tbuckley/cabot-search huggingface dataset:
Electrophysiological responses of cardiac muscle to isoproterenol covalently linked to glass beads.
Authors: E Becker, W R Ingebretsen, S E Mayer
Journal: Circulation Research (1977)

We investigated the effects of isoproterenol aryl glass beads on the electrical properties of cardiac muscle and related these to our previous results concerning biochemical and contractile effects (Ingebretsen et al., Circ, Rs., 40: 474-484, 1977). Beads (10-15) were placed near one end to guinea pig papillary muscles mounted horizontally in a bath perfused with Krebs-Henseleit solution at 30 degrees C and stimulated at 0.2 Hz. The beads produced increased tension and elevation and slight lengthening of the plateau potential when [k+]o = 3.8 mM. After depolarization to a resting potential of -49 mV with [K+]o = 22 mM, isoproterenol beads restored contraction to a comparable extent as occurred with 10(-8) M soluble drug. During field stimulation, action potentials were initiated at the site of bead application and spread decrementally. When beads were placed distal to the site of point stimulation, virtually no excitation could be obtained from cells in the vicinity of the beads. When they were placed close to the stimulating electrode, the beads increased excitability and typical slow action potentials spread to the other end of the muscle. These potentials had the characteristics associated with the slow inward Ca2+ current. The slow channel blocker, D-600, blocked responses to isoproterenol beads. Tetrodotoxin caused responses similar to those obtained with K+ depolarization. The beads probably act by stimulating only a small fraction of the papillary muscle catecholamine receptors. Spread of action potentials from these sites and propagated tension depend on Ca2+ influx, but the nature of an intermediate messenger involved in the propagation of contractions is unknown.
Suppression of caveolin expression induces androgen sensitivity in metastatic androgen-insensitive mouse prostate cancer cells
Authors: Yasutomo Nasu, Terry L. Timme, Guang Yang, Chris H. Bangma, Likun Li, Chengzhen Ren, Sang Hee Park, Marlene DeLeon, Jianxiang Wang, Timothy C. Thompson
Journal: Nature Medicine (1998)
Lack of Correlation between Expression of HIF-1α Protein and Oxygenation Status in Identical Tissue Areas of Squamous Cell Carcinomas of the Uterine Cervix
Authors: Arnulf Mayer, Alexander Wree, Michael Höckel, Cornelia Leo, Henryk Pilch, Peter Vaupel
Journal: Cancer Research (2004)

Hypoxia inducible factor-1alpha (HIF-1alpha) has been proposed as a candidate endogenous marker of tumor hypoxia and as a molecular mediator of hypoxia-driven malignant progression and acquired treatment resistance. In this study, HIF-1alpha expression in 68 biopsies of oxygenation measurement tracks from squamous cell carcinomas of the uterine cervix of 38 patients was assessed. Expression of HIF-1alpha was commonly found to increase as a function of distance from microvessels, at the center of tumor cell aggregations, and in the vicinity of necrotic areas. However, there was no correlation of HIF-1alpha expression with median oxygen tension (oxygen partial pressure; pO2) and hypoxic fractions (hypoxic fraction < 2.5 mm Hg, hypoxic fraction < 5 mm Hg). The results indicate that HIF-1alpha should not be used as an endogenous marker of tumor hypoxia in locally advanced squamous cell carcinomas of the uterine cervix. Additionally, no significant prognostic impact of HIF-1alpha expression was found in this group of patients.
Insurance Coverage and Care of Patients with Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: James E. Calvin, Matthew T. Roe, Anita Y. Chen, Rajendra H. Mehta, Gerard X. Brogan, Elizabeth R. DeLong, Dan J. Fintel, W. Brian Gibler, E. Magnus Ohman, Sidney C. Smith, Eric D. Peterson
Journal: Annals of Internal Medicine (2006)

