tbuckley/cabot-search huggingface dataset:
Abstract 1042: Balance between several phosphatases is crucial for statin- and ATP-induced depletion of nuclear pAkt in prostatic cancer cells
Authors: Aram Ghalali, Johan Högberg, Ulla Stenius
Journal: Cancer Research (2011)

Abstract We have previously shown that cholesterol-lowering drugs, statins, or extracellular ATP, induce a complex and coordinated response in insulin-stimulated non-small cell lung cancer cells (A549), leading to depletion of nuclear phosphorylated Akt (pAkt). The response involved activation of protein/lipid phosphatases PTEN, PHLPP1 and −2, PP2A and calcineurin (J Biol Chem, 285, 27900, 2010). As Akt might be critical for prostatic cancer (PC) development and statins may prevent aggressive PC the effects of statins and ATP on Akt signaling in PC cells was studied. It was found that atorvastatin in micromolar concentrations decreased constitutive levels of pAkt in DU145 and 22RV1 cells. The effect was associated with a decreased phosphorylation of downstream targets of pAkt. Furthermore, we found that insulin-induced pAkt was inhibited by atorvastatin. Our previous data indicated that PTEN and PHLPP are essential for depletion of nuclear pAkt. In line with this no down-regulation of nuclear Akt and its downstream targets was induced by statins in PTEN deficient LNCaP cells. However, the statin-induced down-regulation of nuclear Akt was restored when cells were transfected for PTEN. We also transfected PTEN deficient PC3 cells with PTEN. However, in this cell line PTEN transfection did not restore the capacity of statins to deplete nuclear pAkt. Instead, we found that in PC3 cells the PTEN transfection lowered levels of PHLPP2 and PHLPP1. When the cells were transfected for both PTEN and PHLPP2 the capacity of statins to deplete nuclear pAkt was restored in PC3 cells. The crosstalk between PHLPP and PTEN was further studied in LNCap, PC3, 22RV1 cells and it was found that increasing PTEN levels depressed the levels of PHLPP 1 and 2 and vice versa. The similar cross talk was also observed between PHLPP1 and 2. These data indicate that a balance between different phosphatases is essential for statin-induced depletion of nuclear Akt. This might be due to the fact that formation of complexes between Akt and different phosphatases is needed for the depletion of nuclear pAkt. Our data suggest that a well-controlled balance between essential phosphatases is needed for nuclear pAkt depletion. This balance seems disturbed in many prostate cancer cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1042. doi:10.1158/1538-7445.AM2011-1042
Biomarkers of lupus nephritis determined by serial urine proteomics
Authors: Xiaolan Zhang, Ming Jin, Haifeng Wu, Tibor Nadasdy, Gyongyi Nadasdy, Nathan Harris, Kari Green-Church, Haikady Nagaraja, Daniel J. Birmingham, Chack-Yung Yu, Lee A. Hebert, Brad H. Rovin
Journal: Kidney International (2008)
Charting a New Course for the Delivery of High-Quality Cancer Care
Authors: Patricia A. Ganz, Laura A. Levit
Journal: Journal of Clinical Oncology (2013)

Cancer is one of the most complicated diseases to diagnose and treat, requiring sophisticated pathological and imaging studies that are evaluated by multiple independent health care professionals. Most cancer therapies are expensive and toxic, and patients are treated with them for prolonged periods of time. When a person is told they have cancer, they often “shut down” and no longer hear anything further about the treatments that are being recommended. They enter a complex and fragmented cancer care system in which palliative care and psychosocial support are inadequately provided and hospice referral occurs far too late in the course of treatment. Many of these issues were identified in the transformative 1999 Institute of Medicine (IOM) report “Ensuring Quality Cancer Care,” which recommended structural changes to cancer care delivery and the development of a quality monitoring system. Unfortunately, many of the gaps in cancer care that the IOM identified more than a decade ago have been magnified today as a result of an explosion in knowledge of cancer biology, earlier diagnosis as a result of screening, more indications for adjuvant and multimodal therapies, and increasing numbers of long-term survivors. Cancer care accounts for a substantial proportion of health care expenditures, and the delivery system is being stressed by the aging of the population. The quality of cancer care in the United States is uneven, with few metrics to assess treatment outcomes among practitioners and in various clinical settings. With increasing demand for services, anticipated workforce shortages, and the rising costs of cancer care, delivery of affordable, accessible, high-quality cancer care in the future is in jeopardy. Given this situation, in 2012, an IOM committee composed of 17 individuals from diverse clinical backgrounds (medicine, nursing, oncology specialties, geriatrics, ethics, health outcomes research, palliative care, and patient advocacy) was asked to examine these issues and to make recommendations on how to improve the quality
Muscarinic-activated K+ current in bovine aortic endothelial cells.
Authors: S P Olesen, P F Davies, D E Clapham
Journal: Circulation Research (1988)

