tbuckley/cabot-search huggingface dataset:
α-Adrenergic Control of Volume-Regulated Cl <sup>−</sup> Currents in Rabbit Atrial Myocytes
Authors: Dayue Duan, Bernard Fermini, Stanley Nattel
Journal: Circulation Research (1995)

alpha-Adrenergic stimulation is known to play a role in cardiac arrhythmogenesis and to modulate a variety of cardiac K+ currents. The effects of alpha-adrenergic stimulation on Cl- currents are largely unknown. Many cardiac cell types show a volume-sensitive Cl- current induced by cell swelling (ICl.swell). The present experiments were designed to assess the potential alpha-adrenergic modulation of ICl.swell in rabbit atrial myocytes. ICl.swell was induced with the use of a hypotonic superfusate, under conditions designed to prevent currents carried by K+, Na+, and Ca2+ ions. A basal Cl- current (ICl.b) was observed under isotonic conditions in 128 of 150 cells (85%), had the same dependency on [Cl-]o as ICl.swell, and was reduced by cell shrinkage induced by hypertonic superfusion, suggesting that ICl.b is carried by the same volume-sensitive Cl- conductance as ICl.swell. Phenylephrine produced a concentration-dependent and near-complete inhibition of ICl.b and ICl.swell, with EC50 values of 86 +/- 5 and 72 +/- 7 (mean +/- SEM) mumol/L, respectively, at +20 mV. Norepinephrine (administered in the presence of 1 mumol/L propranolol) also inhibited ICl.b and ICl.swell, with EC50 values of 2.6 +/- 0.1 and 2.8 +/- 0.4 mumol/L, respectively. The concentration-response curve for phenylephrine was shifted significantly (P < .001) to the right by the alpha 1-adrenoceptor antagonist prazosin and by the alpha 1A-receptor antagonists (+)-niguldipine and 5-methylurapidil but was unaltered by the alpha 1B-receptor antagonist chloroethylclonidine (100 mumol/L). Inhibition of protein kinase C (PKC) with staurosporine, H-7, or 18-hour preincubation with the phorbol ester 4 beta-phorbol 12-myristate 13-acetate (PMA, 500 nmol/L) blocked the effects of phenylephrine on ICl.swell, and the highly selective PKC inhibitor bisindolylmaleimide blocked the effects of norepinephrine on ICl.swell and ICl.b. Both PMA and 1-oleoyl-2-acetylglycerol inhibited ICl.swell in a concentration-dependent fashion. In blinded studies, the phorbol ester phorbol 12,13-didecanoate (PDD) reduced ICl.swell by 91 +/- 3%; its inactive analogue 4 alpha-PDD had no effect (mean change, 3 +/- 1%). Preincubation with pertussis toxin (PTX) prevented the actions of phenylephrine on ICl.swell, indicating a role for a PTX-sensitive guanine nucleotide-binding (G) protein. We conclude that alpha-adrenergic agonists inhibit volume-sensitive Cl- currents in rabbit atrial cells by interacting with an alpha 1A-adrenoceptor mechanism that is coupled to PKC via a PTX-sensitive G protein.(ABSTRACT TRUNCATED AT 400 WORDS)
Survival in Academy Award–Winning Actors and Actresses
Authors: Donald A. Redelmeier, Sheldon M. Singh
Journal: Annals of Internal Medicine (2001)

Background: Social status is an important predictor of poor health. Most studies of this issue have focused on the lower echelons of society. Objective: To determine whether the increase in status from winning an academy award is associated with long-term mortality among actors and actresses. Design: Retrospective cohort analysis. Setting: Academy of Motion Picture Arts and Sciences. Participants: All actors and actresses ever nominated for an academy award in a leading or a supporting role were identified (n = 762). For each, another cast member of the same sex who was in the same film and was born in the same era was identified (n = 887). Measurements: Life expectancy and all-cause mortality rates. Results: All 1649 performers were analyzed; the median duration of follow-up time from birth was 66 years, and 772 deaths occurred (primarily from ischemic heart disease and malignant disease). Life expectancy was 3.9 years longer for Academy Award winners than for other, less recognized performers (79.7 vs. 75.8 years; P = 0.003). This difference was equal to a 28% relative reduction in death rates (95% CI, 10% to 42%). Adjustment for birth year, sex, and ethnicity yielded similar results, as did adjustments for birth country, possible name change, age at release of first film, and total films in career. Additional wins were associated with a 22% relative reduction in death rates (CI, 5% to 35%), whereas additional films and additional nominations were not associated with a significant reduction in death rates. Conclusion: The association of high status with increased longevity that prevails in the public also extends to celebrities, contributes to a large survival advantage, and is partially explained by factors related to success.
Randomized double‐blind controlled study with sublingual carbamylated allergoid immunotherapy in mild rhinitis due to mites
Authors: G. Passalacqua, M. Pasquali, R. Ariano, C. Lombardi, A. Giardini, I. Baiardini, G. Majani, P. Falagiani, M. Bruno, G. W. Canonica
Journal: Allergy (2006)