The impact of insurance coverage on the care of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) is unclear.To compare NSTE ACS care patterns by insurance type.Comparison of Medicaid patients younger than 65 years of age and Medicare patients 65 years of age or older with patients of similar age who have health maintenance organization (HMO) or private insurance coverage.521 U.S. hospitals participating in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC [American College of Cardiology]/AHA [American Heart Association] Guidelines) quality improvement initiative from January 2001 through March 2005.37,345 NSTE ACS patients younger than 65 years of age and 59,550 patients 65 years of age or older.Guideline-recommended treatments, and in-hospital outcomes.Medicaid was the primary payer for 18.7% (6999 of 37,345) of patients younger than age 65 years, whereas Medicare was the primary payer for 67.5% (40,199 of 59,550) of patients age 65 years or older. Medicaid patients were statistically significantly less likely to receive short-term (less than 24 hours) medications and to undergo invasive cardiac procedures than patients covered by HMO and private insurance. They also had higher mortality rates (2.9% vs. 1.2%; adjusted odds ratio, 1.33; 95% CI, 1.08 to 1.63). Medications and invasive procedures were used to a similar extent in patients with Medicare and HMO or private insurance, and respective mortality rates were not significantly different (6.2% vs. 5.6%; adjusted odds ratio, 1.08; 95% CI, 0.99 to 1.18).Self-pay patients and patients without insurance were not assessed.NSTE ACS patients with Medicaid (but not Medicare) as the primary payer were less likely to receive evidence-based therapies and had worse outcomes than patients with HMO or private insurance as the primary payer. The causes of these treatment differences and solutions for narrowing the gaps in quality require further investigation.
In vitro analysis of allogeneic lymphocyte interaction. V. Identification and characterization of two components of allogeneic effect factor, one of which displays H-2-restricted helper activity and the other, T cell-growth factor activity.
Authors: T L Delovitch, J Watson, R Battistella, J F Harris, J Shaw, V Paetkau
Journal: The Journal of Experimental Medicine (1981)

An allogeneic effect factor (AEF) derived from mixed lymphocyte reaction (MLR) cultures of alloactivated A.SW (H-2s) responder T cells and irradiated A/WySn (H-2a) stimulator spleen cells helps an in vitro primary anti-erythrocyte plaque-forming cell PFC response of BALB/c nude spleen cels and also A/WySn but not A.SW T cell-depleted spleen cells. AEF activity is adsorbed by anti-Ik and anti-I-Ak but not by anti-I-Jk, anti-I-ECk, and anti-Is. Gel filtration of ACA 54 resolves AEF into two main components that which appear in the 50,000- to 70,000-mol wt (component I) and 30,000- to 35,000-mol wt (component II) regions, respectively. Component I has a mol wt of 68,000, elutes from DEAE-Sephacel at 0.05-0.1 M NaCl, and has an isoelectric point (pI) of 5.8. It helps A/WySn but not A.SW B cells and, therefore, is H-2 restricted. Component II is not H-2 restricted, because it helps both A.SW and A/WySn B cells. It also stimulates (a) the growth of a long-term cytotoxic cell line in vitro, (b) Con A-induced thymocyte mitogenesis, and (c) the generation of cytotoxic T cells. The latter three properties of component II are not shared by component I. In addition, component II elutes from DEAE-Sephacel at 0.15-0.2 M NaCl and has a pI of 4.3 and 4.9. Ia determinants and Ig VH, CH, L-chain, and idiotypic determinants are not present on either component I or component II. The properties of component II are identical to that of a T cell growth factor produced by Con A-stimulated spleen cells. It is suggested that the H-2-restricted component I of AEF might be an MLR-activated responder T cell-derived Ia alloantigen receptor.
American Society of Clinical Oncology Guidance Statement: The Cost of Cancer Care
Authors: Neal J. Meropol, Deborah Schrag, Thomas J. Smith, Therese M. Mulvey, Robert M. Langdon, Diane Blum, Peter A. Ubel, Lowell E. Schnipper
Journal: Journal of Clinical Oncology (2009)

