tbuckley/cabot-search huggingface dataset:
Abstract 2028: Krüppel-like factor 4 null mouse embryonic fibroblasts exhibit DNA repair defects post exposure to gamma-irradiation
Authors: Hagos Engda, Vincent W. Yang, Bing Yu
Journal: Cancer Research (2012)

Abstract BACKGROUND: Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that exerts a potent inhibitory effect on cell cycle progression. KLF4 functions as a tumor suppressor in colorectal cancer and is involved in regulating centrosome duplication. Abnormal amplification of centrosomes has been shown to contribute to genetic instability by increasing the frequency of mitotic defects. AIM: To determine whether KLF4 is involved in maintaining genetic stability during cell division. METHODS: Mice heterozygous for the Klf4 alleles (Klf4+/−) on a C57BL/6 background were crossbred. Mouse embryonic fibroblasts (MEFs) that are wild type (Klf4+/+), heterozygous (Klf4+/−) or null (Klf4−/−) for the Klf4 alleles were derived from day-13.5 embryos. Post-senescence MEFs were derived by passing cells to senescence and maintaining them in culture until they spontaneously regained proliferative. Immuno-detection of histone variant γ-H2AX was performed to assess chromosome integrity. The levels of cell cycle regulators such as Cdk2, Cyclin E, and Cyclin D were determined by Western blotting. The presence of double strand breaks (DSB) was determined by western blot and immunofluorescence for histone variant -H2AX contains nuclear foci. Flow cytometry has been used to determine the level of DNA damage in both wildtype and klf4 null cells following gamma-irradiation. Furthermore, Expression profiles of fibroblasts isolated from mouse embryos wild type or null for the Klf4 alleles were examined by DNA microarrays. RESULTS: Cells that exhibits DSBs in their DNA can develop genomic instability, which can result in cancer formation. Compared to Klf4+/+ and Klf4−/− MEFs exposed to α-irradiation showed time-dependent increase in levels of histone variant -H2AX that persisted for up to 48 hours after the α-irradiation. On the other hand, Klf4+/+ halt cell cycle progression to allow repair of DNA damage. Western blot analysis showed that Cdk2, Cyclin E, Cyclin D and histone variant -H2AX expression were high in Klf4−/− MEFs. Furthermore, we found many of the down-regulated genes in Klf4-null MEFs encode DNA repair, and antioxidant genes. CONCLUSIONS: Results of this study demonstrate that Klf4 null mouse embryonic fibroblasts exhibit an impaired DNA damage response post gamma irradiation, when compared to wild-type cells. This data strongly suggest that the role for Klf4 in DNA damage repair in mouse embryonic fibroblast cells. These results indicate that KLF4 plays a crucial role in maintaining genetic stability and support the previous findings that KLF4 is a tumor suppressor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2028. doi:1538-7445.AM2012-2028
Skin recruitment of monomyeloid precursors involves human herpesvirus‐6 reactivation in drug allergy
Authors: H. Hashizume, T. Fujiyama, J. Kanebayashi, Y. Kito, M. Hata, H. Yagi
Journal: Allergy (2013)

In drug-induced hypersensitivity syndrome (DIHS), latent human herpesvirus (HHV)-6 is frequently reactivated in association with flaring of symptoms such as fever and hepatitis. We recently demonstrated an emergence of monomyeloid precursors expressing HHV-6 antigen in the circulation during this clinical course.To clarify the mechanism of HHV-6 reactivation, we immunologically investigated peripheral blood mononuclear cells (PBMCs), skin-infiltrating cells, and lymphocytes expanded from skin lesions of patients with DIHS.The circulating monomyeloid precursors in the patients with DIHS were mostly CD11b(+) CD13(+) CD14(-) CD16(high) and showed substantial expression of skin-associated molecules, such as CCR4. CD13(+) CD14(-) cells were also found in the DIHS skin lesions, suggesting skin recruitment of this cell population. We detected high levels of high-mobility group box (HMGB)-1 in blood and skin lesions in the active phase of patients with DIHS and showed that recombinant HMGB-1 had functional chemoattractant activity for monocytes/monomyeloid precursors in vitro. HHV-6 infection of the skin-resident CD4(+) T cells was confirmed by the presence of its genome and antigen. This infection was likely to be mediated by monomyeloid precursors recruited to the skin, because normal CD4(+) T cells gained HHV-6 antigen after in vitro coculture with highly virus-loaded monomyeloid precursors from the patients.Our results suggest that monomyeloid precursors harboring HHV-6 are navigated by HMGB-1 released from damaged skin and probably cause HHV-6 transmission to skin-infiltrating CD4(+) T cells, which is an indispensable event for HHV-6 replication. These findings implicate the skin as a cryptic and primary site for initiating HHV-6 reactivation.
PrPSc accumulation in neuronal plasma membranes links Notch-1 activation to dendritic degeneration in prion diseases
Authors: Stephen J DeArmond, Krystyna Bajsarowicz
Journal: Molecular Neurodegeneration (2010)