Isolated, cultured arterial endothelial cells express an acetylcholine (ACh)-activated K+ current in addition to an inward rectifier current whose conductance is unaffected by ACh. The cholinergic K+ current is specifically blocked by atropine (1 microM) and shows single saturation kinetics with ACh (half-maximal stimulation 51 nM ACh). Unlike the cardiac muscarinic receptor-gated K+ channel, its stimulation appears independent of a pertussis toxin-sensitive GTP-binding protein. Activation of the endothelial muscarinic K+ current resulting in hyperpolarization may represent an initial component of the vasodilatory effect of ACh.
Human neutrophils release serine proteases capable of activating prorenin.
Authors: V J Dzau, D Gonzalez, C Kaempfer, D Dubin, B U Wintroub
Journal: Circulation Research (1987)

Proteases from human neutrophils can generate angiotensin II directly from angiotensin I or angiotensinogen. We examined whether neutrophil protease also influences angiotensin formation by activating human prorenin (also called inactive renin). When incubated with partially purified plasma and amniotic prorenin, sonicates from 10(6) neutrophils resulted in 120 +/- 30% and 1,240 +/- 290% increase in renin activity, respectively. The pH optimum of neutrophil prorenin-activating enzyme(s) is 6.5-7.0, and the activity of the enzyme(s) is inhibited by a mixture of serine protease inhibitors but not by inhibitors of other proteases, suggesting that prorenin-activating enzyme(s) is a neutral serine protease(s). Stimulation of neutrophils by f-met-leu-phe in the presence of cytochalasin B resulted in release of prorenin-activating enzyme(s) in a dose-dependent fashion. We attempted to isolate prorenin-activating enzyme(s) from neutrophil granules using aprotinin-affinity and carboxymethyl cellulose chromatographies. Prorenin-activating enzyme(s) coeluted with cathepsin G and elastase activities. Prorenin activation was greatly inhibited by anticathepsin G antiserum. Purified cathepsin G activated prorenin in a dose-dependent fashion. Elastase probably also contributes to prorenin activation since purified elastase also activated human prorenin. We speculate that this neutrophilic angiotensin-generating system may play a role in the local generation and concentration of angiotensins by influencing multiple steps of the renin-angiotensin system.
The Complete Sports Medicine Book for Women
Authors: LETHA Y. Hunter
Journal: JAMA (1985)

In<i>The Complete Sports Medicine Book for Women</i>the authors discuss a gamut of issues relevant to the recreational female athlete, including nutritional tips, the use and abuse of drugs, specialized undergarments, exercise in the very young and very old, the effect of exercise on menstruation and pregnancy, and the treatment of some common athletic injuries. Although the authors have tried to write a text that explains medical issues in a form easily understood by the intended readers—female athletes, coaches, and trainers with no specialized medical background—at times they fail in this task, introducing terms and concepts difficult for the nonmedical person to understand. Furthermore, in their attempts to simplify complex issues, misconceptions occasionally surface. (For example, the authors' discussion of carbohydrate loading may be confusing to some.) Nonetheless, with these few exceptions, the book does provide much useful knowledge for women who desire to learn more about the medical
Increased Risk of Pancreatic Cancer in Melanoma-Prone Kindreds with<i>p16</i><sup>INK4</sup>Mutations
Authors: Alisa M. Goldstein, Mary C. Fraser, Jeffery P. Struewing, Christopher J. Hussussian, Koustubh Ranade, Deborah P. Zametkin, Laura S. Fontaine, Sara M. Organic, Nicholas C. Dracopoli, Wallace H. Clark, Margaret A. Tucker
Journal: New England Journal of Medicine (1995)

