tbuckley/cabot-search huggingface dataset:
Determinants of Arterial Wall Remodeling During Lipid-Lowering Therapy
Authors: Paul Schoenhagen, E. Murat Tuzcu, Carolyn Apperson-Hansen, Chaohui Wang, Kathy Wolski, Songhua Lin, Ilke Sipahi, Stephen J. Nicholls, William A. Magyar, Aaron Loyd, Tammy Churchill, Tim Crowe, Steven E. Nissen
Journal: Circulation (2006)

Coronary plaque progression and instability are associated with expansive remodeling of the arterial wall. However, the remodeling response during plaque-stabilizing therapy and its relationship to markers of lipid metabolism and inflammation are incompletely understood.Serial intravascular ultrasound (IVUS) data from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial were obtained during 18 months of intensive versus moderate lipid-lowering therapy. In a subgroup of 210 patients, focal coronary lesions with mild luminal narrowing were identified. Lumen area, external elastic membrane (EEM) area, and plaque area were determined at the lesion and proximal reference sites at baseline and during follow-up. The remodeling ratio (RR) was calculated by dividing the lesion EEM area by the reference EEM area. The relationship between the change in remodeling, change in plaque area, lipid profile, and inflammatory markers was examined. At the lesion site, a progression in plaque area (8.9+/-25.7%) and a decrease in the RR (-3.0+/-11.2%) occurred during follow-up. In multivariable analyses, the percentage change in plaque area (P<0.0001), baseline RR (P<0.0001), baseline lesion lumen area (0.019), logarithmic value of the change in high-sensitivity C-reactive protein (P=0.027), and hypertension at baseline (P=0.014) showed a significant, direct relation with the RR at follow-up. Lesion location in the right coronary artery (P=0.006), percentage change in triglyceride levels (P=0.049), and age (P=0.037) demonstrated a significant, inverse relation with the RR at follow-up. Changes in LDL cholesterol, HDL cholesterol, and treatment group demonstrated no significant associations.Constrictive remodeling of the arterial wall was observed during plaque-stabilizing therapy with statin medications and appears related to their antiinflammatory effects.
Phenotypic heterogeneity of melanoma. Relation to the differentiation program of melanoma cells.
Authors: A N Houghton, F X Real, L J Davis, C Cordon-Cardo, L J Old
Journal: The Journal of Experimental Medicine (1987)

Phenotypic heterogeneity is a characteristic feature of tumor lesions in patients with melanoma. Variability can be observed in cell morphology, pigmentation, and antigen expression. To test whether phenotypic heterogeneity could be the result of events regulated during cell differentiation, we evaluated the expression of a panel of differentiation traits on melanoma cells. Metastatic melanoma lesions from two patients, designated FD and AP, were examined histologically and found to contain mixed populations of cells. Established melanoma cell lines derived from each of these lesions were subcloned at early passage in culture (passages 7 and 8) to create a panel of clones derived from each tumor. There was heterogeneity in the expression of differentiation-related traits in clones, corresponding to distinct phenotypes observed within the original tumors. Clones from patient FD corresponded to early to intermediate stages of melanocyte differentiation, and clones from patient AP ranged from intermediate to late stages. The influence of cholera toxin and PMA on differentiation of parental cultures and subclone was studied. Results of induction studies demonstrated a number of features of differentiation of melanoma cells: regulation of differentiation traits is coordinated as a program of traits expressed sequentially at specific stages; early traits, such as the epidermal growth factor receptor and the melanoma chondroitin sulfate proteoglycan antigen, are downregulated as melanoma cells differentiate, whereas late markers, including melanin, tyrosinase activity, and antigens expressed in mature melanosomes, are upregulated; Ia (class II major histocompatibility) antigens are characteristically expressed on melanomas corresponding to early or intermediate stages of differentiation and are regulated as part of the differentiation program; minimal changes in stage of differentiation were observed during induction of parental cultures with either cholera toxin or PMA, whereas definite shifts in differentiation could be induced in selected cloned subpopulations. We conclude that melanoma cells are not frozen at a specific stage of differentiation, but rather are capable of differentiating when exposed to appropriate signals. Diversity in the differentiation state of melanoma cells can account for much of the phenotypic heterogeneity observed in melanoma lesions.
Antigraft Antibody-Mediated Expression of Metalloproteinases on Endothelial Cells
Authors: Gwénola Boulday, Stéphanie Coupel, Flora Coulon, Jean-Paul Soulillou, Béatrice Charreau
Journal: Circulation Research (2001)