Prion diseases are disorders of protein conformation in which PrPC, the normal cellular conformer, is converted to an abnormal, protease-resistant conformer rPrPSc. Approximately 80% of rPrPSc accumulates in neuronal plasma membranes where it changes their physical properties and profoundly affects membrane functions. In this review we explain how rPrPSc is transported along axons to presynaptic boutons and how we envision the conversion of PrPC to rPrPSc in the postsynaptic membrane. This information is a prerequisite to the second half of this review in which we present evidence that rPrPSc accumulation in synaptic regions links Notch-1 signaling with the dendritic degeneration. The hypothesis that the Notch-1 intracellular domain, NICD, is involved in prion disease was tested by treating prion-infected mice with the γ-secretase inhibitor (GSI) LY411575, with quinacrine (Qa), and with the combination of GSI + Qa. Surprisingly, treatment with GSI alone markedly decreased NICD but did not prevent dendritic degeneration. Qa alone produced near normal dendritic trees. The combined GSI + Qa treatment resulted in a richer dendritic tree than in controls. We speculate that treatment with GSI alone inhibited both stimulators and inhibitors of dendritic growth. With the combined GSI + Qa treatment, Qa modulated the effect of GSI perhaps by destabilizing membrane rafts. GSI + Qa decreased PrPSc in the neocortex and the hippocampus by 95%, but only by 50% in the thalamus where disease was begun by intrathalamic inoculation of prions. The results of this study indicate that GSI + Qa work synergistically to prevent dendrite degeneration and to block formation of PrPSc.
Simple education reduces inappropriate blood glucose self monitoring in type 2 diabetes, study shows
Authors: S. Mayor
Journal: BMJ (2015)

A simple education and patient review programme for GPs reduced the proportion of patients with type 2 diabetes not treated with insulin who were inappropriately self monitoring their blood glucose by 20% over four years, a UK general practice study has shown.1

Many patients currently have routine blood glucose testing prescribed, and the number is increasing despite a lack of evidence that it improves glycaemic control or hypoglycaemia. So researchers investigated whether introducing local guidelines for GPs recommending individual patient review and information for patients could …
ACUTE HEMORRHAGIC PANCREATITIS: A CASE PRESENTING YELLOW DISCOLORATION AT THE UMBILICUS
Authors: Lloyd B. Johnston
Journal: JAMA (1930)

A moderately obese married woman, aged 37, whom I was asked to see after she had been ill for three days, gave a past history that indicated the presence of flatulence and eructation for four years. For two years preceding the present illness she had had increasingly frequent attacks of nausea, vomiting and upper right abdominal pain which radiated to the right scapular region and for which she was given morphine hypodermics on several occasions. Her present illness began with acute epigastric pain soon followed by nausea and vomiting early in the morning while she was in bed. When I saw her she appeared very ill and was in marked distress one hour after the administration of a hypodermic dose of morphine. The temperature was 100.2 F., pulse 90, respiration 20. The body was warm but the hands were cold and clammy. There was no jaundice or cyanosis. Respirations were
On the state of the public ill health: premature mortality in the United Kingdom and Europe.
Authors: J C Catford, S Ford
Journal: BMJ (1984)