A gene on chromosome 9p, p16INK4, has been implicated in the pathogenesis of cutaneous malignant melanoma in 19 melanoma-prone families. In 10 of these kindreds mutations that impaired the function of the p16INK4 protein (p16M alleles) cosegregated with the disease. By contrast, in the other nine kindreds the mutation did not alter the function of p16INK4 (p16W alleles). We looked for differences in clinical and genetic epidemiologic features in these two groups of families.We compared the median ages at diagnosis of melanoma, number of melanomas, thickness of the tumors, and number of nevi in the kindreds. We estimated prospectively the risks of melanoma or other cancers in families followed for 6 to 18 years and the risks of other cancers since 1925 (the entire period) by comparing the number of cancer cases observed with the number expected.The risk of invasive melanoma was increased by a factor of 75 in kindreds with p16M alleles and a factor of 38 in kindreds with p16W alleles. Although this difference was not significant (P = 0.14), there was a striking difference in the risk of other tumors. In kindreds with p16M alleles, the risk of pancreatic cancer was increased by a factor of 13 in the prospective period (2 cases observed, 0.15 expected; standardized incidence ratio, 13.1; 95 percent confidence interval, 1.5 to 47.4) and by a factor of 22 in the entire period (7 cases observed, 0.32 expected; standardized incidence ratio, 21.8; 95 percent confidence interval, 8.7 to 44.8). In contrast, we found no cases of pancreatic cancer in kindred with p16W alleles.The development of pancreatic cancer in kindreds prone to melanoma may require a p16M mutation. Genetic factors, such as the kind of mutation found in p16INK4, may explain the inconsistent occurrence of other cancers in these kindreds.
Epithelial apoptosis in the initiation of lung fibrosis
Authors: B.D. Uhal
Journal: European Respiratory Journal (2003)

This work was supported by PHS HL‐45136, by the American Heart Association and by the MSU Foundation.

Apoptosis in the lung is a relatively new area of research that is receiving increasing attention. A growing body of evidence indicates that apoptosis is controlled in a tissue- and cell type-specific manner; for this reason, the regulation of apoptosis in specific cell types of the lung is currently an area of intensive research 1. This article provides evidence supporting the viewpoint that apoptosis of alveolar epithelial cells is a key event in the initiation of fibrotic lesions, and will discuss a working hypothesis to explain possible mechanisms by which epithelial apoptosis can lead to lung fibrogenesis.

Recent evidence implicates important roles for apoptosis in animal models of lung injury/repair or remodelling and in lung biopsies from patients with a variety of lung disorders. For example, apoptosis plays a critical role in postnatal lung development 2 and in the normal resolution of lung inflammation by the regulated removal of unneeded cells such as granulocytes, without the release of damaging histotoxins 3. Dexamethasone has been known for many years to induce apoptosis in some leukocyte subsets, and apoptosis is an important mechanism underlying the anti-inflammatory action of this and other glucocorticoids 4. Considerable literature now supports a role for apoptosis in the remodelling of lung tissue after acute lung injury, both for the clearance of excess epithelial stem cells after hyperplastic repair 5 and for the normal removal of excess mesenchymal cells from resolving lesions 6. Extensive apoptosis is found in the lungs of patients with idiopathic pulmonary fibrosis (IPF) 7, 8 and in animals of this disease 9, 10. Recent evidence also suggests a role for apoptosis in the tissue remodelling …
Physical Medicine and Rehabilitation
Authors: Henry H. Stonnington
Journal: JAMA (1979)

Frank Krusen established the first Department of Physical Medicine in Philadelphia in 1929. He and other pioneers, such as Miland Knapp, Howard Rusk, and Earl Elkins, created a specialty that emphasized rehabilitation of chronically disabled patients rather than treatment of disease as such.<sup>1,2</sup>Early neglect of disabling injuries and illnesses is far more costly both in money and in misery than an early aggressive program of rehabilitation designed to restore the person to the highest level of physical, economic, social, and emotional self-sufficiency.<sup>3</sup> Physical medicine and rehabilitation is in part a service specialty that helps physicians in other specialties to design patient programs that will relieve pain and contractures and improve strength, as well as to design prostheses, orthoses, ambulation aids, and adaptive equipment and programs for bowel, bladder, and skin care. It is also a primary care specialty for persons with chronic catastrophic disabilities. The specialist in
The Precordial Movements in Adults with Pulmonic Stenosis
Authors: JOHN H. HOLT, E. E. EDDLEMAN
Journal: Circulation (1967)