The clinical efficacy of sublingual immunotherapy (SLIT) in mite allergy and in mild disease is still a matter of debate, thus we performed a long-term clinical trial.The study was randomized, double-blind and placebo-controlled. After a 1-year assessment, 68 patients with mild rhinitis with/without asthma due to mites were randomized to drugs + placebo or drugs + SLIT for 2 years. Sublingual immunotherapy was given as soluble tablets of monomeric carbamylated allergoid. Clinical scores for asthma and rhinitis (0, absent to 3, severe) and drug consumption were assessed by diary card in the period November-February. Quality of life was assessed before and after each observation period and pharmaco-economy data were evaluated as well.Fifty-six patients completed the study. The rate of dropouts was similar in the two groups. No relevant side effect was reported. There was a significant reduction of total clinical scores (P < 0.05) in the active group vs placebo at the first year, but not at the second whereas nasal obstruction significantly improved in both years (P < 0.05). The reduction of drug intake score was significant only at the first year. No change was observed concerning most of the Short Form-36 items, because at baseline all patients displayed a normal profile. A significant change in SLIT group was seen for the item 'change in health status'. The need for extra visits was significantly lower in the active group (25%vs 43%).Sublingual immunotherapy was clinically effective and safe in mite-induced mild disease.
Oncogenic Herpesvirus HHV-8 Promotes Androgen-Independent Prostate Cancer Growth
Authors: Justin G. Mygatt, Adit Singhal, Gauthaman Sukumar, Clifton L. Dalgard, Johnan A.R. Kaleeba
Journal: Cancer Research (2013)

Mechanisms underlying progression to androgen-independent prostate cancer following radical ablation therapy remain poorly defined. Although intraprostatic infections have been highlighted as potential cofactors, pathogen influences on pathways that support tumor regrowth are not known. To explore this provocative concept, we derived androgen-sensitive and -insensitive prostate epithelial cells persistently infected with human herpesvirus 8 (HHV-8), an oncogenic herpesvirus that has been detected in normal prostate epithelium, prostate adenocarcinoma, and biologic fluids of patients with prostate cancer, to explore its effects on transition to hormone-refractory disease. Strikingly, we found that HHV-8 infection of androgen-sensitive prostate cancer cells conferred the capacity for androgen-independent growth. This effect was associated with altered expression and transcriptional activity of the androgen receptor (AR). However, HHV-8 infection bypassed AR signaling by promoting enhancer of zeste homolog 2 (EZH2)-mediated epigenetic silencing of tumor-suppressor genes, including MSMB and DAB2IP that are often inactivated in advanced disease. Furthermore, we found that HHV-8 triggered epithelial-to-mesenchymal transition. Although HHV-8 has not been linked etiologically to prostate cancer, virologic outcomes revealed by our study provide mechanistic insight into how intraprostatic infections could constitute risk for progression to androgen-independent metastatic disease where EZH2 has been implicated. Taken together, our findings prompt further evaluations of the relationship between HHV-8 infections and risk of advanced prostate cancer.
Fat May Fuel Breast Cancer Growth
Authors: K. Hede
Journal: JNCI Journal of the National Cancer Institute (2008)

cancer. New evidence from several fronts suggests that excess body fat promotes breast cancer growth and that reducing body fat and increasing physical activity im prove the odds of survival. Results of the Million Woman Study, a longitudinal cohort study of 1.2 million women in the U.K., concluded that being overweight or obese is associated with a higher risk of postmenopausal breast cancer and lower survival. The report, published in
Pulsatile Versus Oscillatory Shear Stress Regulates NADPH Oxidase Subunit Expression
Authors: Juliana Hwang, Michael H. Ing, Adler Salazar, Bernard Lassègue, Kathy Griendling, Mohamad Navab, Alex Sevanian, Tzung K. Hsiai
Journal: Circulation Research (2003)

