tbuckley/cabot-search huggingface dataset:
The Host Response to Adenovirus, Helper-dependent Adenovirus, and Adeno-associated Virus in Mouse Liver
Authors: Anton P McCaffrey, Paul Fawcett, Hiroyuki Nakai, Ramona L McCaffrey, Anja Ehrhardt, Thu-Thao T Pham, Kusum Pandey, Hui Xu, Sally Feuss, Theresa A Storm, Mark A Kay
Journal: Molecular Therapy (2008)

Understanding host responses to viral gene therapy vectors is necessary for the development of safe and efficacious in vivo gene transfer agents. We describe the use of high-density spotted complementary DNA microarrays in monitoring the in vivo host transcriptional responses in mouse liver upon administration of either a "first-generation"adenoviral (Ad) vector, a helper-dependent "gutless" adenoviral (HD) vector, or an adeno-associated viral (AAV) vector containing human factor IX (hFIX) expression cassettes. Since HD and AAV do not contain any viral genes, they allow us to assess the host response to the viral capsid and packaged nonviral DNA in whole animals. Comparison of the host response to Ad and HD helps assess the importance of leaky adenoviral gene expression. While all three vectors induced characteristic temporally sequenced programs of gene expression, the gene expression programs induced by the Ad and HD adenovirus vectors were remarkably similar, including the induction of a prominent type I interferon (IFN)-dependent cluster within 6 hours of administration. In contrast, the AAV-based vector caused far fewer alterations of host-gene expression. Our results indicate that recognition of the Ad capsid or double-stranded DNA (of nonviral origin) in the vector elicits a robust type I IFN response that is, however, not elicited by AAV-derived vector transduction. Understanding host responses to viral gene therapy vectors is necessary for the development of safe and efficacious in vivo gene transfer agents. We describe the use of high-density spotted complementary DNA microarrays in monitoring the in vivo host transcriptional responses in mouse liver upon administration of either a "first-generation"adenoviral (Ad) vector, a helper-dependent "gutless" adenoviral (HD) vector, or an adeno-associated viral (AAV) vector containing human factor IX (hFIX) expression cassettes. Since HD and AAV do not contain any viral genes, they allow us to assess the host response to the viral capsid and packaged nonviral DNA in whole animals. Comparison of the host response to Ad and HD helps assess the importance of leaky adenoviral gene expression. While all three vectors induced characteristic temporally sequenced programs of gene expression, the gene expression programs induced by the Ad and HD adenovirus vectors were remarkably similar, including the induction of a prominent type I interferon (IFN)-dependent cluster within 6 hours of administration. In contrast, the AAV-based vector caused far fewer alterations of host-gene expression. Our results indicate that recognition of the Ad capsid or double-stranded DNA (of nonviral origin) in the vector elicits a robust type I IFN response that is, however, not elicited by AAV-derived vector transduction.
Validation of a field test for the non-invasive determination of badminton specific aerobic performance
Authors: M Wonisch, P Hofmann, G Schwaberger, S P von Duvillard, W Klein
Journal: British Journal of Sports Medicine (2003)

To develop a badminton specific test to determine on court aerobic and anaerobic performance.The test was evaluated by using a lactate steady state test. Seventeen male competitive badminton players (mean (SD) age 26 (8) years, weight 74 (10) kg, height 179 (7) cm) performed an incremental field test on the badminton court to assess the heart rate turn point (HRTP) and the individual physical working capacity (PWC(i)) at 90% of measured maximal heart rate (HR(max)). All subjects performed a 20 minute steady state test at a workload just below the PWC(i).Significant correlations (p<0.05) for Pearson's product moment coefficient were found between the two methods for HR (r = 0.78) and velocity (r = 0.93). The HR at the PWC(i) (176 (5.5) beats/min) was significantly lower than the HRTP (179 (5.5) beats/min), but no significant difference was found for velocity (1.44 (0.3) m/s, 1.38 (0.4) m/s). The constant exercise test showed steady state conditions for both HR (175 (9) beats/min) and blood lactate concentration (3.1 (1.2) mmol/l).The data indicate that a valid determination of specific aerobic and anaerobic exercise performance for the sport of badminton is possible without HRTP determination.
Primary pulmonary lymphoma
Authors: J. Cadranel, M. Wislez, M. Antoine
Journal: European Respiratory Journal (2002)