The precordial movements were studied in 24 adults with pulmonic stenosis. All patients were studied by cardiac catheterization. Normal kinetocardiographic criteria were applied to the patients with pulmonic stenosis. These provided a measure of the magnitude of atrial movements and relative amplitude and duration of movements associated with ventricular systole. Twenty-two patients had abnormal ventricular systolic movements by these criteria. These increased systolic movements are attributed to right ventricular overload. However, the location of these movements was frequently in areas generally considered as reflecting left ventricular activity. Possible explanations for this apparent paradox are discussed. There was a predictable relation between the motions associated with atrial contraction and the right ventricular pressure.
Cryosurgical ablation of atrioventricular nodal reentry: histologic localization of the proximal common pathway.
Authors: W L Holman, D B Hackel, J G Lease, M Ikeshita, J L Cox
Journal: Circulation (1988)

A method using cryosurgery has been previously described to selectively ablate atrioventricular nodal reentry tachycardia while preserving intact atrioventricular conduction. The purpose of the present study was to define the histologic features of the cryolesions in relationship to the specialized conduction system. In 12 adult dogs a series of nine discrete cryolesions was placed along the perimeter of the triangle of Koch while continuously monitoring the His bundle electrogram. All animals survived the operation and maintained intact atrioventricular conduction. At 14 weeks after surgery the hearts were sectioned and examined. In all 12 animals there was a confluent mass of dense fibrous tissue present in the lower atrial septum that was in immediate proximity to but did not involve the atrioventricular node-His bundle. The ablation of perinodal tissue with preservation of the specialized conduction system with the use of this cryosurgical technique was confirmed. It is likely that the cryoablated perinodal tissue represents the proximal common pathway of the circuit for atrioventricular nodal reentry tachycardia.
THE EFFECTS OF PHOSPHOPROTEINS ON ACID BALANCE IN NORMAL SUBECTS*
Authors: Edward J. Lennon, Jacob Lemann, Arnold S. Relman
Journal: Journal of Clinical Investigation (1962)

Identification and measurement of the dietary sources of fixed endogenous acid have been hampered by the chemical complexity of naturally occurring foods.Recent studies from this laboratory (1) have demonstrated the feasibility of identifying and quantitating the sources of fixed acid production when a chemically defined, synthetic diet is utilized and body composition remains approximately constant.With the special diet used in those studies, the processes resulting in net endogenous acid production in the steady state were identified as: a) the release of acid during the oxidation of neutral sulfur to inorganic sulfate, and b) the net production of organic acids from neutral foodstuffs.In addition, c) the data suggested that a third source of acid was related to the phosphorus content of the dietary protein, and it was proposed that acid was released during the oxidation of the cations neutralizing phosphate esters, or during the hydrolysis of phosphate diesters in the protein, or both.However, the amount of organic phosphorus in the basic diet was relatively small and analysis of its contributions to acid production was therefore limited.Accordingly, in the present experiments the postulated role of phosphorus was tested more critically by the administration of extra loads of the purified soy phosphoprotein used in the basic diet.The effects were compared with those of feeding equivalent loads of a more complex natu- ral protein (contained in cooked ground beef- steak).The data to be presented support our previous conclusions that a predictable amount of
HETEROZYGOSITY FOR *2 BUT NOT *17 CYP2C19 ALLELE EFFECTS PLATELET REACTIVITY MEASURED BY VERIFYNOW
Authors: Michael W. Cammarata, Joseph S. Rossi, Jayalalitha Dharmavaram, Christine M. Walko, Kenneth L. Muldrew, Karen E. Weck, Don A. Gabriel, George A. Stouffer
Journal: Journal of the American College of Cardiology (2011)
Screen for Asthma at School
Authors: Rebecca Voelker
Journal: JAMA (2000)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Selection of Patients and Operation for Revascularization Surgery
Authors: Arthur Vineberg
Journal: JAMA (1969)

In discussing the selection of patients and operations for relief of coronary artery disease, we shall attempt to correlate clinical, laboratory, and pathological information; to show the evolution from a single internal mammary artery implant to our present concept of implant or implants combined with epicardiectomy and free omental graft; and to outline the place of multiple implants with and without free omental grafts, particularly in relation to previous myocardial infarctions. In our experience with well over 400 revascularization operations, followed up to 17 years, 75% of our patients have suffered from one to six previous myocardial infarctions. In addition, since 1962, patients with large left ventricles and ventricles in a state of failure have been successfully treated. In fact, 25% of our patients had chronic left ventricular failure at the time of operation, and 65% of these have returned to the community, no longer with this condition. The point
Estimating Incidence of HIV Infection in Uganda
Authors: Michael Westerhaus
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal