tbuckley/cabot-search huggingface dataset:
Enhanced Fibroblast–Myocyte Interactions in Response to Cardiac Injury
Authors: Carolina Vasquez, Poornima Mohandas, Karen L. Louie, Najate Benamer, Ashwini C. Bapat, Gregory E. Morley
Journal: Circulation Research (2010)

Rationale: A critical event in the development of cardiac fibrosis is the transformation of fibroblasts into myofibroblasts. The electrophysiological consequences of this phenotypic switch remain largely unknown. Objective: Determine whether fibroblast activation following cardiac injury results in a distinct electrophysiological phenotype that enhances fibroblast–myocyte interactions. Methods and Results: Neonatal rat myocyte monolayers were treated with media (CM) conditioned by fibroblasts isolated from normal (Fb) and infarcted (MI-Fb) hearts. Fb and MI-Fb were also plated on top of myocyte monolayers at 3 densities. Cultures were optically mapped after CM treatment or fibroblast plating to obtain conduction velocity and action potential duration (APD 70 ). Intercellular communication and connexin43 expression levels were assessed. Membrane properties of Fb and MI-Fb were evaluated using patch clamp techniques. MI-Fb CM treatment decreased conduction velocity (11.1%) compared to untreated myocyte cultures. APD 70 was reduced by MI-Fb CM treatment compared to homocellular myocyte culture (9.4%) and Fb CM treatment (6.4%). In heterocellular cultures, MI-Fb conduction velocities were different from Fb at all densities (+29.8%, −23.0%, and −16.7% at 200, 400, and 600 cells/mm 2 , respectively). APD 70 was reduced (9.6%) in MI-Fb compared to Fb cultures at 200 cells/mm 2 . MI-Fb had more hyperpolarized resting membrane potentials and increased outward current densities. Connexin43 was elevated (134%) in MI-Fb compared to Fb. Intercellular coupling evaluated with gap fluorescence recovery after photobleaching was higher between myocytes and MI-Fb compared to Fb. Conclusions: These data demonstrate cardiac injury results in significant electrophysiological changes that enhance fibroblast–myocyte interactions and could contribute to the greater incidence of arrhythmias observed in fibrotic hearts.
The survival kinases Akt and Pim as potential pharmacological targets
Authors: R. Amaravadi
Journal: Journal of Clinical Investigation (2005)

The Akt and Pim kinases are cytoplasmic serine/threonine kinases that control programmed cell death by phosphorylating substrates that regulate both apoptosis and cellular metabolism. The PI3K-dependent activation of the Akt kinases and the JAK/STAT–dependent induction of the Pim kinases are examples of partially overlapping survival kinase pathways. Pharmacological manipulation of such kinases could have a major impact on the treatment of a wide variety of human diseases including cancer, inflammatory disorders, and ischemic diseases.
ORGANIZATIONAL DIVERSIFICATION IN THE AMERICAN HOSPITAL
Authors: Timothy S. Snail, James C. Robinson
Journal: Annual Review of Public Health (1998)

