grafts within 1 year after placement, necessitating a salvage procedure in more than 75%. 2,3Arteriovenous graft throm-bosis usually occurs at the venous anastomosis in proximity to a stenotic lesion resulting from aggressive neointimal hyperplasia. 4o date, multiple interventions have failed to convincingly or consistently re-
Hypersecretion of zymogen granules in the pathogenesis of cystic fibrosis
Authors: J. Blomfield, J. Dascalu, E. W. Van Lennep, J. M. Brown
Journal: Gut (1973)

In the submandibular saliva of 10 cystic fibrosis subjects and 10 controls the turbidity and elevated calcium, protein, and amylase concentrations of the cystic fibrosis secretions, and precipitation of calcium and phosphate in a ratio consistent with hydroxyapatite have been confirmed. By electron microscopy the centrifuged deposits of the cystic fibrosis saliva were seen to be composed predominantly of round or oval subcellular corpuscles. By comparison with submandibular gland, these corpuscles have been identified as inclusion bodies (spherules) from within zymogen granules. Hydroxyapatite crystals formed on standing in the cystic fibrosis saliva. Polyacrylamide gel disc electrophoresis of the cystic fibrosis centrifuged deposits showed five bands, one of which, band 4, was more prominent in the deposit than in the supernatant gels. Comparisons have been made between these results and other studies and have shown (1) elevated calcium and protein in cystic fibrosis exocrine secretions; (2) simultaneous secretion of calcium and enzymes from salivary glands, stomach, and pancreas; and (3) increased salivary secretion of calcium and protein in response to parasympathomimetic and sympathomimetic drugs. Hypersecretion of calcium-containing zymogen granules is postulated as the cause of obstruction in cystic fibrosis.
REVERSIBILITY OF LYMPHOMAS AND LYMPHOPROLIFERATIVE LESIONS DEVELOPING UNDER CYCLOSPORIN-STEROID THERAPY
Authors: T.E Starzl, K.A Porter, S Iwatsuki, J.T Rosenthal, B.W Shaw, R.W Atchison, M.A Nalesnik, M Ho, B.P Griffith, T.R Hakala, R.L Hardesty, R Jaffe, H.T Bahnson
Journal: The Lancet (1984)
The Unfolded Protein Response Mediates Adaptation to Exercise in Skeletal Muscle through a PGC-1α/ATF6α Complex
Authors: Jun Wu, Jorge L. Ruas, Jennifer L. Estall, Kyle A. Rasbach, Jang Hyun Choi, Li Ye, Pontus Boström, Heather M. Tyra, Robert W. Crawford, Kevin P. Campbell, D. Thomas Rutkowski, Randal J. Kaufman, Bruce M. Spiegelman
Journal: Cell Metabolism (2011)
Gastrostomy Tube for Vagotomy
Authors: W. G. Hendry
Journal: BMJ (1966)

dose of busulphan being regulated according to the white count.The dose varied considerably from nil to 8 mg.daily.During the last few months she became increasingly pigmented, had recurrent nausea, vomiting, and diarrhoea, lost a considerable amount of weight, and was very lethargic.Her blood-pressure tended to be low -about 105/60.The pigmentation was gen- eralized, but in addition she had marked pigmentation in the palmar creases.As in Dr. Harrold's patient, and patients reported previously,' ' the buccal mucous membranes were spared.Our patient showed a normal excretion of urinary 17-hydroxy-corticosteroids (10-12.6 mg./24 hrs.(Few)), which rose to 29.5 mg./24 hrs. on the third day of receiving Cortrophin-Zn 60 units intramuscularly twice daily.The patient had been off treatment with busulphan for five weeks prior to this test.Another interesting feature in this patient was a very low serum calcium, the levels varying between 4.9 and 5.6 mg./100 ml.The patient complained of tingling in her limbs, and Chvostek's and Trousseau's signs were positive.The plasma proteins were normal-albumin 3.8 g./100 ml. and globulin 2.1 g./100 ml.There was no evidence of malabsorption, the xylose ex- cretion test and the faecal excretion of fat being normal.The urinary calciums were low, being 3.5 to 13 mg./24hrs.The serum calcium rose to 7.5 mg./100 ml. and tetany could no longer be elicited following the administration of calcium gluconate, 16 g.daily, and calciferol, 50,000 units daily.Hypocalcaemia would seem to be a rare finding in patients with myeloid leukaemia, although one instance has recently been reported.2In this patient the serum calcium was 7.4 mg./100 ml. and there were no signs and symptoms of tetany.We will be report- ing our patient in more detail elsewhere.
Minister denies councils will use public health money for filling potholes in roads
Authors: A. O'Dowd
Journal: BMJ (2011)