Endothelial cell (EC) interaction with antigraft antibodies (Abs) mediates EC injury and activation involved in vascular graft rejection. The aim of this study was to identify EC genes regulated in response to antigraft Ab binding that contribute to the endothelium alterations implicated in graft rejection or survival. By means of RNA differential display, 13 cDNA fragments corresponding to genes differentially expressed in ECs incubated with antigraft Abs were identified. Among these cDNAs were found the tissue inhibitor of metalloproteinase-1 (TIMP-1) and a desintegrin and metalloproteinase (ADAM-10). We demonstrated that TIMP-1 and ADAM-10 mRNA and protein expression was rapidly upregulated in ECs in response to antigraft Ab binding. Our data showed that TIMP-1 was upregulated in response to human IgG but not IgM and anti-galactosyl (Gal) alpha1-3Gal human xenogeneic Abs. In contrast, upregulation of ADAM-10 in ECs was shown to be mostly mediated by anti-Galalpha1-3Gal IgM Abs. Specific effects of human IgG and IgM xenogeneic Abs on endothelial transcripts indicate that different isotypes and specificities of Abs may mediate different EC changes. Our results suggest that interaction of ECs with antigraft Abs, according to their specificity, selectively induces synthesis and release of metalloproteinases and inhibitors, controlling proteolytic processes and immunological events that respectively contribute to graft rejection or survival.
The inflammatory response to high doses of terbutaline during an acute exercise bout in patients with severe COPD
Authors: Sebastian Lund Karlsson, Morten Hostrup, Anders Kalsen, Nina Godtfredsen, Vibeke Backer
Journal: European Respiratory Journal (2013)

Introduction   Chronic obstructive pulmonary disease (COPD) is an inflammatory respiratory disease caused by noxious gases. New studies have reported a sub-group of patients with elevated levels of inflammatory biomarkers. Still, it is unknown how high doses of inhaled terbutaline influence the inflammatory response after strenuous exercise in patients with COPD. The scope of this study was to clarify how terbutaline affects the systemic inflammatory response.   Methods   Ten patient with severe COPD, FEV1   Results   IL-6 and IL-8 rose significantly (p   Conclusion   High doses of inhaled terbutaline increase plasma IL-6 in patients with severe COPD during an acute exercise bout compared to placebo.
Health-related quality of life in patients surviving non-small cell lung cancer
Authors: J. P. C. Grutters, M. A. Joore, E. M. Wiegman, J. A. Langendijk, D. de Ruysscher, M. Hochstenbag, A. Botterweck, P. Lambin, M. Pijls-Johannesma
Journal: Thorax (2010)

<h3>Background and aims</h3> The EuroQol 5D (EQ-5D) is a standardised instrument for measuring health-related quality of life (HRQoL). It provides a utility score for health, and a self-rating of HRQoL (EQ-VAS). In this study, the EQ-5D was used to assess HRQoL in survivors of non-small cell lung cancer (NSCLC). The influence of tumour stage, adverse events, initial treatment and presence of recurrence was examined. <h3>Methods</h3> Patients treated for NSCLC were sent a questionnaire, consisting of the EQ-5D, EQ-VAS and questions regarding adverse events. Tumour stage, date and type of initial treatment, and presence of recurrence were derived from patient files once patients had completed the questionnaire and informed consent form. Influencing factors were examined by exploring subgroups and using multiple regression analysis. <h3>Results</h3> Of the 374 patients contacted, 260 (70%) returned a completed questionnaire. The EQ-VAS generated an average self-rated health of 69 (SD 18). The mean utility score was 0.74 (SD 0.27). Respondents with severe adverse events (dyspnoea grade ≥3) had statistically significantly lower utility scores than respondents without severe adverse events (median 0.52 vs 0.81; p &lt;0.001). Subgroups based on a patient9s initial treatment modality revealed statistically significantly different utility scores (p=0.010). <h3>Conclusion</h3> The results of the present study provide original data on HRQoL during survival of NSCLC. Adverse events were found to have a considerable impact on HRQoL. This stresses the need to search for treatment modalities that not only improve survival, but also reduce adverse events.
Pulsatile Cardiac Tissue Grafts Using a Novel Three-Dimensional Cell Sheet Manipulation Technique Functionally Integrates With the Host Heart, In Vivo
Authors: Akira Furuta, Shunichiro Miyoshi, Yuji Itabashi, Tatsuya Shimizu, Shinichiro Kira, Keiko Hayakawa, Nobuhiro Nishiyama, Kojiro Tanimoto, Yoko Hagiwara, Toshiaki Satoh, Keiichi Fukuda, Teruo Okano, Satoshi Ogawa
Journal: Circulation Research (2006)