▪ Abstract This paper outlines a conceptual framework of organizational diversification and assesses the state of empirical research on hospital organizational change. The literature on economic organization of hospitals, one of the most developed branches of health services research, still has only weak ties to economic theory. Evolving physician-hospital organizations do not fit into existing frameworks based on horizontal integration, vertical integration, or diversification. Empirical research has primarily focused on horizontal integration, and cause-effect relationships are often obscured by models that depart from economic theory and lack controls for self-selection bias. Recent empirical studies indicate that hospital mergers had moderate, rather than dramatic, effects on the rate of change in operating costs, staffing, and scale. Mergers rarely resulted in hospital closure, but were as likely to result in acute care consolidation and restructuring as in conversion to non-acute inpatient uses. While administrative costs were higher in for-profit than non-profit system hospitals, total costs were similar. System hospitals had lower marginal and average costs per stay than independent hospitals. Hospital vertical integration into subacute care was largely an artifact of the governmental uniform pricing system, which encouraged vertical integration. Hospitals that shared governance or financial risks with physicians outperformed those with high levels of physician governance and financial integration (e.g. stock ownership). Formal physician-hospital organizational arrangements often served to coordinate managed care contracting or to forge links with primary care group practices. Hospital diversification into related services improved short-term financial performance over unrelated diversification, although long-term performance was similar.
Subcellular Localization of Activated Leukocyte Cell Adhesion Molecule Is a Molecular Predictor of Survival in Ovarian Carcinoma Patients
Authors: Delia Mezzanzanica, Marina Fabbi, Marina Bagnoli, Samantha Staurengo, Marco Losa, Emanuela Balladore, Paola Alberti, Lara Lusa, Antonino Ditto, Silvano Ferrini, Marco A. Pierotti, Mattia Barbareschi, Silvana Pilotti, Silvana Canevari
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Currently available clinicopathologic prognostic factors are imperfect predictors of clinical course in advanced-stage epithelial ovarian cancer patients. New molecular predictors are needed to identify patients with higher risk of relapse or death from disease. In a retrospective study, we investigated the prognostic impact of activated leukocyte cell adhesion molecule (ALCAM) expression in epithelial ovarian cancer. Experimental Design: We analyzed the effect of cell-anchorage loss on ALCAM cellular localization in vitro and assessed ALCAM expression by immunohistochemistry in a series of 109 well-characterized epithelial ovarian cancer patient samples. Chi-square test, Kaplan-Meier method, and Cox proportional hazard analyses were used to relate ALCAM cellular localization to clinical-pathologic parameters and to overall survival (OS) rate. Results: Loss of epithelial ovarian cancer cell anchorage was associated both in vitro and in vivo with decreased ALCAM membrane expression. In vivo, ALCAM was localized to cell membrane in normal surface ovarian epithelium, whereas in 67% of the epithelial ovarian cancer samples, membrane localization was decreased or even lost, and the molecule was mainly expressed in cytoplasm. Median OS in this group of patients was 58 months, whereas a median OS was not yet reached in patients with ALCAM membrane localization (P = 0.036, hazard ratio [HR] = 2.0, 95% confidence interval [CI] 1.1 to 3.5). In a multivariate Cox regression model including all the available clinicopathologic variables, loss of ALCAM membrane expression was an independent factor of unfavorable prognosis (P = 0.042, HR = 2.15, 95% CI: 1.0 to 4.5). Conclusions: Decreased/lost ALCAM membrane expression is a marker of poorer outcome in epithelial ovarian cancer patients and might help to identify patients who could benefit from more frequent follow-up or alternative therapeutic modalities.
The Calcium Paradoxon of Renin Release
Authors: Christian Grünberger, Birgit Obermayer, Jürgen Klar, Armin Kurtz, Frank Schweda
Journal: Circulation Research (2006)

An increase in the free intracellular calcium concentration promotes exocytosis in most secretory cells. In contrast, renin release from juxtaglomerular (JG) cells is suppressed by calcium. The further downstream signaling cascades of this so called “calcium paradoxon” of renin secretion have been incompletely defined. Because cAMP is the main intracellular stimulator of renin release, we hypothesized that calcium might exert its suppressive effects on renin secretion via the inhibition of the calcium-regulated adenylate cyclases AC5 and AC6. In primary cultures of JG cells, calcium-dependent inhibitors of renin release (angiotensin II, endothelin-1, thapsigargin) suppressed renin secretion, which was paralleled by decreases in intracellular cAMP levels [cAMP]. When [cAMP] was clamped by membrane permeable cAMP derivates, renin release was not suppressed by any of the calcium liberators. Additionally, both endothelin and thapsigargin suppressed cAMP levels and renin release in isoproterenol or forskolin-pretreated As4.1 cells, a renin-producing cell line that expresses AC5 and AC6. The calcium-dependent inhibition of intracellular cAMP levels and renin release was prevented by small interfering RNA-mediated knockdown of AC5 and/or AC6 expression, underlining the functional significance of these AC isoforms in renin-producing cells. Finally, in isolated perfused mouse kidneys, angiotensin II completely inhibited the stimulation of renin secretion induced by adenylate cyclase activation (isoproterenol) but not by membrane permeable cAMP analogs, supporting the conclusion that the suppressive effect of calcium liberators on renin release is mediated by inhibition of adenylate cyclase activity.
Inhibition of nitric oxide generation: Normalization of in vitro insulin secretion in mice with multiple low-dose streptozotocin and in mice injected with mononuclear splenocytes from diabetic syngeneic donors
Authors: L.M. Karabatas, L. Fabiano de Bruno, C.F. Pastorale, C. Cullen, J.C. Basabe
Journal: Metabolism (1996)
Decreased nailfold capillary density in Raynaud's phenomenon: a reflection of immunologically mediated local and systemic vascular disease?
Authors: P M Houtman, C G Kallenberg, A A Wouda, T H The
Journal: Annals of the Rheumatic Diseases (1985)