Local authorities will not be able to use public health funding for questionable purposes such as filling in potholes in roads once they take control of public health budgets, MPs have been told.

MPs on the parliamentary health select committee tackled government witnesses as part of their final evidence session of the ongoing inquiry into public health on 19 July.

Several concerns about how public health money will be spent once it passes into the control of local authorities as part of the NHS reforms had been brought to the attention of the committee.

MPs asked about fears that local authorities would spend public health funds on what might seem to be …
Aβ reduction in BACE1 heterozygous null 5XFAD mice is associated with transgenic APP level
Authors: Katherine R Sadleir, William A Eimer, Sarah L Cole, Robert Vassar
Journal: Molecular Neurodegeneration (2015)

The β-secretase, BACE1, cleaves APP to initiate generation of the β-amyloid peptide, Aβ, that comprises amyloid plaques in Alzheimer's disease (AD). Reducing BACE1 activity is an attractive therapeutic approach to AD, but complete inhibition of BACE1 could have mechanism-based side-effects as BACE1−/− mice show deficits in axon guidance, myelination, memory, and other neurological processes. Since BACE1+/− mice appear normal there is interest in determining whether 50% reduction in BACE1 is potentially effective in preventing or treating AD. APP transgenic mice heterozygous for BACE1 have decreased Aβ but the extent of reduction varies greatly from study to study. Here we assess the effects of 50% BACE1 reduction on the widely used 5XFAD mouse model of AD. 50% BACE1 reduction reduces Aβ42, plaques, and BACE1-cleaved APP fragments in female, but not in male, 5XFAD/BACE1+/− mice. 5XFAD/BACE1+/+ females have higher levels of Aβ42 and steady-state transgenic APP than males, likely caused by an estrogen response element in the transgene Thy-1 promoter. We hypothesize that higher transgenic APP level in female 5XFAD mice causes BACE1 to no longer be in excess over APP so that 50% BACE1 reduction has a significant Aβ42 lowering effect. In contrast, the lower APP level in 5XFAD males allows BACE1 to be in excess over APP even at 50% BACE1 reduction, preventing lowering of Aβ42 in 5XFAD/BACE1+/− males. We also developed and validated a dot blot assay with an Aβ42-selective antibody as an accurate and cost-effective alternative to ELISA for measuring cerebral Aβ42 levels. 50% BACE1 reduction lowers Aβ42 in female 5XFAD mice only, potentially because BACE1 is not in excess over APP in 5XFAD females with higher transgene expression, while BACE1 is in excess over APP in 5XFAD males with lower transgene expression. Our results suggest that greater than 50% BACE1 inhibition might be necessary to significantly lower Aβ, given that BACE1 is likely to be in excess over APP in the human brain. Additionally, in experiments using the 5XFAD mouse model, or other Thy-1 promoter transgenic mice, equal numbers of male and female mice should be used, in order to avoid artifactual gender-related differences.
Extracellular Superoxide Dismutase Is a Major Determinant of Nitric Oxide Bioavailability
Authors: Oliver Jung, Stefan L. Marklund, Helmut Geiger, Thierry Pedrazzini, Rudi Busse, Ralf P. Brandes
Journal: Circulation Research (2003)