Shear stress regulates endothelial nitric oxide and superoxide (O 2 −· ) production, implicating the role of NADPH oxidase activity. It is unknown whether shear stress regulates the sources of reactive species production, consequent low-density lipoprotein (LDL) modification, and initiation of inflammatory events. Bovine aortic endothelial cells (BAECs) in the presence of 50 μg/mL of native LDL were exposed to (1) pulsatile flow with a mean shear stress (τ ave ) of 25 dyne/cm 2 and (2) oscillating flow at τ ave of 0. After 4 hours, aliquots of culture medium were collected for high-performance liquid chromatography analyses of electronegative LDL species, described as LDL − and LDL 2− . In response to oscillatory shear stress, gp91 phox mRNA expression was upregulated by 2.9±0.3-fold, and its homologue, Nox4, by 3.9±0.9-fold ( P &lt;0.05, n=4), with a corresponding increase in O 2 −· production rate. The proportion of LDL − and LDL 2− relative to static conditions increased by 67±17% and 30±7%, respectively, with the concomitant upregulation of monocyte chemoattractant protein-1 expression and increase in monocyte/BAEC binding ( P &lt;0.05, n=5). In contrast, pulsatile flow downregulated both gp91 phox and Nox4 mRNA expression (by 1.8±0.2-fold and 3.0±0.12-fold, respectively), with an accompanying reduction in O 2 −· production, reduction in the extent of LDL modification (51±12% for LDL − and 30±7% for LDL 2− ), and monocyte/BAEC binding. The flow-dependent LDL oxidation is determined in part by the NADPH oxidase activity. The formation of modified LDL via O 2 −· production may also affect the regulation of monocyte chemoattractant protein-1 expression and monocyte/BAEC binding.
NHANES III
Authors: Robert N. Foley, Changchun Wang, Areef Ishani, Allan J. Collins
Journal: Journal of the American Society of Nephrology (2007)

Whether the creatinine-based glomerular filtration rate (GFR) thresholds used to define chronic kidney disease (CKD) identify metabolic abnormalities similarly in minority and nonminority populations is unknown. We addressed this question among adult participants in the Third National Health and Nutrition Examination Survey (NHANES III) (n = 15,837). GFR was estimated from serum creatinine values and metabolic abnormalities were defined by 5th or 95th percentile values. After adjustment for age, demographic characteristics, and GFR, black participants were significantly more likely than white participants to have abnormal levels of systolic and diastolic blood pressure, hemoglobin, phosphorus, and uric acid. Hispanic subjects were significantly more likely to have abnormal levels of systolic blood pressure, hemoglobin, bicarbonate, and phosphorus. Among participants with GFR < 60 mL/min per 1.73 m(2), black participants were significantly more likely to have abnormal levels of systolic and diastolic blood pressure, hemoglobin, and uric acid; Hispanic subjects were significantly more likely to have abnormal systolic blood pressure levels. Metabolic abnormalities were more common in minority populations, and low GFR appeared to have a multiplicative effect. Defining CKD using a single GFR threshold may be disadvantageous for minority populations because metabolic abnormalities are present at higher levels of GFR.
Miliary disease of the lung: What is your diagnosis?
Authors: Hanen Njeh, Hanen Abid, Moez Bradaii, Sameh Msaaed, Khaireddine Ben Mahfoudh
Journal: European Respiratory Journal (2013)

Introduction:

Miliary shadows in the lung are not uncommon and are seen in a wide variety of diseases. Miliary pattern consists with the presence of multiple small (usually 1 to 3 mm in diameter) nodules in the lung with sharp margins.

Aims:

A heterogeneous group of conditions comprising more than 80 entities may display miliary pattern. We expose the most common entities. The radiologic features that help in the differential diagnosis are discussed.

Methods:

We report the cases of 20 patients (12 women and 8 men) with military lung disease. They were aged between 14 and 76 years. All of them were explored by a chest radiography and a high-resolution computed tomography.

Results:

According to the distribution of the nodules in relation to the secondary lobule, high-resolution computed tomography findings divide miliary patterns into 3 groups: centrilobular, perilymphatic, and random presentation. The entities found with this pattern are miliary tuberculosis (12 cases),sarcoidosis (2 cases), adenocarcinoma (3 cases), metastases (1 case), and silicosis (2 cases).

Conclusion

High-resolution computed tomography can help to narrow the differential diagnosis of miliary lung diseases. In selected cases the distribution of the nodules, associated radiologic findings and clinical features point to a definite etiologic diagnosis.
Numerical and comparative three‐dimensional structural analysis of peripheral nerve fibres in epidermis of patients with atopic dermatitis
Authors: M. Tsutsumi, H. Kitahata, M. Fukuda, J. Kumamoto, M. Goto, S. Denda, K. Yamasaki, S. Aiba, M. Nagayama, M. Denda
Journal: British Journal of Dermatology (2015)

Journal Article Numerical and comparative three‐dimensional structural analysis of peripheral nerve fibres in epidermis of patients with atopic dermatitis Get access M. Tsutsumi, M. Tsutsumi Japan Science and Technology Agency, CREST Kawaguchi JapanShiseido Research Center 2‐2‐1 Hayabuchi Tsuzuki‐ku Yokohama 224‐8558 Japan Search for other works by this author on: Oxford Academic Google Scholar H. Kitahata, H. Kitahata Japan Science and Technology Agency, CREST Kawaguchi JapanDepartment of Physics Graduate School of Science Chiba University Chiba Japan Search for other works by this author on: Oxford Academic Google Scholar M. Fukuda, M. Fukuda Shiseido Research Center 2‐2‐1 Hayabuchi Tsuzuki‐ku Yokohama 224‐8558 Japan Search for other works by this author on: Oxford Academic Google Scholar J. Kumamoto, J. Kumamoto Japan Science and Technology Agency, CREST Kawaguchi JapanResearch Institute for Electronic Science Hokkaido University Sapporo Japan Search for other works by this author on: Oxford Academic Google Scholar M. Goto, M. Goto Japan Science and Technology Agency, CREST Kawaguchi JapanShiseido Research Center 2‐2‐1 Hayabuchi Tsuzuki‐ku Yokohama 224‐8558 Japan Search for other works by this author on: Oxford Academic Google Scholar S. Denda, S. Denda Japan Science and Technology Agency, CREST Kawaguchi JapanShiseido Research Center 2‐2‐1 Hayabuchi Tsuzuki‐ku Yokohama 224‐8558 Japan Correspondence: Mitsuhiro Denda. E‐mail: mitsuhiro.denda@to.shiseido.co.jp Search for other works by this author on: Oxford Academic Google Scholar K. Yamasaki, K. Yamasaki Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan Search for other works by this author on: Oxford Academic Google Scholar S. Aiba, S. Aiba Department of Dermatology Tohoku University Graduate School of Medicine Sendai Japan Search for other works by this author on: Oxford Academic Google Scholar M. Nagayama, M. Nagayama Japan Science and Technology Agency, CREST Kawaguchi JapanResearch Institute for Electronic Science Hokkaido University Sapporo Japan Search for other works by this author on: Oxford Academic Google Scholar M. Denda M. Denda Japan Science and Technology Agency, CREST Kawaguchi JapanShiseido Research Center 2‐2‐1 Hayabuchi Tsuzuki‐ku Yokohama 224‐8558 Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 1, 1 January 2016, Pages 191–194, https://doi.org/10.1111/bjd.13974 Published: 01 January 2016
Cytoplasmic p21 expression levels determine cisplatin resistance in human testicular cancer
Authors: Roelof Koster, Alessandra di Pietro, Hetty Timmer-Bosscha, Johan H. Gibcus, Anke van den Berg, Albert J. Suurmeijer, Rainer Bischoff, Jourik A. Gietema, Steven de Jong
Journal: Journal of Clinical Investigation (2010)

Platinum-based chemotherapies such as cisplatin are used as first-line treatment for many cancers. Although there is often a high initial responsiveness, the majority of patients eventually relapse with platinum-resistant disease. For example, a subset of testicular cancer patients still die even though testicular cancer is considered a paradigm of cisplatin-sensitive solid tumors, but the mechanisms of chemoresistance remain elusive. Here, we have shown that one key determinant of cisplatin-resistance in testicular embryonal carcinoma (EC) is high cytoplasmic expression of the cyclin-dependent kinase (CDK) inhibitor p21. The EC component of the majority of refractory testicular cancer patients exhibited high cytoplasmic p21 expression, which protected EC cell lines against cisplatin-induced apoptosis via CDK2 inhibition. Localization of p21 in the cytoplasm was critical for cisplatin resistance, since relocalization of p21 to the nucleus by Akt inhibition sensitized EC cell lines to cisplatin. We also demonstrated in EC cell lines and human tumor tissue that high cytoplasmic p21 expression and cisplatin resistance of EC were inversely associated with the expression of Oct4 and miR-106b seed family members. Thus, targeting cytoplasmic p21, including by modulation of the Oct4/miR-106b/p21 pathway, may offer new strategies for the treatment of chemoresistant testicular and other types of cancer.
FRA-1 Proto-Oncogene Induces Lung Epithelial Cell Invasion and Anchorage-Independent Growth <i>In vitro</i>, but Is Insufficient to Promote Tumor Growth <i>In vivo</i>
Authors: Pavan Adiseshaiah, Daniel J. Lindner, Dhananjaya V. Kalvakolanu, Sekhar P. Reddy
Journal: Cancer Research (2007)

Abstract FRA-1 forms activator protein-1 complexes in association with members of the JUN family and drives gene transcription. FRA-1 has been implicated in the development of airway squamous metaplasia and is frequently overexpressed in squamous cell carcinomas of the esophagus and stomach. We and others have shown a high level of persistent induction of FRA-1 by lung carcinogens, such as cigarette smoke and asbestos, in pulmonary epithelial cells. However, the exact roles of FRA-1 in regulating lung epithelial cell growth and invasion are poorly understood. To examine this aspect, we have stably overexpressed FRA-1 in human type-II–like alveolar malignant cell line (A549) and a nonmalignant bronchial epithelial cell line (BEAS-2B). FRA-1 greatly enhanced the rate of proliferation, motility, and invasion of A549 and BEAS-2B cells. In athymic nude mice, FRA-1, but not the control vector, rapidly enhanced tumor formation and metastasis by A549 cells. In contrast, FRA-1 failed to promote tumor formation by BEAS-2B. We suggest that FRA-1 can promote motility, invasion, and anchorage-independent growth of lung epithelial cells in vitro, but is insufficient for tumor formation. [Cancer Res 2007;67(13):6204–11]
Pulmonary hypertension caused by congestive heart failure is ameliorated by long-term application of an endothelin receptor antagonist Increased expression of endothelin-1 messenger ribonucleic acid and endothelin-1-like immunoreactivity in the lung in congestive heart failure in rats
Authors: Satoshi Sakai, Takashi Miyauchi, Takeshi Sakurai, Iwao Yamaguchi, Masahiko Kobayashi, Katsutoshi Goto, Yasuro Sugishita
Journal: Journal of the American College of Cardiology (1996)
Collagen breakdown products and lung collagen metabolism: an in vitro study on fibroblast cultures.
Authors: C Gardi, P Calzoni, P Marcolongo, E Cavarra, L Vanni, G Lungarella
Journal: Thorax (1994)

BACKGROUND--In fibrotic diseases such as pulmonary fibrosis there is evidence suggesting enhanced synthesis and degradation of lung connective tissue components, including collagen. It has therefore been hypothesised that products of collagen degradation may have a role in the promotion of collagen deposition. In support of this hypothesis, it has recently been shown that intravenous injection of lung collagen degradation products in experimental animals stimulated collagen synthesis leading to increased collagen deposition and diffuse interstitial lung disease. METHODS--Rabbit and human fibroblast cultures from lung and skin were used as an in vitro model to study the responses of these cells to rabbit collagen degradation products. The effects of an acute exposure to collagen degradation products on synthesis of collagen and noncollagenous protein have been studied in confluent cultures by [3H]-proline incorporation. The effects of collagen degradation products on fibroblast proliferation and production of genetic types of collagen have also been investigated. RESULTS--The acute exposure of rabbit lung fibroblast cultures to collagen degradation products significantly increased collagen synthesis without affecting non-collagenous protein synthesis. This effect was dose related, specific for lung fibroblasts, and species specific. Collagen degradation products altered the rate of synthesis of genetic types of collagen with a consequent decrease of type III/I+III collagen ratio (0.26 (0.04) treated with collagen degradation products; 0.45 (0.02) controls). These effects occurred without the intervention of serum factors. In addition, collagen degradation products neither affected fibroblast proliferation nor selected specific clones emphasising one type of collagen. CONCLUSIONS--These results suggest that collagen degradation products can influence lung collagen metabolism by stimulating collagen synthesis. The regulation of collagen mass by collagen degradation products may be of importance in lung collagen homeostasis in vivo.
Investigating the role of CD24 gene polymorphisms in rheumatoid arthritis
Authors: E Sanchez, B Fernandez-Gutierrez, M A Gonzalez-Gay, A Balsa, A Garcia, L Rodriguez, D Pascual-Salcedo, M F Gonzalez-Escribano, J Martin
Journal: Annals of the Rheumatic Diseases (2008)

Rheumatoid arthritis (RA) is a systemic autoimmune disease with a complex pathogenesis which involves genetic and environmental factors.1 CD24 is a glycosylphosphatidylinositol-anchored cell surface protein with expression in a wide variety of cell types which participate in the pathogenesis of RA. This molecule has been proposed as a genetic checkpoint in T-cell homoeostasis and pathogenesis of autoimmune diseases.2 A non-synonymous variation (A57V) and a dinucleotide deletion in the 3′ untranslated region (TG/del) have been associated with different autoimmune diseases, such as multiple sclerosis and systemic lupus erythematosus.3–6 Furthermore, both polymorphisms appear to play a functional role in CD24 expression and CD24 mRNA stability. This gene is located …