Recently published data on mortality in the European Economic Community and Scandinavia convincingly showed that mortality among men and women aged 45-64 was considerably higher in the United Kingdom than elsewhere. This applied to deaths due to circulatory and respiratory disease, cancer, and all causes. For example, in 1980 in Scotland twice as many, or more, women aged 55-64 per 100 000 died of heart disease than in Belgium, Denmark, France, Greece, West Germany, the Netherlands, Norway, and Sweden. Reductions in mortality from all causes during 1950-80 in the United Kingdom did not match those in other countries, such as Finland and France. Whether the public in the United Kingdom knows about its relatively poor mortality state is doubtful. To secure improved funding of appropriate preventive and treatment services directed at reducing premature mortality, public awareness should be raised urgently so that politicians and political parties will respond quickly in a way that the problem demands.
1004-60 Atheromas at the LAD Origin Develop Opposite the Flow Divider: Implications Regarding the Role of Hemodynamic Shear in Atherogenesis Derived from Intravascular Ultrasound
Authors: Bruce J. Kimura, Robert J. Russo, Valmik Bhargava, Anthony N. DeMaria
Journal: Journal of the American College of Cardiology (1995)
Development of Novel Activin-Targeted Therapeutics
Authors: Justin L Chen, Kelly L Walton, Sara L Al-Musawi, Emily K Kelly, Hongwei Qian, Mylinh La, Louis Lu, George Lovrecz, Mark Ziemann, Ross Lazarus, Assam El-Osta, Paul Gregorevic, Craig A Harrison
Journal: Molecular Therapy (2014)

Soluble activin type II receptors (ActRIIA/ActRIIB), via binding to diverse TGF-β proteins, can increase muscle and bone mass, correct anemia or protect against diet-induced obesity. While exciting, these multiple actions of soluble ActRIIA/IIB limit their therapeutic potential and highlight the need for new reagents that target specific ActRIIA/IIB ligands. Here, we modified the activin A and activin B prodomains, regions required for mature growth factor synthesis, to generate specific activin antagonists. Initially, the prodomains were fused to the Fc region of mouse IgG2A antibody and, subsequently, "fastener" residues (Lys(45), Tyr(96), His(97), and Ala(98); activin A numbering) that confer latency to other TGF-β proteins were incorporated. For the activin A prodomain, these modifications generated a reagent that potently (IC(50) 5 nmol/l) and specifically inhibited activin A signaling in vitro, and activin A-induced muscle wasting in vivo. Interestingly, the modified activin B prodomain inhibited both activin A and B signaling in vitro (IC(50) ~2 nmol/l) and in vivo, suggesting it could serve as a general activin antagonist. Importantly, unlike soluble ActRIIA/IIB, the modified prodomains did not inhibit myostatin or GDF-11 activity. To underscore the therapeutic utility of specifically antagonising activin signaling, we demonstrate that the modified activin prodomains promote significant increases in muscle mass.
Urbanization, Physical Activity, and Metabolic Health in Sub-Saharan Africa
Authors: Felix K. Assah, Ulf Ekelund, Soren Brage, Jean Claude Mbanya, Nicholas J. Wareham
Journal: Diabetes Care (2011)

We examined the independent associations between objectively measured free-living physical activity energy expenditure (PAEE) and the metabolic syndrome in adults in rural and urban Cameroon.PAEE was measured in 552 rural and urban dwellers using combined heart rate and movement sensing over 7 continuous days. The metabolic syndrome was defined using the National Cholesterol Education Program-Adult Treatment Panel III criteria.Urban dwellers had a significantly lower PAEE than rural dwellers (44.2 ± 21.0 vs. 59.6 ± 23.7 kJ/kg/day, P < 0.001) and a higher prevalence of the metabolic syndrome (17.7 vs. 3.5%, P < 0.001). In multivariate regression models adjusted for possible confounders, each kJ/kg/day of PAEE was associated with a 2.1% lower risk of prevalent metabolic syndrome (odds ratio 0.98, P = 0.03). This implies a 6.5 kJ/kg/day difference in PAEE, equivalent to 30 min/day of brisk walking, corresponds to a 13.7% lower risk of prevalent metabolic syndrome. The population attributable fraction of prevalent metabolic syndrome due to being in the lowest quartile of PAEE was 26.3% (25.3% in women and 35.7% in men).Urban compared with rural residence is associated with lower PAEE and higher prevalence of metabolic syndrome. PAEE is strongly independently associated with prevalent metabolic syndrome in adult Cameroonians. Modest population-wide changes in PAEE may have significant benefits in terms of reducing the emerging burden of metabolic diseases in sub-Saharan Africa.
568 IMMUNOLOGICAL EVIDENCE FOR RESOLVED HBVINFECTION IN HEALTHY SERONEGATIVE SEXUAL PARTNERS OF PATIENTS WITH CHRONIC HBV INFECTION
Authors: S. Meya, J. Wiegand, V. Schlaphoff, M.P. Manns, J. Mossner, H. Wedemeyer, H.L. Tillmann
Journal: Journal of Hepatology (2008)
Dexamethasone Intravitreal Implant in Patients with Macular Edema Related to Branch or Central Retinal Vein Occlusion
Authors: Julia A. Haller, Francesco Bandello, Rubens Belfort, Mark S. Blumenkranz, Mark Gillies, Jeffrey Heier, Anat Loewenstein, Young Hee Yoon, Jenny Jiao, Xiao-Yan Li, Scott M. Whitcup
Journal: Ophthalmology (2011)
Internal Medicine: Cardiology
Authors: Leon Resnekov
Journal: JAMA (1981)