Three distinct entities are now covered by the definition of primary pulmonary clonal lymphoid proliferation. The aim of this review is to describe the pathophysiological, diagnostic, prognostic and therapeutic aspects of these three entities. Low-grade pulmonary B-cell lymphoma is the most frequent form of primary pulmonary clonal lymphoid proliferation. It arises from mucosa-associated lymphoid tissue. It is usually indolent and appears in the form of a chronic alveolar opacity. The prognosis is excellent, but treatment is controversial (simple monitoring, surgery or single-agent chemotherapy). High-grade pulmonary B-cell lymphoma is far rarer and usually occurs in individuals with an underlying disorder ( e.g. immunodeficiency). The prognosis is poor and therapeutic options depend on the underlying disorder. The inclusion of lymphomatoid granulomatosis in the definition of primary pulmonary lymphomas is controversial. The clonal nature of the proliferation is very rarely demonstrated and extrapulmonary involvement is frequent (upper airways, skin, kidneys, central nervous system, etc. ). The prognosis is extremely variable, with some authors reporting complete remission with steroids and cyclophosphamide and others reporting failure of combination chemotherapy.
Acute and long-term effects of tissue culture on contractile reactivity in renal arteries of the rat.
Authors: J G De Mey, M P Uitendaal, H C Boonen, M J Vrijdag, M J Daemen, H A Struyker-Boudier
Journal: Circulation Research (1989)

To evaluate long-term effects of contractile and mitogenic stimuli on the contractile reactivity of arterial smooth muscle, we measured the incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd) and mechanical responses in arterial segments that had been maintained in tissue culture. The experiments were performed on renal arteries that had been isolated from adult rats, chemically sympathectomized, mechanically denuded from endothelium and mounted under distension. Exposure of arterial segments for up to 3 weeks to culture medium supplemented with fetal calf serum resulted in the following consecutive changes: a strong acute contraction, selective pharmacological changes that included decreased contractile responses to phenylephrine and vasopressin and increased relaxing responses to isoproterenol, increased incorporation of BrdUrd, a progressive fall in contractile responses to all vasoconstrictor stimuli, and an increase in excitability. Serum-free medium resulted in a much smaller acute arterial contraction, induced less incorporation of BrdUrd, accelerated the occurrence of hyperexcitability, but did not affect early pharmacological changes or the subsequent fall in overall arterial contractility with tissue culture. Dialysis of the serum or addition of ketanserin abolished the contractile effect of serum but did not affect the incorporation of BrdUrd or the loss of contractility with tissue culture. Addition of serotonin to serum-free culture medium mimicked the contractile response to serum but not the stimulation of BrdUrd incorporation. These data indicate that tissue culture alters the properties of the arterial wall, that contraction does not underlie the proliferative response of arterial smooth muscle to serum-derived mitogens in vitro, and that stimulation of DNA synthesis does in itself not lead to selective changes in arterial contractility.
A study of chemical light screening agents
Authors: T.M. MACLEOD, W. FRAIN-BELL
Journal: British Journal of Dermatology (1975)

In a group of 104 non‐photosensitive subjects and seventy‐eight suffering from a variety of photodermatoses, the most effective protective preparation against irradiation by short UV sunburn wavelengths (<320 nm) was found to be a mixture of 5% para‐aminobenzoic acid and 2.5% of the ester amyl dimethylaminobenzoate in 70% ethanol with para‐aminobenzoic acid being usually more effective than the ester, and mexenone the least effective individually. The protective capacity was found to be reduced by showering but not by exercise. The addition of glycerol to the formulations did not affect their protective capacity although the addition of propylene glycol did increase the protection obtained.
Risks of Overweight and Abdominal Obesity at Age 16 Years Associated With Prenatal Exposures to Maternal Prepregnancy Overweight and Gestational Diabetes Mellitus
Authors: Jatta Pirkola, Anneli Pouta, Aini Bloigu, Anna-Liisa Hartikainen, Jaana Laitinen, Marjo-Riitta Järvelin, Marja Vääräsmäki
Journal: Diabetes Care (2010)