We devised a method of fabricating easily transplantable scaffoldless 3D heart tissue, made with a novel cell-sheet (CS) technology from cultured cardiomyocytes using a fibrin polymer coated dish. In the present study, we tested in vivo electrical communication which is essential for improving heart function between the host heart and the grafted CS. The epicardial surface of the ventricle of an anesthetized open-chest nude rat was ablated by applying a heated metal. Bilayered CS was obtained from neonatal rat primary culture. CS was transplanted onto the injured myocardial surface (sMI) (sMI+sheet group). The rats were allowed to recover for 1 to 4 weeks, to stabilize the grafts. Action potentials (APs) from the excised perfused heart were monitored by the fluorescence signal of di-4ANEPPS with a high speed charge-coupled device camera. The APs were observed under epicardial pacing of the host heart or the CS grafts. The pacing threshold of the current output was measured in the sMI+sheet group and in the nongrafted sMI group at the center of the sMI and in the normal zone (Nz). Bidirectional AP propagation between the sMI and Nz was observed in the sMI+sheet group (n=14), but was blocked at the marginal area of the sMI in the sMI group (n=9). The ratio of the pacing threshold (sMI/Nz) was significantly lower in the sMI+sheet than in the sMI group (3.0±0.7, 19.0±6.1 respectively P &lt;0.05). There were neither spontaneous nor pacing-induced arrhythmias in these two groups. Bidirectional smooth AP propagation between the host heart and the grafted CS was observed. This finding suggested functional integration of this CS graft with the host heart without serious arrhythmia.
Longitudinal Study of Depressive Symptoms and Progression of Insulin Resistance in Youth at Risk for Adult Obesity
Authors: Lauren B. Shomaker, Marian Tanofsky-Kraff, Elizabeth A. Stern, Rachel Miller, Jaclyn M. Zocca, Sara E. Field, Susan Z. Yanovski, Van S. Hubbard, Jack A. Yanovski
Journal: Diabetes Care (2011)

OBJECTIVE The purpose of this study was to determine whether having childhood depressive symptoms is a risk factor that prospectively predicts impairment in glucose homeostasis. RESEARCH DESIGN AND METHODS A non–treatment-seeking sample of 115 children (aged 5–13 years), oversampled for being at risk for adult obesity, was assessed at baseline and again ~6 years later. Children self-reported depressive symptoms using the Children’s Depression Inventory at baseline. Insulin resistance was assessed at baseline and follow-up with the homeostasis model assessment of insulin resistance index (HOMA-IR). RESULTS Children’s depressive symptoms were a significant predictor of follow-up HOMA-IR, fasting insulin, and fasting glucose in models accounting for baseline HOMA-IR, insulin, or glucose values; sex; race; baseline age; baseline BMI; change in BMI at follow-up; family history of type 2 diabetes; and time in the study (P &amp;lt; 0.01). CONCLUSIONS In this study, depressive symptomatology at baseline predicted the progression of insulin resistance during child and adolescent development independent of changes in BMI. Research is needed to determine whether early intervention to decrease elevated depressive symptoms in youth ameliorates later development of insulin resistance and lessens the risk of type 2 diabetes.
Cocarcinogenic Effects of n-Alkanes and Ultraviolet Light on Mice2
Authors: Eula Bingham, Peter J. Nord
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Cocarcinogenic Effects of n-Alkanes and Ultraviolet Light on Mice Get access Eula Bingham, Eula Bingham Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter J. Nord Peter J. Nord Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 4, April 1977, Pages 1099–1101, https://doi.org/10.1093/jnci/58.4.1099 Published: 01 April 1977 Article history Received: 01 August 1975 Revision received: 23 September 1976 Accepted: 14 October 1976 Published: 01 April 1977
E2F1 Induces Tumor Cell Survival via Nuclear Factor-κB–Dependent Induction of EGR1 Transcription in Prostate Cancer Cells
Authors: Chaogu Zheng, Zijia Ren, Hetian Wang, Weici Zhang, Dhananjaya V. Kalvakolanu, Zhigang Tian, Weihua Xiao
Journal: Cancer Research (2009)