Nailfold capillary patterns were studied in 107 patients with Raynaud's phenomenon (RP), including patients wih (n = 39) and without (n = 68) connective tissue disease (CTD). Capillary density was decreased in patients with sclerodactyly, digital ulcers, tuft resorption, and telangiectasia, compared with patients without these symptoms. In addition, an inverse relationship was found between the severity of RP at first presentation (as graded by photoelectric plethysmography during cooling) and the capillary density in patients with CTD (r = -0.45; p less than 0.05). In the total group of patients nailfold capillary density was inversely related to organ system involvement (r = -0.52; p less than 0.01). Decreased nailfold capillary density was observed, in particular, in patients with oesophageal hypomotility and in patients with chest x-rays compatible with interstitial fibrosis. As to factors supposedly involved in the pathogenesis of vascular changes in CTD, the presence of autoantibodies, increased levels of circulating immune complexes, and increased levels of acute phase reactants were all associated with a decreased number of nailfold capillaries. We conclude that loss of nailfold capillaries as observed by microscopy is a reflection of local and systemic vascular disease.
The Efficacy and Cost of Alternative Strategies for Systematic Screening for Type 2 Diabetes in the U.S. Population 45–74 Years of Age
Authors: Susan L. Johnson, Bahman P. Tabaei, William H. Herman
Journal: Diabetes Care (2005)

To simulate the outcomes of alternative strategies for screening the U.S. population 45-74 years of age for type 2 diabetes.We simulated screening with random plasma glucose (RPG) and cut points of 100, 130, and 160 mg/dl and a multivariate equation including RPG and other variables. Over 15 years, we simulated screening at intervals of 1, 3, and 5 years. All positive screening tests were followed by a diagnostic fasting plasma glucose or an oral glucose tolerance test. Outcomes include the numbers of false-negative, true-positive, and false-positive screening tests and the direct and indirect costs.At year 15, screening every 3 years with an RPG cut point of 100 mg/dl left 0.2 million false negatives, an RPG of 130 mg/dl or the equation left 1.3 million false negatives, and an RPG of 160 mg/dl left 2.8 million false negatives. Over 15 years, the absolute difference between the most sensitive and most specific screening strategy was 4.5 million true positives and 476 million false-positives. Strategies using RPG cut points of 130 mg/dl or the multivariate equation every 3 years identified 17.3 million true positives; however, the equation identified fewer false-positives. The total cost of the most sensitive screening strategy was $42.7 billion and that of the most specific strategy was $6.9 billion.Screening for type 2 diabetes every 3 years with an RPG cut point of 130 mg/dl or the multivariate equation provides good yield and minimizes false-positive screening tests and costs.
FOXO3a-dependent regulation of Puma in response to cytokine/growth factor withdrawal
Authors: Han You, Marc Pellegrini, Katsuya Tsuchihara, Kazuo Yamamoto, Georg Hacker, Miriam Erlacher, Andreas Villunger, Tak W. Mak
Journal: The Journal of Experimental Medicine (2006)