Every decade lays claim to important conceptual and practical advances in medicine. Perhaps it is no exaggeration to believe that the last 30 years may well be considered the "golden years" of modern cardiology. New knowledge is part of a continuum of studies and investigations previously conducted, and there are times when such advances continue at an exciting pace such as we have seen during the last three decades. How has this come about? The clinician has had the challenge of a seemingly endless number of patients who suffer cardiac disease; the basic researcher has met the challenge of a parallel and equally exciting development in cellular biology. This dual approach has resulted in a better fundamental understanding by the cardiologist of the disease entities he is striving to cure; the many unanswered questions posed by the clinician become, in turn, an important challenge to the basic scientist. Lasting advances
Surgical aspects of bacterial endocarditis.
Authors: T A English, J K Ross
Journal: Thorax (1972)

Forty patients with a previous history of bacterial endocarditis were treated surgically between December 1967 and August 1971. Of 28 patients who had elective valve replacements there were four hospital deaths and one late death. Seven patients underwent emergency operation for intractable heart failure before completion of antibiotic treatment, six survived operation and there was one late death. Six patients had operations for infection on pre-existing valve substitutes, of whom three were treated as emergencies. There were two hospital and no late deaths. 78% of all patients were alive and well four years to nine months after operation.  These results confirm that in addition to elective valve replacement surgery has an important role both in the treatment of intractable heart failure during the infective stage of bacterial endocarditis and in the eradication of infection on cardiac prostheses.
Abstract 5273: VBIM technology identifies beta-catenin-like protein (BCLP) as a novel negative regulator of NF-kB
Authors: Rasika Mundade, Tao Lu
Journal: Cancer Research (2014)

Abstract Colon cancer is the second leading cause of cancer related deaths in the United States. The nuclear factor kB (NF-kB) is an important family of transcription factors whose aberrant activation has been found in many types of cancer, including colon cancer. Therefore, understanding the regulation of NF-kB is of ultimate importance for cancer therapy. The purpose of this study is to use a novel validation-based insertional mutagenesis (VBIM) strategy to identify novel regulators of NF-kB, and further evaluate their roles in the regulation of NF-kB signaling in colon cancer cells. We infected D1 cells (293 derived cells with hyper active NF-kB activity) with VBIM virus to cause the overexpression of negative regulators of NF-kB, and then further selected the mutant cells with low NF-kB activity under ganciclovir (GCV) treatment. Targeted gene was then identified by using VBIM specific primers. In a preliminary screen, we identified the novel beta-catenin like protein (BCLP) gene as a negative regulator of NF-kB. Overexpression of BCLP led to decreased NF-kB activity by kB reporter assay, while knocking it down had the opposite effect. Furthermore, we found that overexpression of BCLP in HT29 colon cancer cells greatly reduced both the number and the size of colonies that were formed in a soft agar assay, while sh-RNA mediated knockdown resulted in an opposite effect, confirming that BCLP is a tumor suppressor in HT29 cells. Our future experiments aim to further assess the role of BCLP in colon tumor formation in a mouse xenograft model. In summary, by using the novel VBIM technique, we identified BCLP as a novel negative regulator of NF-kB. This discovery could lead to the establishment of BCLP as a potential biomarker and therapeutic target in colon cancer. Citation Format: Rasika Mundade, Tao Lu. VBIM technology identifies beta-catenin-like protein (BCLP) as a novel negative regulator of NF-kB. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5273. doi:10.1158/1538-7445.AM2014-5273
Comparison of 99mTc-MIBI SPECT/18F-FDG PET Imaging and Cardiac Magnetic Resonance Imaging in Patients With Idiopathic Dilated Cardiomyopathy
Authors: Lei Wang, Chaowu Yan, Shihua Zhao, Wei Fang
Journal: Clinical Nuclear Medicine (2012)

The aim of this study is to evaluate the agreement between myocardial F-FDG PET imaging and cardiac magnetic resonance imaging (cMRI) in assessing cardiac function and relationship of cMRI late gadolinium enhancement (cMRI-LGE) and myocardial perfusion/metabolism pattern in patients with idiopathic dilated cardiomyopathy (IDCM).Forty-two consecutive patients diagnosed with IDCM were enrolled. All patients underwent Tc-MIBI SPECT, gated F-FDG PET imaging, and cMRI within 3-7 days. Cardiac function parameters were calculated using PET and cMRI. The segments analysis was performed using a 17-segment model. Patterns of perfusion/metabolism were classified as normal, mismatch, mild-to-moderate match, and severe match, and cMRI-LGE was classified into 3 categories (non-LGE, mid-wall LGE, and transmural LGE).The correlation between gated PET and cMRI was excellent for end-diastolic volume (EDV; r = 0.948, P < 0.001), end-systolic volume (ESV; r = 0.939, P < 0.001), and left ventricular ejection fraction (LVEF; r = 0.685, P < 0.001). EDV and ESV were underestimated, whereas LVEF was slightly overestimated by gated PET in comparison to cMRI. Perfusion/metabolism patterns varied in 3 different categories of non-LGE, mid-wall LGE, and transmural LGE (χ = 14.276, P < 0.001). Also, 71.0% (44/62) segments with mid-wall LGE had normal perfusion/metabolism patterns, and 75.9% (63/83) perfusion/metabolism mismatch segments were shown as non-LGE. The incidence of LGE was significantly higher in segments with severe match than the other 3 segment groups (χ = 112.53, P < 0.001).There is an excellent agreement between gated PET and cMRI in assessment of cardiac function. LGE-cMRI is much more sensitive in detecting moderate fibrosis, while PET could detect more impaired but viable myocardium. Combining the 2 imaging modalities is useful for providing more comprehensive evaluations of myocardial injury in patients with IDCM.
Prevalence of antibody to poliovirus in England and Wales 1984-6.
Authors: P M White, J Green
Journal: BMJ (1986)

Serum from 995 subjects aged 6 months to 99 years was screened at a dilution of 1/8 for neutralising antibodies to poliovirus. Of these samples, 975 (98%) contained antibody to at least one serotype, and 763 (77%) contained antibody to all three, an improvement since previous studies. Children aged 8 to 15, however, had a low prevalence of antibody to poliovirus type 3, with only four (40%) of those aged 12 protected. This finding is possibly due to the waning of antibodies induced by the type 3 component of oral poliovirus vaccine and emphasises the continued importance of a booster dose of vaccine for those leaving school.
Problems in evaluating radiation dose via terrestrial and aquatic pathways.
Authors: B E Vaughan, J K Soldat, R G Schreckhise, E C Watson, D H McKenzie
Journal: Environmental Health Perspectives (1981)

This review is concerned with exposure risk and the environmental pathways models used for predictive assessment of radiation dose. Exposure factors, the adequacy of available data, and the model subcomponents are critically reviewed from the standpoint of absolute error propagation. Although the models are inherently capable of better absolute accuracy, a calculated dose is usually overestimated by from two to six orders of magnitude, in practice. The principal reason for so large an error lies in using "generic" concentration ratios in situations where site specific data are needed. Major opinion of the model makers suggests a number midway between these extremes, with only a small likelihood of ever underestimating the radiation dose. Detailed evaluations are made of source considerations influencing dose (i.e., physical and chemical status of released material); dispersal mechanisms (atmospheric, hydrologic and biotic vector transport); mobilization and uptake mechanisms (i.e., chemical and other factors affecting the biological availability of radioelements); and critical pathways. Examples are shown of confounding in food-chain pathways, due to uncritical application of concentration ratios. Current thoughts of replacing the critical pathways approach to calculating dose with comprehensive model calculations are also shown to be ill-advised, given present limitations in the comprehensive data base. The pathways models may also require improved parametrization, as they are not at present structured adequately to lend themselves to validation. The extremely wide errors associated with predicting exposure stand in striking contrast to the error range associated with the extrapolation of animal effects data to the human being.