Transcription factor E2F1 has been implicated in both apoptosis-promoting and apoptosis-suppressing effects. However, factors that mediate its antiapoptotic effects are still not identified. Using prostate tumor-derived cell lines, we showed here that E2F1 activated the expression of transcription factor EGR1 for promoting cell survival. E2F1 up-regulated the production of EGR1-induced growth factors, epidermal growth factor, platelet-derived growth factor, and insulin-like growth factor II, which in turn activated the phosphoinositide-3-kinase/Akt pathway to resist drug-induced apoptosis. Moreover, E2F1 directly induced the transcription of the Egr1 gene using the kappaB site located in its proximal promoter. E2F1 physically interacted with the RelA subunit of nuclear factor-kappaB and modulated its transactivity to fully activate EGR1 transcription. Together, these studies uncovered a novel mechanism for E2F1-induced suppression of apoptosis in prostate cancer. [Cancer Res 2009;69(6):2324-31].
Impact of Azacytidine on the Quality of Life of Patients With Myelodysplastic Syndrome Treated in a Randomized Phase III Trial: A Cancer and Leukemia Group B Study
Authors: Alice B. Kornblith, James E. Herndon, Lewis R. Silverman, Erin P. Demakos, Rosalie Odchimar-Reissig, James F. Holland, Bayard L. Powell, Carlos DeCastro, John Ellerton, Richard A. Larson, Charles A. Schiffer, Jimmie C. Holland
Journal: Journal of Clinical Oncology (2002)

The impact of azacytidine (Aza C) on the quality of life of 191 patients with myelodysplastic syndrome was assessed in a phase III Cancer and Leukemia Group B trial (9221).One hundred ninety-one patients (mean age, 67.5 years; 69% male) were randomized to receive either Aza C (75 mg/m(2) subcutaneous for 7 days every 4 weeks) or supportive care, with supportive care patients crossing over to Aza C upon disease progression. Quality of life was assessed by centrally conducted telephone interviews at baseline and days 50, 106, and 182. Overall quality of life, psychological state, and social functioning were assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and the Mental Health Inventory (MHI).Patients on the Aza C arm experienced significantly greater improvement in fatigue (EORTC, P =.001), dyspnea (EORTC, P =.0014), physical functioning (EORTC, P =.0002), positive affect (MHI, P =.0077), and psychological distress (MHI, P =.015) over the course of the study period than those in the supportive care arm. Particularly striking were improvements in fatigue and psychological state (MHI) in patients treated with Aza C compared with those receiving supportive care for patients who remained on study through at least day 106, corresponding to four cycles of Aza C. Significant differences between the two groups in quality of life were maintained even after controlling for the number of RBC transfusions.Improved quality of life for patients treated with Aza C coupled with significantly greater treatment response and delayed time to transformation to acute myeloid leukemia or death compared with patients on supportive care (P <.001) establishes Aza C as an important treatment option for myelodysplastic syndrome.
THOMAS EDGE ANDERSON
Authors: R.A. Main
Journal: British Journal of Dermatology (1974)

Journal Article THOMAS EDGE ANDERSON Get access R.A. Main R.A. Main Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 90, Issue 3, 1 March 1974, Pages 358–359, https://doi.org/10.1111/j.1365-2133.1974.tb06416.x Published: 01 March 1974
Protection from angiotensin II–mediated vasculotoxic and hypertensive response in mice lacking PI3Kγ
Authors: Carmine Vecchione, Enrico Patrucco, Gennaro Marino, Laura Barberis, Roberta Poulet, Alessandra Aretini, Angelo Maffei, Maria Teresa Gentile, Marianna Storto, Ornella Azzolino, Mara Brancaccio, Gian Luca Colussi, Umberto Bettarini, Fiorella Altruda, Lorenzo Silengo, Guido Tarone, Mathias P. Wymann, Emilio Hirsch, Giuseppe Lembo
Journal: The Journal of Experimental Medicine (2005)

Hypertension affects nearly 20% of the population in Western countries and strongly increases the risk for cardiovascular diseases. In the pathogenesis of hypertension, the vasoactive peptide of the renin-angiotensin system, angiotensin II and its G protein–coupled receptors (GPCRs), play a crucial role by eliciting reactive oxygen species (ROS) and mediating vessel contractility. Here we show that mice lacking the GPCR-activated phosphoinositide 3-kinase (PI3K)γ are protected from hypertension that is induced by administration of angiotensin II in vivo. PI3Kγ was found to play a role in angiotensin II–evoked smooth muscle contraction in two crucial, distinct signaling pathways. In response to angiotensin II, PI3Kγ was required for the activation of Rac and the subsequent triggering of ROS production. Conversely, PI3Kγ was necessary to activate protein kinase B/Akt, which, in turn, enhanced L-type Ca2+ channel–mediated extracellular Ca2+ entry. These data indicate that PI3Kγ is a key transducer of the intracellular signals that are evoked by angiotensin II and suggest that blocking PI3Kγ function might be exploited to improve therapeutic intervention on hypertension.
Efficacy of Metabolic and Psychological Screening for Mood Disorders Among Children With Type 1 Diabetes
Authors: Agnieszka Butwicka, Wojciech Fendler, Adam Zalepa, Agnieszka Szadkowska, Beata Mianowska, Agnieszka Gmitrowicz, Wojciech Młynarski
Journal: Diabetes Care (2012)