Puma is an essential mediator of p53-dependent and -independent apoptosis in vivo. In response to genotoxic stress, Puma is induced in a p53-dependent manner. However, the transcription factor driving Puma up-regulation in response to p53-independent apoptotic stimuli has yet to be identified. Here, we show that FOXO3a up-regulates Puma expression in response to cytokine or growth factor deprivation. Importantly, dysregulated Akt signaling in lymphoid cells attenuated Puma induction upon cytokine withdrawal. Our results suggest that Puma, together with another BH3 only member, Bim, function as FOXO3a downstream targets to mediate a stress response when PI3K/Akt signaling is down-regulated.
Women’s Experiences With Isotretinoin Risk Reduction Counseling
Authors: Carly A. Werner, Melissa J. Papic, Laura K. Ferris, Jessica K. Lee, Sonya Borrero, Noel Prevost, Eleanor Bimla Schwarz
Journal: JAMA Dermatology (2013)

Isotretinoin, an effective anti-acne therapy, is a known teratogen that is strictly regulated through the iPLEDGE program. However, since this program has not significantly reduced rates of pregnancies exposed to isotretinoin, new strategies for reducing rates of isotretinoin-exposed pregnancies are needed.To explore women's experiences with counseling about isotretinoin risk reduction.Structured interviews were conducted between January and September 2012. Two independent coders performed content analysis using a grounded theory approach. The study participants were 16 women who had used isotretinoin to treat severe skin disease and who were recruited from a single urban community via flyers displayed on college campuses, at dermatology clinics, and at student health facilities.Perceptions of isotretinoin-associated risks and understanding of ways teratogenic risks can be avoided.Participants clearly understood that isotretinoin is teratogenic but had less understanding of contraceptive methods that effectively prevent pregnancy. Most described the counseling they received as anxiety provoking. Few were counseled about highly effective reversible contraceptives such as the subdermal implant or intrauterine contraception; most counseling focused on oral contraceptives. Women cited multiple influences on their contraceptive choices, including friends, family, physicians, the internet, and other media; however, some expressed concerns about the accuracy of these sources of information. For many, iPLEDGE was their first introduction to contraception. When presented with evidence-based information on the relative effectiveness of available contraceptives, participants expressed surprise that this was not part of the iPLEDGE materials.Since few clinicians provide women information on highly effective (ie, intrauterine or subdermal) contraceptives, the iPLEDGE program increases anxiety about isotretinoin more than it helps women feel protected from the teratogenic risks of isotretinoin.
In Vitro Suppression of Immunocompetent Cells by Lymphomas From Aging Mice 2
Authors: B. N. Jaroslow, K. M. Suhrbier, R. J. M. Fry, S. A. Tyler
Journal: JNCI Journal of the National Cancer Institute (1975)

We studied the effects of lymphomas in the spleens of aging (C57BL/6 × BALB/c)F1 (B6CF1) mice on the immunologic responsiveness of normal spleen cell cultures to sheep erythrocytes. The cultures were assayed for antibody-forming cells (AFC). Cultures of 20×106 normal spleen cells produced hundreds of AFC, whereas similar cultures of lymphomatous spleen cells produced less than ten AFC. Normal spleen cells were immunosuppressed in cultures with as few as 104 lymphomatous spleen cells. Our results demonstrated that lymphoma cells inhibited the response of normal spleen cells to antigenic stimulation in vitro. The age response for male mice gave a biphasic decline with a steeper second phase. This second decline of immune responsiveness started to appear as the incidence of lymphomas rose. This suggested that the immunosuppressive activity of lymphoma cells was causally related to the age-dependent decline of immune responsiveness in B6CF1 mice.
Superhydrophobic modification fails to improve the performance of small diameter expanded polytetrafluoroethylene vascular grafts
Authors: G.J Toes, K.W van Muiswinkel, W van Oeveren, A.J.H Suurmeijer, W Timens, I Stokroos, J.J.A.M van den Dungen
Journal: Biomaterials (2002)
Medicaid Managed Care: Contribution to Issues of Health Reform
Authors: Deborah A. Freund, Robert E. Hurley
Journal: Annual Review of Public Health (1995)