The bioavailability of nitric oxide (NO) within the vascular wall is limited by superoxide anions (O2.-). The relevance of extracellular superoxide dismutase (ecSOD) for the detoxification of vascular O2.- is unknown. We determined the involvement of ecSOD in the control of blood pressure and endothelium-dependent responses in angiotensin II-induced hypertension and renovascular hypertension induced by the two-kidney, one-clip model in wild-type mice and mice lacking the ecSOD gene. Blood pressure was identical in sham-operated ecSOD+/+ and ecSOD-/- mice. After 6 days of angiotensin II-treatment and 2 and 4 weeks after renal artery clipping, blood pressure was significantly higher in ecSOD-/- than ecSOD+/+ mice. Recombinant ecSOD selectively decreased blood pressure in hypertensive ecSOD-/- mice, whereas ecSOD had no effect in normotensive and hypertensive ecSOD+/+ mice. Compared with sham-operated ecSOD+/+ mice, sham-operated ecSOD-/- mice exhibited attenuated acetylcholine-induced relaxations. These responses were further depressed in vessels from clipped animals. Vascular O2.-, as measured by lucigenin chemiluminescence, was higher in ecSOD-/- compared with ecSOD+/+ mice and was increased by clipping. The antioxidant tiron normalized relaxations in vessels from sham-operated and clipped ecSOD-/-, as well as from clipped ecSOD+/+ mice. In contrast, in vivo application of ecSOD selectively enhanced endothelium-dependent relaxation in vessels from ecSOD-/- mice. These data reveal that endogenous ecSOD is a major antagonistic principle to vascular O2.-, controlling blood pressure and vascular function in angiotensin II-dependent models of hypertension. ecSOD is expressed in such an abundance that even in situations of high oxidative stress no relative lack of enzyme activity occurs.
T-cell–depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect
Authors: Edwin Alyea, Edie Weller, Robert Schlossman, Christine Canning, Iain Webb, Deborah Doss, Peter Mauch, Karen Marcus, David Fisher, Andrea Freeman, Bijal Parikh, John Gribben, Robert Soiffer, Jerome Ritz, Kenneth Anderson
Journal: Blood (2001)
Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy
Authors: Adam Lister, Taoufik Nedjadi, Neil R Kitteringham, Fiona Campbell, Eithne Costello, Bryony Lloyd, Ian M Copple, Samantha Williams, Andrew Owen, John P Neoptolemos, Chris E Goldring, B Kevin Park
Journal: Molecular Cancer (2011)

Abstract Background Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for proteasomal degradation. The Nrf2/Keap1 system is dysregulated in lung, head and neck, and breast cancers and this affects cellular proliferation and response to therapy. Here, we have investigated the integrity of the Nrf2/Keap1 system in pancreatic cancer. Results Keap1, Nrf2 and the Nrf2 target genes AKR1c1 and GCLC were detected in a panel of five pancreatic cancer cell lines. Mutation analysis of NRF2 exon 2 and KEAP1 exons 2-6 in these cell lines identified no mutations in NRF2 and only synonomous mutations in KEAP1 . RNAi depletion of Nrf2 caused a decrease in the proliferation of Suit-2, MiaPaca-2 and FAMPAC cells and enhanced sensitivity to gemcitabine (Suit-2), 5-flurouracil (FAMPAC), cisplatin (Suit-2 and FAMPAC) and gamma radiation (Suit-2). The expression of Nrf2 and Keap1 was also analysed in pancreatic ductal adenocarcinomas (n = 66 and 57, respectively) and matching normal benign epithelium (n = 21 cases). Whilst no significant correlation was seen between the expression levels of Keap1 and Nrf2 in the tumors, interestingly, Nrf2 staining was significantly greater in the cytoplasm of tumors compared to benign ducts (P &lt; 0.001). Conclusions Expression of Nrf2 is up-regulated in pancreatic cancer cell lines and ductal adenocarcinomas. This may reflect a greater intrinsic capacity of these cells to respond to stress signals and resist chemotherapeutic interventions. Nrf2 also appears to support proliferation in certain pancreatic adenocarinomas. Therefore, strategies to pharmacologically manipulate the levels and/or activity of Nrf2 may have the potential to reduce pancreatic tumor growth, and increase sensitivity to therapeutics.
Spreading pigmented actinic keratoses
Authors: M.P. JAMES, G.C. WELLS, I.W. WHIMSTER
Journal: British Journal of Dermatology (2006)