To compare the diagnostic accuracy and time expenditure of screening models based on glycated hemoglobin (HbA(1c)) level and psychometric measures for mood disorder (MD) among children with type 1 diabetes.With semistructured clinical interviews (Schedule for Affective Disorders and Schizophrenia for Children-Present and Lifetime version, 120 min/patient) as a reference for diagnosing MD, including major depressive disorder (MDD), we tested 163 subjects, aged 8 to 18 years, with type 1 diabetes. We evaluated four screening approaches: 1) Children's Depression Inventory (CDI) at 30 min/patient, 2) HbA(1c) level, 3) HbA(1c) level plus CDI, and 4) HbA(1c) level plus Children's Depression Rating Scale (CDRS) at 40 min/patient. These tests were conducted with all participants, and the total time expenditure for all four approaches was calculated as the total time needed to implement successfully the screening for MD or MDD in the center.HbA(1c) performed on par with individual psychometric tests in diagnosing MD or MDD. The HbA(1c) plus CDRS model was the best screening procedure for both MD and MDD, with diagnostic thresholds for HbA(1c) established at 8.7% and 9.0%, respectively. Cutoff points for CDRS assessed after filtering by HbA(1c) were 26 (MD) and 30 (MDD) points. Center-wide application of this procedure would result in an 83% reduction of the examination time necessary for the psychiatrist for MD screening and a 91% reduction for MDD screening, as compared with standard screening with CDI.Use of HbA(1c) level followed by CDRS is a time-efficient procedure to screen for MD in children with type 1 diabetes.
Is contemporary grandparental care an evolutionary mismatch?
Authors: Harald A. Euler
Journal: Behavioral and Brain Sciences (2010)

Abstract In order to evaluate the impact of contemporary grandparenting, the view should not be restricted to developmental achievement effects in grandchildren. Both child happiness and grandparent happiness are high-ranking goals with implications for public policy. The beneficial impact of grandparenting for risk families appears unequivocal, and modern life still encounters all kinds of unpredictable risks. Contemporary grandparental care is no evolutionary mismatch.
Effects of diurnal variation and prolonged refractoriness on repeated measurements of airways responsiveness to methacholine.
Authors: J R Beach, S C Stenton, M J Connolly, E H Walters, D J Hendrick
Journal: Thorax (1995)

BACKGROUND--A number of studies have suggested that diurnal variation in airways responsiveness underlies the circadian rhythm of ventilatory function in asthma. Measurements of airways responsiveness are therefore often performed at standardised times in order to avoid this possible effect, but this is not practical for epidemiological studies. Refractoriness to methacholine has also been reported and this, too, could confound the results of methacholine tests repeated over short intervals. This investigation was carried out to evaluate the possible magnitude of diurnal variation and refractoriness in repeated measures of airways responsiveness to methacholine. METHODS--To investigate diurnal variation in airways responsiveness, 24 asthmatic subjects aged 18-45 underwent five methacholine tests over three days which were not necessarily consecutive: day 1 at 08:00 hours; day 2 at 08:00 hours, 14:00 hours, 20:00 hours; day 3 at 20:00 hours. To investigate refractoriness a retrospective analysis was undertaken of all paired methacholine tests performed in individuals within our unit between 1984 and 1990 where there had been no intervention likely to affect the results. RESULTS--The first investigation revealed no diurnal change in airways responsiveness although there was a change in FEV1. Mean PD20 did, however, increase 1.57 fold from 08:00 hours on day 1 to 08:00 hours on day 2 for subjects studied on consecutive days. The second investigation confirmed that a test interval of up to 24 hours (but not of 48 or more hours) was associated with a refractory index (PD20 test 2/PD20 test 1) of &gt; 1. CONCLUSIONS--No diurnal variation in airways responsiveness was detected for measurements made between 08:00 hours and 20:00 hours, but an interval between successive tests of up to 24 hours was associated with refractoriness. Diurnal variation is not likely to exert an important confounding effect on methacholine tests carried out between 08:00 hours and 20:00 hours, but confounding could result from refractoriness if tests are repeated at intervals up to 24 hours.