Advances in early detection, prevention, and treatment have resulted in consistently falling cancer death rates in the United States. In parallel with these advances have come significant increases in the cost of cancer care. It is well established that the cost of health care (including cancer care) in the United States is growing more rapidly than the overall economy. In part, this is a result of the prices and rapid uptake of new agents and other technologies, including advances in imaging and therapeutic radiology. Conventional understanding suggests that high prices may reflect the costs and risks associated with the development, production, and marketing of new drugs and technologies, many of which are valued highly by physicians, patients, and payers. The increasing cost of cancer care impacts many stakeholders who play a role in a complex health care system. Our patients are the most vulnerable because they often experience uneven insurance coverage, leading to financial strain or even ruin. Other key groups include pharmaceutical manufacturers that pass along research, development, and marketing costs to the consumer; providers of cancer care who dispense increasingly expensive drugs and technologies; and the insurance industry, which ultimately passes costs to consumers. Increasingly, the economic burden of health care in general, and high-quality cancer care in particular, will be less and less affordable for an increasing number of Americans unless steps are taken to curb current trends. The American Society of Clinical Oncology (ASCO) is committed to improving cancer prevention, diagnosis, and treatment and eliminating disparities in cancer care through support of evidence-based and cost-effective practices. To address this goal, ASCO established a Cost of Care Task Force, which has developed this Guidance Statement on the Cost of Cancer Care. This Guidance Statement provides a concise overview of the economic issues facing stakeholders in the cancer community. It also recommends that the following steps be taken to address immediate needs: recognition that patient-physician discussions regarding the cost of care are an important component of high-quality care; the design of educational and support tools for oncology providers to promote effective communication about costs with patients; and the development of resources to help educate patients about the high cost of cancer care to help guide their decision making regarding treatment options. Looking to the future, this Guidance Statement also recommends that ASCO develop policy positions to address the underlying factors contributing to the increased cost of cancer care. Doing so will require a clear understanding of the factors that drive these costs, as well as potential modifications to the current cancer care system to ensure that all Americans have access to high-quality, cost-effective care.
Central Serotonergic Neurons Activate and Recruit Thermogenic Brown and Beige Fat and Regulate Glucose and Lipid Homeostasis
Authors: Jacob M. McGlashon, Michelle C. Gorecki, Amanda E. Kozlowski, Caitlin K. Thirnbeck, Kathleen R. Markan, Kirstie L. Leslie, Maya E. Kotas, Matthew J. Potthoff, George B. Richerson, Matthew P. Gillum
Journal: Cell Metabolism (2015)
How Important Is Bleomycin in the Adriamycin + Bleomycin + Vinblastine + Dacarbazine Regimen?
Authors: George P. Canellos, David Duggan, Jeffrey Johnson, Donna Niedzwiecki
Journal: Journal of Clinical Oncology (2004)

in reducing bony pain in metastatic prostate cancer. 3 It is also long-acting.A group of osteoporotic women who received a single dose of zoledronate (4 mg) demonstrated suppression of biochemical markers of bone resorption one year later. 4Most studies using zoledronate have reported a low incidence of asymptomatic hypocalcemia. 5,6][9] This report highlights the importance of diagnosing and treating vitamin D deficiency before initiating zoledronate therapy.Vitamin D deficiency has been well documented in elderly and inpatient populations and may have an incidence as high as 60%. 10,11In addition, proton pump inhibitors, which are being increasingly prescribed, limit the absorption of dietary calcium.As more patients with osteoporosis, skeletal metastases and hypercalcemia of malignancy are treated with intravenous bisphosphonates, the incidence of symptomatic hypocalcemia will likely increase, particularly in patients with underlying disorders of calcium and bone metabolism.This is particularly true in the case of zoledronate, which appears to be more potent and longer acting than older bisphosphonates.
OBSERVATIONS ON THE RÔLE OF THE RAT KIDNEY IN HYPERTENSION CAUSED BY DESOXYCORTICOSTERONE ACETATE
Authors: Sydney M. Friedman, Constance L. Friedman
Journal: The Journal of Experimental Medicine (1949)

Desoxycorticosterone acetate in pellet form was administered for 51 days to albino rats of the Sherman strain which also received 1 per cent saline as drinking water. Treatment was stopped in representative groups at 25, 37, and 51 days so that the regression of blood pressure and renal changes could be observed. It was noted that both the elevation in blood pressure during treatment and its reversal when treatment was stopped were closely correlated with corresponding changes in renal mass. In the time for which the process was studied it did not become irreversible. Removal of both kidneys from DCA-treated animals aggravated the hypertension, suggesting that the kidneys are actively concerned with the excretion and possible inactivation of the steroid.
Lymphocyte dynamics: caution in interpreting BAL numbers
Authors: R. Pabst, T. Tschernig
Journal: Thorax (1997)

In various allergic and inflammatory lung diseases the number and subset composition of lymphocytes in the bronchoalveolar lavage (BAL) fluid are taken as indicators of the state of the disease. The number of lymphocytes in the BAL fluid depends on three main parameters: (1) entry into the bronchoalveolar space from the different compartments of the lung, (2) persistence in the bronchoalveolar space which is modified by the rate of local proliferation and apoptosis, and (3) exit into the draining bronchial lymph node via the lymphatic system. In healthy individuals lymphocytes in the BAL fluid seem to be a stable pool: each day there is hardly any entry, local cell division or cell death and few lymphocytes emigrate from this compartment. In contrast, during inflammatory, toxic and allergic reactions all parameters can increase rapidly with more lymphocytes entering, proliferating and/or undergoing apoptosis locally. Very little is known about factors such as cytokines and chemokines which may regulate these parameters. When interpreting data on lymphocyte numbers in patients, lymphocyte dynamics in the bronchoalveolar space have to be considered, and in the future it may be possible to manipulate these lymphocyte fluxes for therapeutic purposes.
Skeletal muscle protein tyrosine phosphatase activity and tyrosine phosphatase 1B protein content are associated with insulin action and resistance.
Authors: J Kusari, K A Kenner, K I Suh, D E Hill, R R Henry
Journal: Journal of Clinical Investigation (1994)

Particulate and cytosolic protein tyrosine phosphatase (PTPase) activity was measured in skeletal muscle from 15 insulin-sensitive subjects and 5 insulin-resistant nondiabetic subjects, as well as 18 subjects with non-insulin-dependent diabetes mellitus (NIDDM). Approximately 90% of total PTPase activity resided in the particulate fraction. In comparison with lean nondiabetic subjects, particulate PTPase activity was reduced 21% (P < 0.05) and 22% (P < 0.005) in obese nondiabetic and NIDDM subjects, respectively. PTPase1B protein levels were likewise decreased by 38% in NIDDM subjects (P < 0.05). During hyperinsulinemic glucose clamps, glucose disposal rates (GDR) increased approximately sixfold in lean control and twofold in NIDDM subjects, while particulate PTPase activity did not change. However, a strong positive correlation (r = 0.64, P < 0.001) existed between particulate PTPase activity and insulin-stimulated GDR. In five obese NIDDM subjects, weight loss of approximately 10% body wt resulted in a significant and corresponding increase in both particulate PTPase activity and insulin-stimulated GDR. These findings indicate that skeletal muscle particulate PTPase activity and PTPase1B protein content reflect in vivo insulin sensitivity and are reduced in insulin resistant states. We conclude that skeletal muscle PTPase activity is involved in the chronic, but not acute regulation of insulin action, and that the decreased enzyme activity may have a role in the insulin resistance of obesity and NIDDM.
Themes of liver transplantation
Authors: Thomas E. Starzl, John J. Fung
Journal: Hepatology (2010)

Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as healthcare standards, the ethical, legal, equity, and the other humanism issues of Theme V have been resolved less conclusively than the medical-scientific problems of Themes I-IV.
Enzymatic Single-Chain Antibody Tagging
Authors: H.T. Ta, S. Prabhu, E. Leitner, F. Jia, D. von Elverfeldt, Katherine E. Jackson, T. Heidt, A.K.N. Nair, H. Pearce, C. von zur Muhlen, X. Wang, K. Peter, C.E. Hagemeyer
Journal: Circulation Research (2011)

Antibody-targeted delivery of imaging agents can enhance the sensitivity and accuracy of current imaging techniques. Similarly, homing of effector cells to disease sites increases the efficacy of regenerative cell therapy while reducing the number of cells required. Currently, targeting can be achieved via chemical conjugation to specific antibodies, which typically results in the loss of antibody functionality and in severe cell damage. An ideal conjugation technique should ensure retention of antigen-binding activity and functionality of the targeted biological component.To develop a biochemically robust, highly reproducible, and site-specific coupling method using the Staphylococcus aureus sortase A enzyme for the conjugation of a single-chain antibody (scFv) to nanoparticles and cells for molecular imaging and cell homing in cardiovascular diseases. This scFv specifically binds to activated platelets, which play a pivotal role in thrombosis, atherosclerosis, and inflammation.The conjugation procedure involves chemical and enzyme-mediated coupling steps. The scFv was successfully conjugated to iron oxide particles (contrast agents for magnetic resonance imaging) and to model cells. Conjugation efficiency ranged between 50% and 70%, and bioactivity of the scFv after coupling was preserved. The targeting of scFv-coupled cells and nanoparticles to activated platelets was strong and specific as demonstrated in in vitro static adhesion assays, in a flow chamber system, in mouse intravital microscopy, and in in vivo magnetic resonance imaging of mouse carotid arteries.This unique biotechnological approach provides a versatile and broadly applicable tool for procuring targeted regenerative cell therapy and targeted molecular imaging in cardiovascular and inflammatory diseases and beyond.
Signal transduction revisited: recent developments in angiotensin II signaling in the cardiovascular system
Authors: M van Bilsen
Journal: Cardiovascular Research (1997)

Time for primary review 31 days.

Two years have passed since the appearance of the focused issue on signal transduction (Cardiovascular Research, volume 30, issue 4, October 1995). In that issue a selection of topics related to cardiovascular signal transduction were highlighted. Since then a wealth of new information has deepened our insight into the factors that govern the activity of the different signal transduction pathways. Moreover, the importance of cross-talk between signal transduction pathways is being recognized and has, at the same time, made us aware of the complexity of the signal transduction network. Finally, new players in the field of cardiovascular signal transduction have emerged, the most striking example being the Stress-Activated Protein Kinases.

The purpose of this review is to summarize these new developments in this area of research. Considering the rate with which the various signal transduction pathways and their interrelationships are being deciphered the task of writing an update that pays tribute to all these new insights and developments is virtually impossible. Accordingly, as a major theme of this review the recent developments on angiotensin II-mediated signal transduction was chosen. This choice is not entirely arbitrary. In the October 1995 issue on cardiovascular signaling the role of angiotensin II (Ang II) was a main topic of various reviews already [1–3]. More importantly Ang II, either systemic or locally produced, is considered to play a pivotal role in cardiovascular adaptation. Signaling via this peptide growth factor involves various receptor subtypes and results in the activation of a variety of signal transduction cascades, which have been unravelled to a large extent over the past couple of years.

The major type of mechanical force to which the cardiac muscle is subjected is cyclic stretch. In contrast, the vascular endothelial cells face both cyclic stretch (pressure) and shear … 

* Corresponding author. Tel. +31-43-3881204; Fax +31-43-3671028; E-mail: marc.vanbilsen@fys.unimaas.nl