The clinical and histological features of ten pigmented keratoses arising on the face are described. They were all greater than 1.5 cm in diameter and had been spreading centrifugally. They were variably pigmented and possessed either a smooth, verrucous or slightly scaly surface. Two lesions had progressed to become pigmented squamous cell carcinomas.
Research-intensive cancer care in the NHS in the UK
Authors: D. Cameron, M. Stead, N. Lester, M. Parmar, R. Haward, T. Maughan, R. Wilson, A. Spaull, H. Campbell, R. Hamilton, D. Stewart, L. O'Toole, D. Kerr, V. Potts, R. Moser, M. Cooper, K. Poole, J. Darbyshire, R. Kaplan, M. Seymour, P. Selby
Journal: Annals of Oncology (2011)
Differences in the Management of Type 1 Diabetes Among Adults Under Excellent Control Compared With Those Under Poor Control in the T1D Exchange Clinic Registry
Authors: Jill H. Simmons, Vincent Chen, Kellee M. Miller, Janet B. McGill, Richard M. Bergenstal, Robin S. Goland, David M. Harlan, Joseph F. Largay, Elaine M. Massaro, Roy W. Beck
Journal: Diabetes Care (2013)

OBJECTIVE Optimizing glycemic control in type 1 diabetes is important to minimize the risk of complications. We used the large T1D Exchange clinic registry database to identify characteristics and diabetes management techniques in adults with type 1 diabetes, differentiating those under excellent glycemic control from those with poorer control. RESEARCH DESIGN AND METHODS The cross-sectional analysis included 627 participants with HbA1c &amp;lt;6.5% (excellent control) and 1,267 with HbA1c ≥8.5% (fair/poor control) at enrollment who were ≥26 years of age (mean ± SD 45.9 ± 13.2 years), were not using continuous glucose monitoring, and had type 1 diabetes for ≥2 years (22.8 ± 13.0 years). RESULTS Compared with the fair/poor control group, participants in the excellent control group had higher socioeconomic status, were more likely to be older and married, were less likely to be overweight, were more likely to exercise frequently, and had lower total daily insulin dose per kilogram (P &amp;lt; 0.0001 for each). Excellent control was associated with more frequent self-monitoring of blood glucose (SMBG), giving mealtime boluses before a meal rather than at the time of or after a meal, performing SMBG before giving a bolus, and missing an insulin dose less frequently (P &amp;lt; 0.0001 for each). Frequency of severe hypoglycemia was similar between groups, whereas diabetic ketoacidosis was more common in the fair/poor control group. CONCLUSIONS Diabetes self-management related to insulin delivery, glucose monitoring, and lifestyle tends to differ among adults with type 1 diabetes under excellent control compared with those under poorer control. Future studies should focus on modifying diabetes management skills in adult type 1 diabetes patients with suboptimal glycemic control.
Appropriate Models for the Management of Infectious Diseases
Authors: Helen J Wearing, Pejman Rohani, Matt J Keeling
Journal: PLoS Medicine (2005)

Mathematical models have become invaluable management tools for epidemiologists, both shedding light on the mechanisms underlying observed dynamics as well as making quantitative predictions on the effectiveness of different control measures. Here, we explain how substantial biases are introduced by two important, yet largely ignored, assumptions at the core of the vast majority of such models.First, we use analytical methods to show that (i) ignoring the latent period or (ii) making the common assumption of exponentially distributed latent and infectious periods (when including the latent period) always results in underestimating the basic reproductive ratio of an infection from outbreak data. We then proceed to illustrate these points by fitting epidemic models to data from an influenza outbreak. Finally, we document how such unrealistic a priori assumptions concerning model structure give rise to systematically overoptimistic predictions on the outcome of potential management options.This work aims to highlight that, when developing models for public health use, we need to pay careful attention to the intrinsic assumptions embedded within classical frameworks.