The associations of prenatal exposures to maternal prepregnancy overweight and gestational diabetes mellitus (GDM) with offspring overweight are controversial. Research estimating risk for offspring overweight due to these exposures, separately and concomitantly, is limited.Prevalence of overweight and abdominal obesity at age 16 years and odds ratios (ORs) for prenatal exposures to maternal prepregnancy overweight and GDM were estimated in participants of the prospective longitudinal Northern Finland Birth Cohort of 1986 (N = 4,168).The prevalence and estimates of risk for overweight and abdominal obesity were highest in those exposed to both maternal prepregnancy overweight and GDM (overweight prevalence 40% [OR 4.05], abdominal obesity prevalence 25.7% [3.82]). Even in offspring of mothers with a normal oral glucose tolerance test during pregnancy, maternal prepregnancy overweight is associated with increased risk for these outcomes (overweight prevalence 27.9% [2.56], abdominal obesity prevalence 19.5% [2.60]). In offspring of women with prepregnancy normal weight, the prevalence or risks of the outcomes were not increased by prenatal exposure to GDM. These estimates of risk were adjusted for parental prepregnancy smoking, paternal overweight, and offspring sex and size at birth.Maternal prepregnancy overweight is an independent risk factor for offspring overweight and abdominal obesity at age 16 years. The risks are highest in offspring with concomitant prenatal exposure to maternal prepregnancy overweight and GDM, whereas the risks associated with GDM are only small.
Predictive Value of Symptoms for Ovarian Cancer: Comparison of Symptoms Reported by Questionnaire, Interview, and General Practitioner Notes
Authors: Anita W. W. Lim, David Mesher, Aleksandra Gentry-Maharaj, Nyaladzi Balogun, Ian Jacobs, Usha Menon, Peter Sasieni
Journal: JNCI Journal of the National Cancer Institute (2012)

Because of the poor survival outcomes associated with advanced ovarian cancer, early detection strategies are needed. Although several symptom indices have been described, their relationship with the potential lead time has been poorly documented.Women aged 50-79 years who had newly diagnosed ovarian cancer (n = 194) and control subjects (n = 268) who attended ovarian cancer screening clinics were included in the analysis. Symptoms and their onset dates were obtained from three sources: a questionnaire (191 case patients and 268 control subjects), telephone interview (111 case patients and 125 control subjects), and general practitioner (GP) notes (171 case patients and 227 control subjects). Data from questionnaires and GP notes were used to derive two new symptom indices (Index 1 and Index 2). Sensitivity and specificity for these new indices and the previously reported Goff index were calculated for the periods of 0-11 and 3-14 months before diagnosis for all three data sources.For each data source and period, the two new symptom indices derived from questionnaire and GP notes were similar both qualitatively (symptoms included) and quantitatively (sensitivity and specificity) to the Goff index. When symptoms that started within 3 months before diagnosis were excluded, sensitivity was decreased for all indices and all data sources (eg, for telephone interviews, sensitivity for the period 0-11 vs 3-14 months before diagnosis: for Index 1 = 91.0% vs 69.4%, difference = 21.6%, 95% confidence interval [CI] = 13.6% to 29.7%; for Index 2 = 91.0% vs 60.4%, difference = 30.6%, 95% CI = 21.7% to 39.6%; and for the Goff index = 75.7% vs 51.4%, difference = 24.3%, 95% CI = 16.0% to 32.7%). Also, the specificity of all indices was consistently decreased for telephone interviews compared with questionnaires and GP notes (eg, 1 - specificity for the period of 3-14 months before diagnosis for telephone interviews vs questionnaires: for Index 1 = 19.2% vs 10.4%, difference = 8.8%, 95% CI = 1.0% to 16.6%; for Index 2 = 14.4% vs 6.7%, difference = 7.7%, 95% CI = 0.9% to 14.5%; and for the Goff Index = 7.2% vs 1.5%, difference = 5.7%, 95% CI = 0.9% to 10.5%).Previous estimates of index performance have been overly optimistic because they did not take into account the time required to make a diagnosis on the basis of testing in response to symptoms. In addition, the specificity of a symptom index is lower when based on a telephone interview vs questionnaire or GP notes. Thus, the clinical utility of a symptom index depends on precisely how it is used and how index-positive women are managed.
Extracts from an Essay on Pericarditis
Authors: M. M. de Bartolome
Journal: BMJ (1847)