This chapter examines the emergence of managed care in Medicaid from an alternative to the mainstream delivery system for many beneficiaries. It offers a definition that encompasses the broad spectrum of program manifestations, and presents a brief historical perspective on the major eras of managed care in Medicaid, The major program prototypes are described and their contribution to enrollment growth is discussed. Research evidence is examined to address both operational issues and program impacts. Finally, we conclude with an appraisal of contemporary issues of importance and speculation on the next generation of Medicaid managed care programs with an eye to how federal and state health care reform proposals will shape this future.
RESPONSE: Testing for Colon Neoplasia Susceptibility Variants at the Human COX2 Locus
Authors: G. L. Wiesner, P. Platzer, S. G. Buxbaum, S. Lewis, M. Macmillen, J. Willis, A. Chakravarti, R. C. Elston, S. D. Markowitz
Journal: JNCI Journal of the National Cancer Institute (2001)
Type-specific radioimmunoassays for the gp70s of mink cell focus-inducing murine leukemia viruses: expression of a cross-reacting antigen in cells infected with the friend strain of the spleen focus-forming virus
Authors: S Ruscetti, D Linemeyer, J Feild, D Troxler, E Scolnick
Journal: The Journal of Experimental Medicine (1978)

We have isolated the gp70 of a helper-independent strain of a Friend mink cell focus-inducing (MCF) virus, Fr-MCF-1. This recombinant virus, like the previously described AKR-MCF viruses, has been shown by both biological and biochemical means to be an envelope gene recombinant between Friend murine leukemia virus (F-MuLV) and a mouse xenotropic virus. Utilizing (125)I- labeled Fr-MCF-1 gp70 and antiserum prepared against an MCF strain of Moloney type-C virus (Mol-MCF(83)), we have developed a radioimmunoassay which detects immunological determinant (s)contained in the gp70s of MCF viruses derived from F-MuLV, Mol-MuLV, and AKR-MuLV. This MCF determinant(s) is not detected in the ecotropic parents of each of these MCF viruses, nor in helper-independent murine xenotropic viruses derived from Swiss or BALB/c mice. A protein partially cross-reactive with the MCF gp70 determinant(s) is detected in a replicating xenotropic virus derived from NZB mice. Utilizing this MCF gp70 specific immunoassay, we can detect a cross-reacting gene product coded for by the Friend strain of the spleen focus-forming virus (SFFV) in rat fibroblasts nonproductively infected with SFFV. The results support earlier molecular hybridization studies which indicated that the genome of SFFV contains genetic information derived from both F-MuLV and xenotropic virus, and that the xenotropic-related sequences in SFFV are highly related to those found in MCF murine type-C viruses.
Impairment of endothelium dependent responses in a rat model of chronic heart failure: effects of an exercise training protocol
Authors: D C Lindsay, C Jiang, F Brunotte, S Adamopoulos, A J Coats, B Rajagopalan, P A Poole-Wilson, P Collins
Journal: Cardiovascular Research (1992)

Journal Article Impairment of endothelium dependent responses in a rat model of chronic heart failure: effects of an exercise training protocol Get access D C Lindsay, D C Lindsay Correspondence to Dr Lindsay. Search for other works by this author on: Oxford Academic PubMed Google Scholar C Jiang, C Jiang Search for other works by this author on: Oxford Academic PubMed Google Scholar F Brunotte, F Brunotte Search for other works by this author on: Oxford Academic PubMed Google Scholar S Adamopoulos, S Adamopoulos Search for other works by this author on: Oxford Academic PubMed Google Scholar A J S Coats, A J S Coats Search for other works by this author on: Oxford Academic PubMed Google Scholar B Rajagopalan, B Rajagopalan Search for other works by this author on: Oxford Academic PubMed Google Scholar P A Poole-Wilson, P A Poole-Wilson Search for other works by this author on: Oxford Academic PubMed Google Scholar P Collins P Collins Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 7, July 1992, Pages 694–697, https://doi.org/10.1093/cvr/26.7.694 Published: 01 July 1992 Article history Received: 30 April 1991 Accepted: 07 January 1992 Published: 01 July 1992