ON PERICARDITIS.the pbenomenL which exemplify, and appear to me -satisfactorily to prove, the existence and operation of a morphological law in animal textures, let me recapitu.-late the points Ohich are settled and established with regard to plants:-1.Regular metamorphosis is the process by which 'the type, texture, and form, established by Nature for.*the species, are perfected, and handed down from parent
Ca <sup>2+</sup> -Calmodulin–Dependent Protein Kinase Phosphorylation of Ryanodine Receptor May Contribute to the β-Adrenergic Regulation of Myocardial Contractility Independently of Increases in Heart Rate
Authors: Alicia Mattiazzi, Leticia Vittone, Cecilia Mundiña-Weilenmann
Journal: Circulation Research (2008)
Breast Cancer Stem Cells Are Regulated by Mesenchymal Stem Cells through Cytokine Networks
Authors: Suling Liu, Christophe Ginestier, Sing J. Ou, Shawn G. Clouthier, Shivani H. Patel, Florence Monville, Hasan Korkaya, Amber Heath, Julie Dutcher, Celina G. Kleer, Younghun Jung, Gabriela Dontu, Russell Taichman, Max S. Wicha
Journal: Cancer Research (2011)

Abstract We have used in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSC) and bone marrow–derived mesenchymal stem cells (MSC). We show that both of these cell populations are organized in a cellular hierarchy in which primitive aldehyde dehydrogenase expressing mesenchymal cells regulate breast CSCs through cytokine loops involving IL6 and CXCL7. In NOD/SCID mice, labeled MSCs introduced into the tibia traffic to sites of growing breast tumor xenografts where they accelerated tumor growth by increasing the breast CSC population. With immunochemistry, we identified MSC–CSC niches in these tumor xenografts as well as in frozen sections from primary human breast cancers. Bone marrow–derived MSCs may accelerate human breast tumor growth by generating cytokine networks that regulate the CSC population. Cancer Res; 71(2); 614–24. ©2011 AACR.
ZONAB Promotes Proliferation and Represses Differentiation of Proximal Tubule Epithelial Cells
Authors: Wânia R. Lima, Kleber S. Parreira, Olivier Devuyst, Adrian Caplanusi, Francisca N′Kuli, Benoit Marien, Patrick Van Der Smissen, Pedro M.S. Alves, Pierre Verroust, Erik I. Christensen, Fabiola Terzi, Karl Matter, Maria S. Balda, Christophe E. Pierreux, Pierre J. Courtoy
Journal: Journal of the American Society of Nephrology (2010)

Epithelial polarization modulates gene expression. The transcription factor zonula occludens 1 (ZO-1)-associated nucleic acid binding protein (ZONAB) can shuttle between tight junctions and nuclei, promoting cell proliferation and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA), but whether it also represses epithelial differentiation is unknown. Here, during mouse kidney ontogeny and polarization of proximal tubular cells (OK cells), ZONAB and PCNA levels decreased in parallel and inversely correlated with increasing apical differentiation, reflected by expression of megalin/cubilin, maturation of the brush border, and extension of the primary cilium. Conversely, ZONAB reexpression and loss of apical differentiation markers provided a signature for renal clear cell carcinoma. In confluent OK cells, ZONAB overexpression increased proliferation and PCNA while repressing megalin/cubilin expression and impairing differentiation of the brush border and primary cilium. Reporter and chromatin immunoprecipitation assays demonstrated that megalin and cubilin are ZONAB target genes. Sparsely plated OK cells formed small islands composed of distinct populations: Cells on the periphery, which lacked external tight junctions, strongly expressed nuclear ZONAB, proliferated, and failed to differentiate; central cells, surrounded by continuous junctions, lost nuclear ZONAB, stopped proliferating, and engaged in apical differentiation. Taken together, these data suggest that ZONAB is an important component of the mechanisms that sense epithelial density and participates in the complex transcriptional networks that regulate the switch between proliferation and differentiation.
The Histone Deacetylase Inhibitor LBH589 Is a Potent Antimyeloma Agent that Overcomes Drug Resistance
Authors: Patricia Maiso, Xonia Carvajal-Vergara, Enrique M. Ocio, Ricardo López-Pérez, Gema Mateo, Norma Gutiérrez, Peter Atadja, Atanasio Pandiella, Jesús F. San Miguel
Journal: Cancer Research (2006)

Multiple myeloma represents an incurable disease, for which development of new therapies is required. Here, we report the effect on myeloma cells of LBH589, a new hydroxamic acid-derived histone deacetylase inhibitor. LBH589 was a potent antimyeloma agent (IC(50) < 40 nmol/L) on both cell lines and fresh cells from multiple myeloma patients, including cells resistant to conventional chemotherapeutic agents. In addition, LBH589 potentiated the action of drugs, such as bortezomib, dexamethasone, or melphalan. Using gene array, quantitative PCR, and Western analyses, we observed that LBH589 affected a large number of genes involved in cell cycle and cell death pathways. LBH589 blocked cell cycle progression, and this was accompanied by p21, p53, and p57 up-regulation. LBH589 induced cell death through an increase in the mitochondrial outer membrane permeability. LBH589 favored apoptosome formation by inducing cytochrome c release, Apaf-1 up-regulation, and caspase-9 cleavage. In addition, LBH589 stimulated a caspase-independent pathway through the release of AIF from the mitochondria. LBH589 down-regulated Bcl-2 and particularly Bcl-X. Moreover, overexpression of Bcl-X in multiple myeloma cells prevented LBH589-induced cell death. All these data indicate that LBH589 could be a useful drug for the treatment of multiple myeloma patients.
P47 Outcomes of static vs continuous rolling community pulmonary rehabilitation (PR) programmes
Authors: J. Tomkinson, M. Rossdale
Journal: Thorax (2010)

<h3>Introduction &amp; objectives</h3> Previous research in PR has focussed on duration and location of courses, and models of exercise therapy. In order to meet a commissioning adherence target for 2009–2010, the Bristol community PR team modified stand alone static programmes (SP) (6 week) seeing 150 people per year to add in a continuous rolling programme (CRP) (2–4 new patients start every week attending 6 weeks) with the aim of improving adherence to programmes. The objective of this study was to examine if the outcomes of a CRP were as effective as the SP. <h3>Method</h3> Retrospective analysis of outcome data for year 2009–2010 for improvement in 6 min walk test (m), change in Chronic Respiratory Disease Questionnaire (CRDQ), and attendance. Patients were offered a choice of programme at their initial clinic assessment. <h3>Results</h3> Results for the two groups are shown in Abstract P47 Table 1. There were no significant differences between groups at baseline. The CRP had 55 (174%) more patients complete the programme throughout the year. There was no significant difference between groups for improvement in walking distance, attendance or CRDQ-D, CRDQ-F or CRDQ-EF. There was a significant improvement in the CRDQ-M in the CRP group. <h3>Conclusion</h3> This audit shows that the outcomes for a CRP are as good as SP and can be used as an effective method of delivering PR. Both groups require the same amount of staff time; however the CRP saw more patients and had more completers. This may be as cohorts of COPD patients often lose members which can reduce SP9s by up to 33%. Within a CRP as patients drop out, new patients can be started keeping the cohort at a set level, thus allowing more patients to be seen. There appears to be a positive effect on CRDQ mastery with patients scoring significantly higher on this in the CRP. This may be an effect of patients who have attended for a while taking on the role as ‘experienced buddy’ helping the naive patient (Heisler 2009), however further research to investigate this is warranted.
The Major Reverse Transcriptase–Incompetent Splice Variant of the Human Telomerase Protein Inhibits Telomerase Activity but Protects from Apoptosis
Authors: Imke Listerman, Jie Sun, Francesca S. Gazzaniga, Jason L. Lukas, Elizabeth H. Blackburn
Journal: Cancer Research (2013)

Abstract Human telomerase reverse transcriptase (hTERT; the catalytic protein subunit of telomerase) is subjected to numerous alternative splicing events, but the regulation and function of these splice variants is obscure. Full-length hTERT includes conserved domains that encode reverse transcriptase activity, RNA binding, and other functions. The major splice variant termed α+β− or β-deletion is highly expressed in stem and cancer cells, where it codes for a truncated protein lacking most of the reverse transcriptase domain but retaining the known RNA-binding motifs. In a breast cancer cell panel, we found that β-deletion was the hTERT transcript that was most highly expressed. Splicing of this transcript was controlled by the splice regulators SRSF11, HNRNPH2, and HNRNPL, and the β-deletion transcript variant was associated with polyribosomes in cells. When ectopically overexpressed, β-deletion protein competed for binding to telomerase RNA (hTR/TERC), thereby inhibiting endogenous telomerase activity. Overexpressed β-deletion protein localized to the nucleus and mitochondria and protected breast cancer cells from cisplatin-induced apoptosis. Our results reveal that a major hTERT splice variant can confer a growth advantage to cancer cells independent of telomere maintenance, suggesting that hTERT makes multiple contributions to cancer pathophysiology. Cancer Res; 73(9); 2817–28. ©2013 AACR.